@article{
 title = {Fluidic shaping of optical components},
 type = {article},
 year = {2021},
 volume = {1},
 publisher = {Cambridge University Press (CUP)},
 id = {5dac6cc3-b188-3a2a-a83e-5b84a51644f6},
 created = {2021-10-29T17:39:41.205Z},
 accessed = {2021-10-29},
 file_attached = {true},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2021-10-29T18:31:51.579Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
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 abstract = {    Current methods for fabricating lenses rely on mechanical processing of the lens or mould, such as grinding, machining and polishing. The complexity of these fabrication processes and the required specialized equipment prohibit rapid prototyping of optical components. This work presents a simple method, based on free-energy minimization of liquid volumes, which allows us to quickly shape curable liquids into a wide range of spherical and aspherical optical components, without the need for any mechanical processing. After the desired shape is obtained, the liquid can be cured to produce a solid object with nanometric surface quality. We provide a theoretical model that accurately predicts the shape of the optical components, and demonstrate rapid fabrication of all types of spherical lenses (convex, concave, meniscus), cylindrical lenses, bifocal lenses, toroidal lenses, doublet lenses and aspheric lenses. The method is inexpensive and can be implemented using a variety of curable liquids with different optical and mechanical properties. In addition, the method is scale invariant and can be used to produce even very large optical components, without a significant increase in fabrication time. We believe that the ability to easily and rapidly create optical components, without the need for complex and expensive infrastructure, will provide researchers with new affordable tools for fabricating and testing optical designs.},
 bibtype = {article},
 author = {Frumkin, Valeri and Bercovici, Moran},
 journal = {Flow}
}

Current methods for fabricating lenses rely on mechanical processing of the lens or mould, such as grinding, machining and polishing. The complexity of these fabrication processes and the required specialized equipment prohibit rapid prototyping of optical components. This work presents a simple method, based on free-energy minimization of liquid volumes, which allows us to quickly shape curable liquids into a wide range of spherical and aspherical optical components, without the need for any mechanical processing. After the desired shape is obtained, the liquid can be cured to produce a solid object with nanometric surface quality. We provide a theoretical model that accurately predicts the shape of the optical components, and demonstrate rapid fabrication of all types of spherical lenses (convex, concave, meniscus), cylindrical lenses, bifocal lenses, toroidal lenses, doublet lenses and aspheric lenses. The method is inexpensive and can be implemented using a variety of curable liquids with different optical and mechanical properties. In addition, the method is scale invariant and can be used to produce even very large optical components, without a significant increase in fabrication time. We believe that the ability to easily and rapidly create optical components, without the need for complex and expensive infrastructure, will provide researchers with new affordable tools for fabricating and testing optical designs.

@article{
 title = {Biointegrated Fluidic Milling},
 type = {article},
 year = {2021},
 volume = {6},
 month = {2},
 day = {16},
 id = {931f93c2-5b3d-3761-a02f-9f726bc38427},
 created = {2021-10-29T18:24:28.584Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2021-10-30T20:28:10.385Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Widerker, Daniel and Paratore, Federico and Bercovici, Moran and Kaigala, Govind},
 doi = {10.1002/admt.202000843},
 journal = {Advanced Materials Technologies},
 number = {2}
}

@article{
 title = {Microscale Hydrodynamic Cloaking and Shielding via Electro-Osmosis},
 type = {article},
 year = {2021},
 volume = {126},
 month = {5},
 day = {6},
 id = {52ad0421-9956-3a78-9528-6688d8e48ec5},
 created = {2021-10-29T18:29:53.542Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2021-10-30T20:26:26.782Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Boyko, Evgeniy and Bacheva, Vesna and Eigenbrod, Michael and Paratore, Federico and Gat, Amir D. and Hardt, Steffen and Bercovici, Moran},
 doi = {10.1103/PhysRevLett.126.184502},
 journal = {Physical Review Letters},
 number = {18}
}

@article{
 title = {Fabrication of diffractive optical elements by programmable thermocapillary shaping of thin liquid films},
 type = {article},
 year = {2021},
 month = {8},
 day = {31},
 id = {e0115d66-b5fa-3401-8503-26431edcfca0},
 created = {2021-10-29T18:30:35.988Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2021-10-30T20:26:26.768Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Diffractive optical elements (DOEs) enable precise manipulation of wavefronts and are widely used in a variety of optical systems. However, their fabrication relies on lithography or high precision machining processes that are long, expensive, and infrastructure-heavy. We here present a one-step rapid fabrication method that leverages the thermocapillary effect to shape thin liquid films into useful DOEs with sub-nanometeric surface roughness. Our system consists of a projection system, which illuminates any desired pattern onto the bottom of a fluidic chamber patterned with heat-absorbing pads. The heat induces surface tension gradients in the polymer-air interface, resulting in the polymer film deformation. The polymer is then photocured to yield a solid device. We developed a theoretical model that provides the required projection pattern to achieve a desired topography. Based on this model, we demonstrate the fabrication of several DOEs, including phase masks for extended depth of field imaging, and for 3D localization microscopy. Fabrication is completed in less than five minutes and requires no post-processing.},
 bibtype = {article},
 author = {Eshel, Ran and Frumkin, Valeri and Nice, Matan and Luria, Omer and Ferdman, Boris and Opatovski, Nadav and Gommed, Khaled and Shusteff, Maxim and Shechtman, Yoav and Bercovici, Moran}
}

Diffractive optical elements (DOEs) enable precise manipulation of wavefronts and are widely used in a variety of optical systems. However, their fabrication relies on lithography or high precision machining processes that are long, expensive, and infrastructure-heavy. We here present a one-step rapid fabrication method that leverages the thermocapillary effect to shape thin liquid films into useful DOEs with sub-nanometeric surface roughness. Our system consists of a projection system, which illuminates any desired pattern onto the bottom of a fluidic chamber patterned with heat-absorbing pads. The heat induces surface tension gradients in the polymer-air interface, resulting in the polymer film deformation. The polymer is then photocured to yield a solid device. We developed a theoretical model that provides the required projection pattern to achieve a desired topography. Based on this model, we demonstrate the fabrication of several DOEs, including phase masks for extended depth of field imaging, and for 3D localization microscopy. Fabrication is completed in less than five minutes and requires no post-processing.

@article{
 title = {Shaping liquid films by dielectrophoresis},
 type = {article},
 year = {2021},
 month = {2},
 day = {18},
 id = {71de195d-4735-3a25-a7e3-e642c71ecacb},
 created = {2021-10-29T18:31:02.717Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2021-10-30T20:26:26.952Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {We present a theoretical model and experimental demonstration of thin liquid film deformations due to a dielectric force distribution established by surface electrodes. We model the spatial electric field produced by a pair of parallel electrodes and use it to evaluate the stress on the interface through Maxwell stresses. By coupling this force with the Young-Laplace equation, we obtain the deformation of the interface. To validate our theory, we design an experimental setup which uses microfabricated electrodes to achieve spatial dielectrophoretic actuation of a thin liquid film, while providing measurements of microscale deformations through digital holographic microscopy. We characterize the deformation as a function of the electrode-pair geometry and film thickness, showing very good agreement with the model. Based on the insights from the characterization of the system, we pattern conductive lines of electrode pairs on the surface of a microfluidic chamber and demonstrate the ability to produce complex two-dimensional deformations. The films can remain in liquid form and be dynamically modulated between different configurations or polymerized to create solid structures with high surface quality.},
 bibtype = {article},
 author = {Gabay, Israel and Paratore, Federico and Boyko, Evgeniy and Ramos, Antonio and Gat, Amir D. and Bercovici, Moran}
}

We present a theoretical model and experimental demonstration of thin liquid film deformations due to a dielectric force distribution established by surface electrodes. We model the spatial electric field produced by a pair of parallel electrodes and use it to evaluate the stress on the interface through Maxwell stresses. By coupling this force with the Young-Laplace equation, we obtain the deformation of the interface. To validate our theory, we design an experimental setup which uses microfabricated electrodes to achieve spatial dielectrophoretic actuation of a thin liquid film, while providing measurements of microscale deformations through digital holographic microscopy. We characterize the deformation as a function of the electrode-pair geometry and film thickness, showing very good agreement with the model. Based on the insights from the characterization of the system, we pattern conductive lines of electrode pairs on the surface of a microfluidic chamber and demonstrate the ability to produce complex two-dimensional deformations. The films can remain in liquid form and be dynamically modulated between different configurations or polymerized to create solid structures with high surface quality.

@article{
 title = {Nonuniform Electro-osmotic Flow Drives Fluid-Structure Instability},
 type = {article},
 year = {2020},
 pages = {24501},
 volume = {124},
 publisher = {APS},
 id = {17e7e823-0d83-3013-a220-b3415bf7c7c3},
 created = {2020-02-13T21:38:09.492Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-02-13T21:39:25.571Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 source_type = {article},
 private_publication = {false},
 bibtype = {article},
 author = {Boyko, Evgeniy and Eshel, Ran and Gat, Amir D and Bercovici, Moran},
 journal = {Physical Review Letters},
 number = {2}
}

@article{
 title = {Electro-osmotic flow enhancement over superhydrophobic surfaces},
 type = {article},
 year = {2020},
 pages = {053701},
 volume = {5},
 websites = {https://journals.aps.org/prfluids/abstract/10.1103/PhysRevFluids.5.053701},
 month = {5},
 publisher = {American Physical Society},
 day = {1},
 id = {4a7cf1e5-90a2-30b0-b884-a4694bc368aa},
 created = {2020-10-03T07:33:55.815Z},
 accessed = {2020-10-03},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-10-03T09:21:38.587Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 folder_uuids = {e291ede5-6371-4e5f-beba-651d9ca32825},
 private_publication = {false},
 abstract = {Electro-osmotic flow is a well-established and efficient method for driving microchannel flows that relies on the interaction of an externally applied electric field with charge arising at the interface between the liquid and the channel walls. However, its relatively low velocities together with its dependence on the pH of the liquid severely limit its utility. Here we experimentally demonstrate fast electro-osmotic flow over microstructured superhydrophobic surfaces. By suspending the electrolyte in a Cassie-Baxter state over hierarchical surfaces, we create stable gas-liquid interfaces on which we induce charge through a gate electrode. We provide a detailed investigation and characterization of the electro-osmotic velocity as a function of the surface geometry by utilizing particle tracking velocimetry in a microfluidic device and show that the resulting electro-osmotic velocity scales with the ratio of slip length to double-layer thickness. Compared to no-slip surfaces, we demonstrate an order of magnitude enhancement in velocity and complete pH independence, enabling wider utility of electro-osmotic flow in manipulation of microscale flows.},
 bibtype = {article},
 author = {Dehe, Sebastian and Rofman, Baruch and Bercovici, Moran and Hardt, Steffen},
 doi = {10.1103/PhysRevFluids.5.053701},
 journal = {Physical Review Fluids},
 number = {5}
}

Electro-osmotic flow is a well-established and efficient method for driving microchannel flows that relies on the interaction of an externally applied electric field with charge arising at the interface between the liquid and the channel walls. However, its relatively low velocities together with its dependence on the pH of the liquid severely limit its utility. Here we experimentally demonstrate fast electro-osmotic flow over microstructured superhydrophobic surfaces. By suspending the electrolyte in a Cassie-Baxter state over hierarchical surfaces, we create stable gas-liquid interfaces on which we induce charge through a gate electrode. We provide a detailed investigation and characterization of the electro-osmotic velocity as a function of the surface geometry by utilizing particle tracking velocimetry in a microfluidic device and show that the resulting electro-osmotic velocity scales with the ratio of slip length to double-layer thickness. Compared to no-slip surfaces, we demonstrate an order of magnitude enhancement in velocity and complete pH independence, enabling wider utility of electro-osmotic flow in manipulation of microscale flows.

@article{
 title = {Tunable Bidirectional Electroosmotic Flow for Diffusion‐Based Separations},
 type = {article},
 year = {2020},
 keywords = {diffusion-based separations,diffusivity,electrokinetics,fractionation,microfluidics},
 pages = {12994-12999},
 volume = {132},
 websites = {https://onlinelibrary.wiley.com/doi/10.1002/ange.201916699},
 month = {7},
 publisher = {Wiley-Blackwell},
 day = {27},
 id = {27bfcecf-6c01-3f43-9f58-a13e62ca8d1c},
 created = {2020-10-03T07:34:33.043Z},
 accessed = {2020-10-03},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-10-03T09:21:38.581Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 folder_uuids = {e291ede5-6371-4e5f-beba-651d9ca32825},
 private_publication = {false},
 abstract = {We present a new concept for on-chip separation that leverages bidirectional flow, to tune the dispersion regime of molecules and particles. The system can be configured so that low diffusivity species experience a ballistic transport regime and are advected through the chamber, whereas high diffusivity species experience a diffusion dominated regime with zero average velocity and are retained in the chamber. We detail the means of achieving bidirectional electroosmotic flow using an array of alternating current (AC) field-effect electrodes, experimentally demonstrate the separation of particles and antibodies from dyes, and present a theoretical analysis of the system, providing engineering guidelines for its design and operation.},
 bibtype = {article},
 author = {Bacheva, Vesna and Paratore, Federico and Rubin, Shimon and Kaigala, Govind V. and Bercovici, Moran},
 doi = {10.1002/ange.201916699},
 journal = {Angewandte Chemie},
 number = {31}
}

We present a new concept for on-chip separation that leverages bidirectional flow, to tune the dispersion regime of molecules and particles. The system can be configured so that low diffusivity species experience a ballistic transport regime and are advected through the chamber, whereas high diffusivity species experience a diffusion dominated regime with zero average velocity and are retained in the chamber. We detail the means of achieving bidirectional electroosmotic flow using an array of alternating current (AC) field-effect electrodes, experimentally demonstrate the separation of particles and antibodies from dyes, and present a theoretical analysis of the system, providing engineering guidelines for its design and operation.

@article{
 title = {Intermediate States of Wetting on Hierarchical Superhydrophobic Surfaces},
 type = {article},
 year = {2020},
 pages = {5517-5523},
 volume = {36},
 websites = {https://pubs.acs.org/doi/abs/10.1021/acs.langmuir.0c00499},
 month = {5},
 publisher = {American Chemical Society},
 day = {26},
 id = {6c4f3f49-d754-3323-8acd-d7f1e3027c92},
 created = {2020-10-03T07:34:46.515Z},
 accessed = {2020-10-03},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-10-03T09:21:38.767Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 folder_uuids = {e291ede5-6371-4e5f-beba-651d9ca32825},
 private_publication = {false},
 abstract = {Wetting transition on superhydrophobic surfaces is commonly described as an abrupt jump between two stable states - either from Cassie to Wenzel for nonhierarchical surfaces or from Cassie to nano-Cassie on hierarchical surfaces. We here experimentally study the electrowetting of hierarchical superhydrophobic surfaces composed of multiple length scales by imaging the light reflections from the gas-liquid interface. We present the existence of a continuous set of intermediate states of wetting through which the gas-liquid interface transitions under a continuously increasing external forcing. This transition is partially reversible and is limited only by localized Cassie to Wenzel transitions at nanodefects in the structure. In addition, we show that even a surface containing many localized wetted regions can still exhibit extremely low contact angle hysteresis, thus remaining useful for many heat transfer and self-cleaning applications. Expanding the classical definition of the Cassie state in the context of hierarchical surfaces, from a single state to a continuum of metastable states ranging from the centimeter to the nanometer scale, is important for a better description of the slip properties of superhydrophobic surfaces and provides new considerations for their effective design.},
 bibtype = {article},
 author = {Rofman, Baruch and Dehe, Sebastian and Frumkin, Valeri and Hardt, Steffen and Bercovici, Moran},
 doi = {10.1021/acs.langmuir.0c00499},
 journal = {Langmuir},
 number = {20}
}

Wetting transition on superhydrophobic surfaces is commonly described as an abrupt jump between two stable states - either from Cassie to Wenzel for nonhierarchical surfaces or from Cassie to nano-Cassie on hierarchical surfaces. We here experimentally study the electrowetting of hierarchical superhydrophobic surfaces composed of multiple length scales by imaging the light reflections from the gas-liquid interface. We present the existence of a continuous set of intermediate states of wetting through which the gas-liquid interface transitions under a continuously increasing external forcing. This transition is partially reversible and is limited only by localized Cassie to Wenzel transitions at nanodefects in the structure. In addition, we show that even a surface containing many localized wetted regions can still exhibit extremely low contact angle hysteresis, thus remaining useful for many heat transfer and self-cleaning applications. Expanding the classical definition of the Cassie state in the context of hierarchical surfaces, from a single state to a continuum of metastable states ranging from the centimeter to the nanometer scale, is important for a better description of the slip properties of superhydrophobic surfaces and provides new considerations for their effective design.

@article{
 title = {Interfacial instability of thin films in soft microfluidic configurations actuated by electro-osmotic flow},
 type = {article},
 year = {2020},
 pages = {104201},
 volume = {5},
 websites = {https://link.aps.org/doi/10.1103/PhysRevFluids.5.104201},
 month = {10},
 publisher = {American Physical Society},
 day = {1},
 id = {7180e58e-5faa-3ef6-bc6f-5ec2c22f333c},
 created = {2020-10-03T09:25:48.371Z},
 accessed = {2020-10-03},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-10-03T09:27:31.269Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Boyko, Evgeniy and Ilssar, Dotan and Bercovici, Moran and Gat, Amir D.},
 doi = {10.1103/PhysRevFluids.5.104201},
 journal = {Physical Review Fluids},
 number = {10}
}

@article{
 title = {Microfluidic device for coupling isotachophoretic sample focusing with nanopore single-molecule sensing},
 type = {article},
 year = {2020},
 pages = {17805-17811},
 volume = {12},
 websites = {https://pubs-rsc-org.ezlibrary.technion.ac.il/en/content/articlehtml/2020/nr/d0nr05000h,https://pubs-rsc-org.ezlibrary.technion.ac.il/en/content/articlelanding/2020/nr/d0nr05000h},
 month = {9},
 publisher = {NLM (Medline)},
 day = {14},
 id = {aa39955d-9baf-35b2-a8fa-c74d674ddce4},
 created = {2020-10-03T09:27:09.643Z},
 accessed = {2020-10-03},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-10-03T09:27:31.279Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Solid-state nanopores (NPs) are label-free single-molecule sensors, capable of performing highly sensitive assays from a small number of biomolecule translocation events. However, single-molecule sensing is challenging at extremely low analyte concentrations due to the limited flux of analytes to the sensing volume. This leads to a low event rate and increases the overall assay time. In this work, we present a method to enhance the event rate at low analyte concentrations by using isotachophoresis (ITP) to focus and deliver analytes to a nanopore sensor. Central to this method is a device capable of performing ITP focusing directly on a solid-state NP chip, while preventing the focusing electric field from damaging the nanopore membrane. We discuss considerations and trade-offs related to the design of the focusing channel, the ITP electrolyte system and electrical decoupling between the focusing and sensing modes. Finally, we demonstrate an integrated device wherein the concentration enhancement due to ITP focusing leads to an increase in event rate of >300-fold in the ITP-NP device as compared to the NP-only case.},
 bibtype = {article},
 author = {Spitzberg, Joshua D. and van Kooten, Xander F. and Bercovici, Moran and Meller, Amit},
 doi = {10.1039/d0nr05000h},
 journal = {Nanoscale},
 number = {34}
}

Solid-state nanopores (NPs) are label-free single-molecule sensors, capable of performing highly sensitive assays from a small number of biomolecule translocation events. However, single-molecule sensing is challenging at extremely low analyte concentrations due to the limited flux of analytes to the sensing volume. This leads to a low event rate and increases the overall assay time. In this work, we present a method to enhance the event rate at low analyte concentrations by using isotachophoresis (ITP) to focus and deliver analytes to a nanopore sensor. Central to this method is a device capable of performing ITP focusing directly on a solid-state NP chip, while preventing the focusing electric field from damaging the nanopore membrane. We discuss considerations and trade-offs related to the design of the focusing channel, the ITP electrolyte system and electrical decoupling between the focusing and sensing modes. Finally, we demonstrate an integrated device wherein the concentration enhancement due to ITP focusing leads to an increase in event rate of >300-fold in the ITP-NP device as compared to the NP-only case.

@article{
 title = {Microscopic scan-free surface profiling over extended axial ranges by point-spread-function engineering},
 type = {article},
 year = {2020},
 volume = {6},
 id = {2ad3f076-d21c-3cdc-b2e4-35e8c0690921},
 created = {2020-11-07T23:59:00.000Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-11-11T12:12:00.433Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {true},
 abstract = {Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). The shape of a surface, i.e., its topography, influences many functional properties of a material; hence, characterization is critical in a wide variety of applications. Two notable challenges are profiling temporally changing structures, which requires high-speed acquisition, and capturing geometries with large axial steps. Here, we leverage point-spread-function engineering for scan-free, dynamic, microsurface profiling. The presented method is robust to axial steps and acquires full fields of view at camera-limited framerates. We present two approaches for implementation: fluorescence-based and label-free surface profiling, demonstrating the applicability to a variety of sample geometries and surface types.},
 bibtype = {article},
 author = {Gordon-Soffer, R. and Weiss, L.E. and Eshel, R. and Ferdman, B. and Nehme, E. and Bercovici, M. and Shechtman, Y.},
 doi = {10.1126/sciadv.abc0332},
 journal = {Science advances},
 number = {44}
}

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). The shape of a surface, i.e., its topography, influences many functional properties of a material; hence, characterization is critical in a wide variety of applications. Two notable challenges are profiling temporally changing structures, which requires high-speed acquisition, and capturing geometries with large axial steps. Here, we leverage point-spread-function engineering for scan-free, dynamic, microsurface profiling. The presented method is robust to axial steps and acquires full fields of view at camera-limited framerates. We present two approaches for implementation: fluorescence-based and label-free surface profiling, demonstrating the applicability to a variety of sample geometries and surface types.

@article{
 title = {Erratum: Nanoliter Cell Culture Array with Tunable Chemical Gradients (Analytical Chemistry (2018) 90 (7480-7488) DOI: 10.1021/acs.analchem.8b01017)},
 type = {article},
 year = {2020},
 volume = {92},
 id = {4cd8d603-666a-397d-af08-e4160ec1010d},
 created = {2020-02-05T23:59:00.000Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2021-03-06T08:38:25.756Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {true},
 abstract = {© 2020 American Chemical Society. All rights reserved. We found some errors and typographical errors related to the analytical model that we would like to correct. CORRECTIONS TO THE MANUSCRIPT TEXT On page 7483, in the equation following line 5, Pe should be replaced with Pea. This was a typographical error. On page 7483, the equation following line 10 should instead be [Equation presented] This was an arithmetic error when adding the ghost sources. We note that the analytical model derivation and related plots in Figures 2 and 3 remain unchanged. CORRECTIONS TO THE SUPPORTING INFORMATION In the last equation on page S-4 and in the first equation on page S-5, all of the Pe terms should be replaced with Pea. This was a typographical error. Page S-5, the final infinite sum equation should be [Equation presented] This was an arithmetic error made when adding the ghost sources.},
 bibtype = {article},
 author = {Avesar, J. and Blinder, Y. and Aktin, H. and Szklanny, A. and Rosenfeld, D. and Savir, Y. and Bercovici, M. and Levenberg, S.},
 doi = {10.1021/acs.analchem.0c00063},
 journal = {Analytical Chemistry},
 number = {3}
}

© 2020 American Chemical Society. All rights reserved. We found some errors and typographical errors related to the analytical model that we would like to correct. CORRECTIONS TO THE MANUSCRIPT TEXT On page 7483, in the equation following line 5, Pe should be replaced with Pea. This was a typographical error. On page 7483, the equation following line 10 should instead be [Equation presented] This was an arithmetic error when adding the ghost sources. We note that the analytical model derivation and related plots in Figures 2 and 3 remain unchanged. CORRECTIONS TO THE SUPPORTING INFORMATION In the last equation on page S-4 and in the first equation on page S-5, all of the Pe terms should be replaced with Pea. This was a typographical error. Page S-5, the final infinite sum equation should be [Equation presented] This was an arithmetic error made when adding the ghost sources.

@article{
 title = {Elastohydrodynamics of a pre-stretched finite elastic sheet lubricated by a thin viscous film with application to microfluidic soft actuators},
 type = {article},
 year = {2019},
 pages = {732-752},
 volume = {862},
 websites = {https://www.cambridge.org/core/product/identifier/S0022112018009679/type/journal_article},
 publisher = {Cambridge University Press},
 id = {07ab1a81-c04a-375a-b893-a6a287ab83ab},
 created = {2019-01-20T06:08:16.490Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.803Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {boyko2019elastohydrodynamics},
 source_type = {article},
 private_publication = {false},
 abstract = {<p>The interaction of a thin viscous film with an elastic sheet results in coupling of pressure and deformation, which can be utilized as an actuation mechanism for surface deformations in a wide range of applications, including microfluidics, optics and soft robotics. Implementation of such configurations inherently takes place over finite domains and often requires some pre-stretching of the sheet. Under the assumptions of strong pre-stretching and small deformations of the lubricated elastic sheet, we use the linearized Reynolds and Föppl–von Kármán equations to derive closed-form analytical solutions describing the deformation in a finite domain due to external forces, accounting for both bending and tension effects. We provide a closed-form solution for the case of a square-shaped actuation region and present the effect of pre-stretching on the dynamics of the deformation. We further present the dependence of the deformation magnitude and time scale on the spatial wavenumber, as well as the transition between stretching- and bending-dominant regimes. We also demonstrate the effect of spatial discretization of the forcing (representing practical actuation elements) on the achievable resolution of the deformation. Extending the problem to an axisymmetric domain, we investigate the effects arising from nonlinearity of the Reynolds and Föppl–von Kármán equations and present the deformation behaviour as it becomes comparable to the initial film thickness and dependent on the induced tension. These results set the theoretical foundation for implementation of microfluidic soft actuators based on elastohydrodynanmics.</p>},
 bibtype = {article},
 author = {Boyko, Evgeniy and Eshel, Ran and Gommed, Khaled and Gat, Amir D. and Bercovici, Moran},
 doi = {10.1017/jfm.2018.967},
 journal = {Journal of Fluid Mechanics}
}

The interaction of a thin viscous film with an elastic sheet results in coupling of pressure and deformation, which can be utilized as an actuation mechanism for surface deformations in a wide range of applications, including microfluidics, optics and soft robotics. Implementation of such configurations inherently takes place over finite domains and often requires some pre-stretching of the sheet. Under the assumptions of strong pre-stretching and small deformations of the lubricated elastic sheet, we use the linearized Reynolds and Föppl–von Kármán equations to derive closed-form analytical solutions describing the deformation in a finite domain due to external forces, accounting for both bending and tension effects. We provide a closed-form solution for the case of a square-shaped actuation region and present the effect of pre-stretching on the dynamics of the deformation. We further present the dependence of the deformation magnitude and time scale on the spatial wavenumber, as well as the transition between stretching- and bending-dominant regimes. We also demonstrate the effect of spatial discretization of the forcing (representing practical actuation elements) on the achievable resolution of the deformation. Extending the problem to an axisymmetric domain, we investigate the effects arising from nonlinearity of the Reynolds and Föppl–von Kármán equations and present the deformation behaviour as it becomes comparable to the initial film thickness and dependent on the induced tension. These results set the theoretical foundation for implementation of microfluidic soft actuators based on elastohydrodynanmics.

@article{
 title = {Dynamic control of capillary flow in porous media by electroosmotic pumping},
 type = {article},
 year = {2019},
 websites = {http://xlink.rsc.org/?DOI=C8LC01077C},
 publisher = {Royal Society of Chemistry},
 id = {c6d5f6f1-dbe9-36f5-aabd-93e1c58f88e8},
 created = {2019-01-20T06:08:16.841Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
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 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {rosenfeld2019dynamic},
 source_type = {article},
 private_publication = {false},
 abstract = {Microfluidic paper-based analytical devices (μPADs) rely on capillary flow to achieve filling, mixing and delivery of liquids. We investigate the use of electroosmotic (EO) pumping as a mechanism for dynamic control of capillary flow in paper-based devices. The applied voltage can accelerate or decelerate the baseline capillary-driven velocity, as well as be used to create a tunable valve that reversibly switches the flow on and off in an electrically controlled manner. The method relies on simple fabrication and allows repeated actuation, providing a high degree of flexibility for automation of liquid delivery. We adapt the Lucas–Washburn model to account for EO pumping and provide an experimentally validated analytical model for the distance penetrated by the liquid as a function of time and the applied voltage. We show that the EO-pump can reduce filling time by 6.5-fold for channels spanning several cm in length, relative to capillary filling alone. We demonstrate the utilization of the EO-pump for a tunable and dynamic flow control that accelerates, decelerates and stops the flow on demand. Finally, we present the use of the EO-pump for fluid flow sequencing on a paper-based device.},
 bibtype = {article},
 author = {Rosenfeld, Tally and Bercovici, Moran},
 doi = {10.1039/C8LC01077C},
 journal = {Lab on a Chip},
 keywords = {Fluid-structure}
}

Microfluidic paper-based analytical devices (μPADs) rely on capillary flow to achieve filling, mixing and delivery of liquids. We investigate the use of electroosmotic (EO) pumping as a mechanism for dynamic control of capillary flow in paper-based devices. The applied voltage can accelerate or decelerate the baseline capillary-driven velocity, as well as be used to create a tunable valve that reversibly switches the flow on and off in an electrically controlled manner. The method relies on simple fabrication and allows repeated actuation, providing a high degree of flexibility for automation of liquid delivery. We adapt the Lucas–Washburn model to account for EO pumping and provide an experimentally validated analytical model for the distance penetrated by the liquid as a function of time and the applied voltage. We show that the EO-pump can reduce filling time by 6.5-fold for channels spanning several cm in length, relative to capillary filling alone. We demonstrate the utilization of the EO-pump for a tunable and dynamic flow control that accelerates, decelerates and stops the flow on demand. Finally, we present the use of the EO-pump for fluid flow sequencing on a paper-based device.

@article{
 title = {Dynamic microscale flow patterning using electrical modulation of zeta potential.},
 type = {article},
 year = {2019},
 keywords = {Hele–Shaw cell,electrokinetics,electroosmotic flow,microfluidics,viscous flow},
 pages = {10258-10263},
 volume = {116},
 websites = {http://www.ncbi.nlm.nih.gov/pubmed/31061121},
 month = {5},
 publisher = {National Academy of Sciences},
 day = {6},
 id = {ca5e41be-95d9-3222-953f-278e389a38d8},
 created = {2019-05-22T05:25:29.482Z},
 accessed = {2019-05-22},
 file_attached = {true},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-06-19T15:46:06.498Z},
 read = {true},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {The ability to move fluids at the microscale is at the core of many scientific and technological advancements. Despite its importance, microscale flow control remains highly limited by the use of discrete channels and mechanical valves, and relies on fixed geometries. Here we present an alternative mechanism that leverages localized field-effect electroosmosis to create dynamic flow patterns, allowing fluid manipulation without the use of physical walls. We control a set of gate electrodes embedded in the floor of a fluidic chamber using an ac voltage in sync with an external electric field, creating nonuniform electroosmotic flow distributions. These give rise to a pressure field that drives the flow throughout the chamber. We demonstrate a range of unique flow patterns that can be achieved, including regions of recirculating flow surrounded by quiescent fluid and volumes of complete stagnation within a moving fluid. We also demonstrate the interaction of multiple gate electrodes with an externally generated flow field, allowing spatial modulation of streamlines in real time. Furthermore, we provide a characterization of the system in terms of time response and dielectric breakdown, as well as engineering guidelines for its robust design and operation. We believe that the ability to create tailored microscale flow using solid-state actuation will open the door to entirely new on-chip functionalities.},
 bibtype = {article},
 author = {Paratore, Federico and Bacheva, Vesna and Kaigala, Govind V and Bercovici, Moran},
 doi = {10.1073/pnas.1821269116},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 number = {21}
}

The ability to move fluids at the microscale is at the core of many scientific and technological advancements. Despite its importance, microscale flow control remains highly limited by the use of discrete channels and mechanical valves, and relies on fixed geometries. Here we present an alternative mechanism that leverages localized field-effect electroosmosis to create dynamic flow patterns, allowing fluid manipulation without the use of physical walls. We control a set of gate electrodes embedded in the floor of a fluidic chamber using an ac voltage in sync with an external electric field, creating nonuniform electroosmotic flow distributions. These give rise to a pressure field that drives the flow throughout the chamber. We demonstrate a range of unique flow patterns that can be achieved, including regions of recirculating flow surrounded by quiescent fluid and volumes of complete stagnation within a moving fluid. We also demonstrate the interaction of multiple gate electrodes with an externally generated flow field, allowing spatial modulation of streamlines in real time. Furthermore, we provide a characterization of the system in terms of time response and dielectric breakdown, as well as engineering guidelines for its robust design and operation. We believe that the ability to create tailored microscale flow using solid-state actuation will open the door to entirely new on-chip functionalities.

@article{
 title = {Electroosmotic Flow Dipole: Experimental Observation and Flow Field Patterning},
 type = {article},
 year = {2019},
 pages = {224502},
 volume = {122},
 websites = {https://link.aps.org/doi/10.1103/PhysRevLett.122.224502},
 month = {6},
 publisher = {American Physical Society},
 day = {7},
 id = {23286252-ce4f-39d6-996b-2227b932c784},
 created = {2019-06-19T15:44:59.892Z},
 accessed = {2019-06-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-06-19T15:45:20.293Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Paratore, Federico and Boyko, Evgeniy and Kaigala, Govind V. and Bercovici, Moran},
 doi = {10.1103/PhysRevLett.122.224502},
 journal = {Physical Review Letters},
 number = {22}
}

@article{
 title = {Dipolar thermocapillary motor and swimmer},
 type = {article},
 year = {2019},
 pages = {74002},
 volume = {4},
 publisher = {American Physical Society},
 id = {cf644a2c-a4cc-33c1-a016-fbd3f17bd950},
 created = {2020-02-13T21:38:09.140Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-02-13T21:39:25.596Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 source_type = {article},
 private_publication = {false},
 bibtype = {article},
 author = {Frumkin, Valeri and Gommed, Khaled and Bercovici, Moran},
 journal = {Physical Review Fluids},
 number = {7}
}

@article{
 title = {Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification},
 type = {article},
 year = {2019},
 pages = {15259-15262},
 volume = {58},
 id = {2c559399-008f-34c9-9d05-490421d3a93f},
 created = {2020-02-13T21:38:09.400Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-02-13T21:39:25.581Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 source_type = {article},
 private_publication = {false},
 bibtype = {article},
 author = {van Kooten, Xander F and Petrini, Lorenzo F T and Kashyap, Aditya and von Voithenberg, Lena and Bercovici, Moran and Kaigala, Govind V},
 journal = {Angewandte Chemie International Edition},
 number = {43}
}

@article{
 title = {Electrokinetic Scanning Probe},
 type = {article},
 year = {2019},
 publisher = {Wiley Online Library},
 id = {a31656d9-b1d2-307c-81cc-2a244d9582fa},
 created = {2020-02-13T21:41:51.534Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2020-02-13T21:42:01.250Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 source_type = {article},
 private_publication = {false},
 bibtype = {article},
 author = {Ostromohov, Nadya and Rofman, Baruch and Bercovici, Moran and Kaigala, Govind},
 journal = {Small}
}

@article{
 title = {Real-Time Monitoring of Fluorescence in Situ Hybridization Kinetics},
 type = {article},
 year = {2018},
 pages = {11470-11477},
 volume = {90},
 websites = {https://pubs.acs.org/doi/10.1021/acs.analchem.8b02630%0A},
 publisher = {ACS Publications},
 id = {1cbf6fc2-c0e4-3f32-8a25-edc508762223},
 created = {2019-01-20T06:08:16.839Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:13.174Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {ostromohov2018real},
 source_type = {article},
 private_publication = {false},
 abstract = {We present a novel method for real-time monitoring and kinetic analysis of fluorescence in situ hybridization (FISH). We implement the method using a vertical microfluidic probe containing a microstructure designed for rapid switching between probe solution and nonfluorescent imaging buffer. The FISH signal is monitored in real time during the imaging buffer wash, during which signal associated with unbound probes is removed. We provide a theoretical description of the method as well as a demonstration of its applicability using a model system of centromeric probes (Cen17). We demonstrate the applicability of the method for characterization of FISH kinetics under conditions of varying probe concentration, destabilizing agent (formamide) content, volume exclusion agent (dextran sulfate) content, and ionic strength. We show that our method can be used to investigate the effect of each of these variables and provide insight into processes affecting in situ hybridization, facilitating the design of new assays.},
 bibtype = {article},
 author = {Ostromohov, Nadya and Huber, Deborah and Bercovici, Moran and Kaigala, Govind V.},
 doi = {10.1021/acs.analchem.8b02630},
 journal = {Analytical Chemistry},
 number = {19}
}

We present a novel method for real-time monitoring and kinetic analysis of fluorescence in situ hybridization (FISH). We implement the method using a vertical microfluidic probe containing a microstructure designed for rapid switching between probe solution and nonfluorescent imaging buffer. The FISH signal is monitored in real time during the imaging buffer wash, during which signal associated with unbound probes is removed. We provide a theoretical description of the method as well as a demonstration of its applicability using a model system of centromeric probes (Cen17). We demonstrate the applicability of the method for characterization of FISH kinetics under conditions of varying probe concentration, destabilizing agent (formamide) content, volume exclusion agent (dextran sulfate) content, and ionic strength. We show that our method can be used to investigate the effect of each of these variables and provide insight into processes affecting in situ hybridization, facilitating the design of new assays.

@article{
 title = {Extraction of electrokinetically separated analytes with on-demand encapsulation},
 type = {article},
 year = {2018},
 pages = {3588-3597},
 volume = {18},
 websites = {https://pubs.rsc.org/en/content/articlelanding/2018/lc/c8lc00912k#!divAbstract%0A},
 publisher = {Royal Society of Chemistry},
 id = {3d47e689-ce97-3152-9eac-3f53df4c38c6},
 created = {2019-01-20T06:08:17.028Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:13.054Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {van2018extraction},
 source_type = {article},
 private_publication = {false},
 abstract = {Microchip electrokinetic methods are capable of increasing the sensitivity of molecular assays by enriching and purifying target analytes. However, their use is currently limited to assays that can be performed under a high external electric field, as spatial separation and focusing is lost when the electric field is removed. We present a novel method that uses two-phase encapsulation to overcome this limitation. The method uses passive filling and pinning of an oil phase in hydrophobic channels to encapsulate electrokinetically separated and focused analytes with a brief pressure pulse. The resulting encapsulated sample droplet maintains its concentration over long periods of time without requiring an electric field and can be manipulated for further analysis, either on- or off-chip. We demonstrate the method by encapsulating DNA oligonucleotides in a 240 pL aqueous segment after isotachophoresis (ITP) focusing, and show that the concentration remains at 60% of the initial value for tens of minutes, a 22-fold increase over free diffusion after 20 minutes. Furthermore, we demonstrate manipulation of a single droplet by selectively encapsulating amplicon after ITP purification from a polymerase chain reaction (PCR) mix, and performing parallel off-chip detection reactions using the droplet. We provide geometrical design guidelines for devices implementing the encapsulation method, and show how the method can be scaled to multiple analyte zones.},
 bibtype = {article},
 author = {van Kooten, Xander F. and Bercovici, Moran and Kaigala, Govind V.},
 doi = {10.1039/c8lc00912k},
 journal = {Lab on a chip},
 number = {23}
}

Microchip electrokinetic methods are capable of increasing the sensitivity of molecular assays by enriching and purifying target analytes. However, their use is currently limited to assays that can be performed under a high external electric field, as spatial separation and focusing is lost when the electric field is removed. We present a novel method that uses two-phase encapsulation to overcome this limitation. The method uses passive filling and pinning of an oil phase in hydrophobic channels to encapsulate electrokinetically separated and focused analytes with a brief pressure pulse. The resulting encapsulated sample droplet maintains its concentration over long periods of time without requiring an electric field and can be manipulated for further analysis, either on- or off-chip. We demonstrate the method by encapsulating DNA oligonucleotides in a 240 pL aqueous segment after isotachophoresis (ITP) focusing, and show that the concentration remains at 60% of the initial value for tens of minutes, a 22-fold increase over free diffusion after 20 minutes. Furthermore, we demonstrate manipulation of a single droplet by selectively encapsulating amplicon after ITP purification from a polymerase chain reaction (PCR) mix, and performing parallel off-chip detection reactions using the droplet. We provide geometrical design guidelines for devices implementing the encapsulation method, and show how the method can be scaled to multiple analyte zones.

@article{
 title = {Nanoliter Cell Culture Array with Tunable Chemical Gradients},
 type = {article},
 year = {2018},
 pages = {7480-7488},
 volume = {90},
 websites = {https://pubs.acs.org/doi/10.1021/acs.analchem.8b01017%0A},
 publisher = {ACS Publications},
 id = {da754154-01eb-3601-952b-14bc112e2183},
 created = {2019-01-20T06:08:17.344Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:13.019Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {avesar2018nanoliter},
 source_type = {article},
 private_publication = {false},
 abstract = {A multitude of cell screening assays for diagnostic and research applications rely on quantitative measurements of a sample in the presence of different reagent concentrations. Standard methods rely on microtiter plates of varying well density, which provide simple and standardized sample addressability. However, testing hundreds of chemical dilutions requires complex automation, and typical well volumes of microtiter plates are incompatible with the analysis of a small number of cells. Here, we present a microfluidic device for creating a high-resolution chemical gradient spanning 200 nanoliter wells. Using air-based shearing, we show that the individual wells can be compartmentalized without altering the concentration gradient, resulting in a large set of isolated nanoliter cell culture wells. We provide an analytical and numerical model for predicting the concentration within each culture chamber and validate it against experimental results. We apply our system for the investigation of yeast cell metabolic gene regulation in the presence of different ratios of galactose/glucose concentrations and successfully resolve the nutrient threshold at which the cells activate the galactose pathway. A large number of cell analysis studies rely on testing the response of cells to a range of reagent concentrations. The microtiter plate has been the most widely used format for performing such studies, providing a standard format for addressing up to hundreds or thousands of individual test chambers, with volumes as low as a few microliters. Such compartmentalization is key in ensuring that the contents of each well remain isolated from its neighbors, yielding a large set of independent experiments. In addition, microtiter plates support the culture of both cells in suspension and of adherent cells attached to a tissue culture surface. Despite these advantages, microtiter well volumes are still relatively large for single cell analysis applications where volumes must be small enough to yield a detectable concentration of the analyte of interest. In addition, testing hundreds of reagent concentrations using microtiter plates can be laborious or require the use of complex and expensive robotics. This together with often limited volume of precious samples led to the development of microfluidic based solutions. 1−3},
 bibtype = {article},
 author = {Avesar, Jonathan and Blinder, Yaron and Aktin, Hadar and Szklanny, Ariel and Rosenfeld, Dekel and Savir, Yonatan and Bercovici, Moran and Levenberg, Shulamit},
 doi = {10.1021/acs.analchem.8b01017},
 journal = {Analytical Chemistry},
 number = {12}
}

A multitude of cell screening assays for diagnostic and research applications rely on quantitative measurements of a sample in the presence of different reagent concentrations. Standard methods rely on microtiter plates of varying well density, which provide simple and standardized sample addressability. However, testing hundreds of chemical dilutions requires complex automation, and typical well volumes of microtiter plates are incompatible with the analysis of a small number of cells. Here, we present a microfluidic device for creating a high-resolution chemical gradient spanning 200 nanoliter wells. Using air-based shearing, we show that the individual wells can be compartmentalized without altering the concentration gradient, resulting in a large set of isolated nanoliter cell culture wells. We provide an analytical and numerical model for predicting the concentration within each culture chamber and validate it against experimental results. We apply our system for the investigation of yeast cell metabolic gene regulation in the presence of different ratios of galactose/glucose concentrations and successfully resolve the nutrient threshold at which the cells activate the galactose pathway. A large number of cell analysis studies rely on testing the response of cells to a range of reagent concentrations. The microtiter plate has been the most widely used format for performing such studies, providing a standard format for addressing up to hundreds or thousands of individual test chambers, with volumes as low as a few microliters. Such compartmentalization is key in ensuring that the contents of each well remain isolated from its neighbors, yielding a large set of independent experiments. In addition, microtiter plates support the culture of both cells in suspension and of adherent cells attached to a tissue culture surface. Despite these advantages, microtiter well volumes are still relatively large for single cell analysis applications where volumes must be small enough to yield a detectable concentration of the analyte of interest. In addition, testing hundreds of reagent concentrations using microtiter plates can be laborious or require the use of complex and expensive robotics. This together with often limited volume of precious samples led to the development of microfluidic based solutions. 1−3

@article{
 title = {Amplification-free detection of DNA in a paper-based microfluidic device using electroosmotically balanced isotachophoresis},
 type = {article},
 year = {2018},
 pages = {861-868},
 volume = {18},
 websites = {https://pubs.rsc.org/en/content/articlelanding/2018/lc/c7lc01250k#!divAbstract%0A},
 publisher = {Royal Society of Chemistry},
 id = {862e445e-d899-3652-9390-2641cfae883d},
 created = {2019-01-20T06:08:17.733Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.895Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {rosenfeld2018amplification},
 source_type = {article},
 private_publication = {false},
 abstract = {We present a novel microfluidic paper-based analytical device (μPAD) which utilizes the native high electroosmotic flow (EOF) in nitrocellulose to achieve stationary isotachophoresis (ITP) focusing. This approach decouples sample accumulation from the length of the channel, resulting in significant focusing over short channel lengths. We provide a brief theory for EOF-balanced ITP focusing under continuous injection from a depleting reservoir and present the design of a short (7 mm) paper-based microfluidic channel, which allows a 200 μL sample to be processed in approximately 6 min, resulting in a 20 000-fold increase in concentration – a full order of magnitude improvement compared to previous paper-based ITP devices. We show the stability of the assay over longer (40 min) durations of time, and using Morpholino probes, we present the applicability of the device for amplification-free detection of nucleic acids, with a limit-of-detection (LoD) of 5 pM in 10 min. Finally, we utilize the small footprint of the channel and show a multiplexed platform in which 12 assays operate in parallel in a 24-well plate format.},
 bibtype = {article},
 author = {Rosenfeld, Tally and Bercovici, Moran},
 doi = {10.1039/c7lc01250k},
 journal = {Lab on a Chip},
 number = {6}
}

We present a novel microfluidic paper-based analytical device (μPAD) which utilizes the native high electroosmotic flow (EOF) in nitrocellulose to achieve stationary isotachophoresis (ITP) focusing. This approach decouples sample accumulation from the length of the channel, resulting in significant focusing over short channel lengths. We provide a brief theory for EOF-balanced ITP focusing under continuous injection from a depleting reservoir and present the design of a short (7 mm) paper-based microfluidic channel, which allows a 200 μL sample to be processed in approximately 6 min, resulting in a 20 000-fold increase in concentration – a full order of magnitude improvement compared to previous paper-based ITP devices. We show the stability of the assay over longer (40 min) durations of time, and using Morpholino probes, we present the applicability of the device for amplification-free detection of nucleic acids, with a limit-of-detection (LoD) of 5 pM in 10 min. Finally, we utilize the small footprint of the channel and show a multiplexed platform in which 12 assays operate in parallel in a 24-well plate format.

@article{
 title = {Monitoring Dissociation Kinetics during Electrophoretic Focusing to Enable High‐Specificity Nucleic Acid Detection},
 type = {article},
 year = {2018},
 keywords = {isotachophoresis,morpholino probes,nucleic acids,reaction kinetics,specificity},
 pages = {3343-3348},
 volume = {57},
 websites = {https://doi.org/10.1002/anie.201711673},
 id = {2b815f7b-5249-34fb-a6e5-b872e8add2de},
 created = {2019-01-20T06:08:18.029Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.877Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {zeidman2018monitoring},
 source_type = {article},
 private_publication = {false},
 abstract = {Abstract A wide range of medical conditions can be diagnosed through sequence?specific analysis of nucleic acids. However, a major challenge remains in detecting a specific target in samples containing a high concentration of mismatching sequences. A single?step kinetic homogenous (free solution) assay is presented in which free sequence?specific probes are continuously separated from probe?target hybrids during electrophoretic sample focusing, allowing monitoring of dissociation kinetics. Under these conditions, the different kinetics of targets versus mismatches result in distinct patterns of the signal (for example, linear increase for target versus exponential decay for mismatch), allowing the detection of desired sequences even in the presence of high background nucleic acid content. Additionally, an analytical model provides insight into the underlying dynamics, and allows design of assays based on this mechanism.},
 bibtype = {article},
 author = {Tal, Zeidman Kalman and Rebecca, Khalandovsky and Elena, Tenenbaum Gonikman and Moran, Bercovici},
 doi = {doi:10.1002/anie.201711673},
 journal = {Angewandte Chemie International Edition},
 number = {13}
}

Abstract A wide range of medical conditions can be diagnosed through sequence?specific analysis of nucleic acids. However, a major challenge remains in detecting a specific target in samples containing a high concentration of mismatching sequences. A single?step kinetic homogenous (free solution) assay is presented in which free sequence?specific probes are continuously separated from probe?target hybrids during electrophoretic sample focusing, allowing monitoring of dissociation kinetics. Under these conditions, the different kinetics of targets versus mismatches result in distinct patterns of the signal (for example, linear increase for target versus exponential decay for mismatch), allowing the detection of desired sequences even in the presence of high background nucleic acid content. Additionally, an analytical model provides insight into the underlying dynamics, and allows design of assays based on this mechanism.

@article{
 title = {Isotachophoresis-Based Surface Immunoassay},
 type = {article},
 year = {2017},
 pages = {7373-7381},
 volume = {89},
 websites = {http://pubs.acs.org/doi/10.1021/acs.analchem.7b00725},
 month = {7},
 day = {18},
 id = {951dbe55-217a-37ab-b2d5-ba9350a434b0},
 created = {2019-01-20T05:44:38.492Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.595Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {In the absence of amplification methods for proteins, the immune-detection of low-abundance proteins using antibodies is fundamentally limited by binding kinetic rates. Here, we present a new class of surface-based immunoassays in which protein–antibody reaction is accelerated by isotachophoresis (ITP). We demonstrate the use of ITP to preconcentrate and deliver target proteins to a surface decorated with specific antibodies, where effective utilization of the focused sample is achieved by modulating the driving electric field (stop-and-diffuse ITP mode) or applying a counter flow that opposes the ITP motion (counterflow ITP mode). Using enhanced green fluorescent protein (EGFP) as a model protein, we carry out an experimental optimization of the ITP-based immunoassay and demonstrate a 1300-fold improvement in limit of detection compared to a standard immunoassay, in a 6 min protein–antibody reaction. We discuss the design of buffer chemistries for other protein systems and, in concert with experiments, p...},
 bibtype = {article},
 author = {Paratore, Federico and Zeidman Kalman, Tal and Rosenfeld, Tally and Kaigala, Govind V. and Bercovici, Moran},
 doi = {10.1021/acs.analchem.7b00725},
 journal = {Analytical Chemistry},
 number = {14}
}

In the absence of amplification methods for proteins, the immune-detection of low-abundance proteins using antibodies is fundamentally limited by binding kinetic rates. Here, we present a new class of surface-based immunoassays in which protein–antibody reaction is accelerated by isotachophoresis (ITP). We demonstrate the use of ITP to preconcentrate and deliver target proteins to a surface decorated with specific antibodies, where effective utilization of the focused sample is achieved by modulating the driving electric field (stop-and-diffuse ITP mode) or applying a counter flow that opposes the ITP motion (counterflow ITP mode). Using enhanced green fluorescent protein (EGFP) as a model protein, we carry out an experimental optimization of the ITP-based immunoassay and demonstrate a 1300-fold improvement in limit of detection compared to a standard immunoassay, in a 6 min protein–antibody reaction. We discuss the design of buffer chemistries for other protein systems and, in concert with experiments, p...

@article{
 title = {Rapid phenotypic antimicrobial susceptibility testing using nanoliter arrays},
 type = {article},
 year = {2017},
 pages = {E5787-E5795},
 volume = {114},
 websites = {http://www.pnas.org/lookup/doi/10.1073/pnas.1703736114},
 id = {493e2fb2-8a11-386b-8710-354520cf7cf7},
 created = {2019-01-20T05:44:38.517Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:19.062Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Antibiotic resistance is a major global health concern that requires action across all sectors of society. In particular, to allow conservative and effective use of antibiotics clinical settings require better diagnostic tools that provide rapid determination of antimicrobial susceptibility. We present a method for rapid and scalable antimicrobial susceptibility testing using stationary nanoliter droplet arrays that is capable of delivering results in approximately half the time of conventional methods, allowing its results to be used the same working day. In addition, we present an algorithm for automated data analysis and a multiplexing system promoting practicality and translatability for clinical settings. We test the efficacy of our approach on numerous clinical isolates and demonstrate a 2-d reduction in diagnostic time when testing bacteria isolated directly from urine samples.},
 bibtype = {article},
 author = {Avesar, Jonathan and Rosenfeld, Dekel and Truman-Rosentsvit, Marianna and Ben-Arye, Tom and Geffen, Yuval and Bercovici, Moran and Levenberg, Shulamit},
 doi = {10.1073/pnas.1703736114},
 journal = {Proceedings of the National Academy of Sciences},
 number = {29}
}

Antibiotic resistance is a major global health concern that requires action across all sectors of society. In particular, to allow conservative and effective use of antibiotics clinical settings require better diagnostic tools that provide rapid determination of antimicrobial susceptibility. We present a method for rapid and scalable antimicrobial susceptibility testing using stationary nanoliter droplet arrays that is capable of delivering results in approximately half the time of conventional methods, allowing its results to be used the same working day. In addition, we present an algorithm for automated data analysis and a multiplexing system promoting practicality and translatability for clinical settings. We test the efficacy of our approach on numerous clinical isolates and demonstrate a 2-d reduction in diagnostic time when testing bacteria isolated directly from urine samples.

@article{
 title = {Elastic deformations driven by non-uniform lubrication flows},
 type = {article},
 year = {2017},
 keywords = {Fluid-structure interactions,Hele-Shaw flows,Microfluidics},
 pages = {841-865},
 volume = {812},
 websites = {https://www.cambridge.org/core/journals/journal-of-fluid-mechanics/article/elastic-deformations-driven-by-nonuniform-lubrication-flows/F5F731A69950B9AAE1D6806184BA88E8},
 id = {143faeda-77f6-386d-8f79-9562fe51b9a3},
 created = {2019-01-20T05:45:06.270Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.082Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {The ability to create dynamic deformations of micron-sized structures is relevant to a wide variety of applications such as adaptable optics, soft robotics and reconfigurable microfluidic devices. In this work, we examine non-uniform lubrication flow as a mechanism to create complex deformation fields in an elastic plate. We consider a Kirchhoff–Love elasticity model for the plate and Hele-Shaw flow in a narrow gap between the plate and a parallel rigid surface. Based on linearization of the Reynolds equation, we obtain a governing equation which relates elastic deformations to gradients in non-homogeneous physical properties of the fluid (e.g. body forces, viscosity and slip velocity). We then focus on a specific case of non-uniform Helmholtz–Smoluchowski electro-osmotic slip velocity, and provide a method for determining the zeta-potential distribution necessary to generate arbitrary static and quasi-static deformations of the elastic plate. Extending the problem to time-dependent solutions, we analyse transient effects on asymptotically static solutions, and finally provide a closed form solution for a Green's function for time periodic actuations.},
 bibtype = {article},
 author = {Rubin, Shimon and Tulchinsky, Arie and Gat, Amir D. and Bercovici, Moran},
 doi = {10.1017/jfm.2016.830},
 journal = {Journal of Fluid Mechanics}
}

The ability to create dynamic deformations of micron-sized structures is relevant to a wide variety of applications such as adaptable optics, soft robotics and reconfigurable microfluidic devices. In this work, we examine non-uniform lubrication flow as a mechanism to create complex deformation fields in an elastic plate. We consider a Kirchhoff–Love elasticity model for the plate and Hele-Shaw flow in a narrow gap between the plate and a parallel rigid surface. Based on linearization of the Reynolds equation, we obtain a governing equation which relates elastic deformations to gradients in non-homogeneous physical properties of the fluid (e.g. body forces, viscosity and slip velocity). We then focus on a specific case of non-uniform Helmholtz–Smoluchowski electro-osmotic slip velocity, and provide a method for determining the zeta-potential distribution necessary to generate arbitrary static and quasi-static deformations of the elastic plate. Extending the problem to time-dependent solutions, we analyse transient effects on asymptotically static solutions, and finally provide a closed form solution for a Green's function for time periodic actuations.

@article{
 title = {On Chip Protein Pre-Concentration for Enhancing the Sensitivity of Porous Silicon Biosensors},
 type = {article},
 year = {2017},
 keywords = {aptamer,isotachophoresis,label-free,optical biosensor,porous silicon},
 pages = {1767-1773},
 volume = {2},
 websites = {https://pubs.acs.org/doi/abs/10.1021/acssensors.7b00692},
 id = {334d042a-7e81-3bae-b39c-02e1194e25f8},
 created = {2019-01-20T05:45:06.450Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.632Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {The liver is covered by visceral peritoneum except at the bare area, bed of the gallbladder, and porta hepatis. The investing peritoneum becomes contiguous with the adjacent structures such as the diaphragmatic peritoneum, lesser omentum, and ligamentum teres. An inflammatory process or tumors involving the perihepatic space are usually affected by intraperitoneal flow dynamics, which depend on the anatomy of the recess as well as gravity and negative subdiaphragmatic pressure. Pathologic conditions that occur in the perihepatic space include abnormal air, fatty masses, conditions producing fluid attenuation at computed tomography (CT), and soft-tissue masses. Enhancement of the hepatic capsule indicates inflammation, as is seen in Fitz-Hugh-Curtis syndrome. The perihepatic ligaments may be invaded by various conditions by means of direct invasion, subperitoneal extension, or extension along the lymphatic vessels. Knowledge of the normal anatomy of the perihepatic space together with the clinical history and characteristic features at CT can assist the radiologist in making the correct diagnosis. Copyright RSNA, 2007.},
 bibtype = {article},
 author = {Arshavsky-Graham, Sofia and Massad-Ivanir, Naama and Paratore, Federico and Scheper, Thomas and Bercovici, Moran and Segal, Ester},
 doi = {10.1021/acssensors.7b00692},
 journal = {ACS Sensors},
 number = {12}
}

The liver is covered by visceral peritoneum except at the bare area, bed of the gallbladder, and porta hepatis. The investing peritoneum becomes contiguous with the adjacent structures such as the diaphragmatic peritoneum, lesser omentum, and ligamentum teres. An inflammatory process or tumors involving the perihepatic space are usually affected by intraperitoneal flow dynamics, which depend on the anatomy of the recess as well as gravity and negative subdiaphragmatic pressure. Pathologic conditions that occur in the perihepatic space include abnormal air, fatty masses, conditions producing fluid attenuation at computed tomography (CT), and soft-tissue masses. Enhancement of the hepatic capsule indicates inflammation, as is seen in Fitz-Hugh-Curtis syndrome. The perihepatic ligaments may be invaded by various conditions by means of direct invasion, subperitoneal extension, or extension along the lymphatic vessels. Knowledge of the normal anatomy of the perihepatic space together with the clinical history and characteristic features at CT can assist the radiologist in making the correct diagnosis. Copyright RSNA, 2007.

@article{
 title = {Viscous-elastic dynamics of power-law fluids within an elastic cylinder},
 type = {article},
 year = {2017},
 pages = {073301},
 volume = {2},
 websites = {https://journals.aps.org/prfluids/abstract/10.1103/PhysRevFluids.2.073301%0A},
 publisher = {American Physical Society},
 id = {d233f4a0-2447-3d9b-a006-d66fd280d2e9},
 created = {2019-01-20T06:08:17.882Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:13.289Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {boyko2017viscous},
 source_type = {article},
 private_publication = {false},
 abstract = {In a wide range of applications, microfluidic channels are implemented in soft substrates. In such configurations, where fluidic inertia and compressibility are negligible, the propagation of fluids in channels is governed by a balance between fluid viscosity and elasticity of the surrounding solid. The viscous-elastic interactions between elastic substrates and non-Newtonian fluids are particularly of interest due to the dependence of viscosity on the state of the system. In this work, we study the fluid-structure interaction dynamics between an incompressible non-Newtonian fluid and a slender linearly elastic cylinder under the creeping flow regime. Considering power-law fluids and applying the thin shell approximation for the elastic cylinder, we obtain a nonhomogeneous p-Laplacian equation governing the viscous-elastic dynamics. We present exact solutions for the pressure and deformation fields for various initial and boundary conditions for both shear-thinning and shear-thickening fluids. We show that in contrast to Stokes’ problem where a compactly supported front is obtained for shear-thickening fluids, here the role of viscosity is inversed and such fronts are obtained for shear-thinning fluids. Furthermore, we demonstrate that n for the case of a step in inlet pressure, the propagation rate of the front has a t n+1 dependence on time (t), suggesting the ability to indirectly measure the power-law index (n) of shear-thinning liquids through measurements of elastic deformation.},
 bibtype = {article},
 author = {Boyko, E. and Bercovici, M. and Gat, A. D.},
 doi = {10.1103/PhysRevFluids.2.073301},
 journal = {Phys. Rev. Fluids},
 number = {7}
}

In a wide range of applications, microfluidic channels are implemented in soft substrates. In such configurations, where fluidic inertia and compressibility are negligible, the propagation of fluids in channels is governed by a balance between fluid viscosity and elasticity of the surrounding solid. The viscous-elastic interactions between elastic substrates and non-Newtonian fluids are particularly of interest due to the dependence of viscosity on the state of the system. In this work, we study the fluid-structure interaction dynamics between an incompressible non-Newtonian fluid and a slender linearly elastic cylinder under the creeping flow regime. Considering power-law fluids and applying the thin shell approximation for the elastic cylinder, we obtain a nonhomogeneous p-Laplacian equation governing the viscous-elastic dynamics. We present exact solutions for the pressure and deformation fields for various initial and boundary conditions for both shear-thinning and shear-thickening fluids. We show that in contrast to Stokes’ problem where a compactly supported front is obtained for shear-thickening fluids, here the role of viscosity is inversed and such fronts are obtained for shear-thinning fluids. Furthermore, we demonstrate that n for the case of a step in inlet pressure, the propagation rate of the front has a t n+1 dependence on time (t), suggesting the ability to indirectly measure the power-law index (n) of shear-thinning liquids through measurements of elastic deformation.

@article{
 title = {Focusing analytes from 50 μl into 500 pL: On-chip focusing from large sample volumes using isotachophoresis},
 type = {article},
 year = {2017},
 volume = {7},
 id = {5a172ae5-6cd7-3610-9e69-295d92e5e377},
 created = {2019-05-22T05:20:22.673Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-05-22T05:20:22.673Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {true},
 abstract = {© 2017 The Author(s). The use of on-chip isotachophoresis assays for diagnostic applications is often limited by the small volumes of standard microfluidic channels. Overcoming this limitation is particularly important for detection of 'discrete' biological targets (such as bacteria) at low concentrations, where the volume of processed liquid in a standard microchannel might not contain any targets. We present a novel microfluidic chip that enables ITP focusing of target analytes from initial sample volumes of 50 μL into a concentrated zone with a volume of 500 pL, corresponding to a 100,000-fold increase in mean concentration, and a 300,000-fold increase in peak concentration. We present design considerations for limiting sample dispersion in such large-volume focusing (LVF) chips and discuss the trade-off between assay time and Joule heating, which ultimately governs the scalability of LVF designs. Finally, we demonstrate a 100-fold improvement of ITP focusing performance in the LVF chip as compared to conventional microchannels, and apply this enhancement to achieve highly sensitive detection of both molecular targets (DNA, down to 10 fM) and whole bacteria (down to 100 cfu/mL).},
 bibtype = {article},
 author = {Van Kooten, X.F. and Truman-Rosentsvit, M. and Kaigala, G.V. and Bercovici, M.},
 doi = {10.1038/s41598-017-10579-5},
 journal = {Scientific Reports},
 number = {1}
}

© 2017 The Author(s). The use of on-chip isotachophoresis assays for diagnostic applications is often limited by the small volumes of standard microfluidic channels. Overcoming this limitation is particularly important for detection of 'discrete' biological targets (such as bacteria) at low concentrations, where the volume of processed liquid in a standard microchannel might not contain any targets. We present a novel microfluidic chip that enables ITP focusing of target analytes from initial sample volumes of 50 μL into a concentrated zone with a volume of 500 pL, corresponding to a 100,000-fold increase in mean concentration, and a 300,000-fold increase in peak concentration. We present design considerations for limiting sample dispersion in such large-volume focusing (LVF) chips and discuss the trade-off between assay time and Joule heating, which ultimately governs the scalability of LVF designs. Finally, we demonstrate a 100-fold improvement of ITP focusing performance in the LVF chip as compared to conventional microchannels, and apply this enhancement to achieve highly sensitive detection of both molecular targets (DNA, down to 10 fM) and whole bacteria (down to 100 cfu/mL).

@article{
 title = {Flow of power-law liquids in a Hele-Shaw cell driven by non-uniform electro-osmotic slip in the case of strong depletion},
 type = {article},
 year = {2016},
 keywords = {Hele-Shaw flows,microfluidics,non-Newtonian flows},
 pages = {235-257},
 volume = {807},
 websites = {https://www.cambridge.org/core/journals/journal-of-fluid-mechanics/article/flow-of-powerlaw-liquids-in-a-heleshaw-cell-driven-by-nonuniform-electroosmotic-slip-in-the-case-of-strong-depletion/54227A5E7DE796452B7F822880452928},
 id = {d1240755-9f68-3a3d-a805-5080d455430a},
 created = {2019-01-20T05:45:06.496Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:13.216Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We analyse flow of non-Newtonian fluids in a Hele-Shaw cell, subjected to spatially non-uniform electro-osmotic slip. Motivated by their potential use for increasing the characteristic pressure fields, we specifically focus on power-law fluids with wall depletion properties. We derive a $p$ -Poisson equation governing the pressure field, as well as a set of linearized equations representing its asymptotic approximation for weakly non-Newtonian behaviour. To investigate the effect of non-Newtonian properties on the resulting fluidic pressure and velocity, we consider several configurations in one and two dimensions, and calculate both exact and approximate solutions. We show that the asymptotic approximation is in good agreement with exact solutions even for fluids with significant non-Newtonian behaviour, allowing its use in the analysis and design of microfluidic systems involving electrokinetic transport of such fluids.},
 bibtype = {article},
 author = {Boyko, Evgeniy and Bercovici, Moran and Gat, Amir D.},
 doi = {10.1017/jfm.2016.622},
 journal = {Journal of Fluid Mechanics}
}

We analyse flow of non-Newtonian fluids in a Hele-Shaw cell, subjected to spatially non-uniform electro-osmotic slip. Motivated by their potential use for increasing the characteristic pressure fields, we specifically focus on power-law fluids with wall depletion properties. We derive a $p$ -Poisson equation governing the pressure field, as well as a set of linearized equations representing its asymptotic approximation for weakly non-Newtonian behaviour. To investigate the effect of non-Newtonian properties on the resulting fluidic pressure and velocity, we consider several configurations in one and two dimensions, and calculate both exact and approximate solutions. We show that the asymptotic approximation is in good agreement with exact solutions even for fluids with significant non-Newtonian behaviour, allowing its use in the analysis and design of microfluidic systems involving electrokinetic transport of such fluids.

@article{
 title = {Delivery of minimally dispersed liquid interfaces for sequential surface chemistry},
 type = {article},
 year = {2016},
 pages = {3015-3023},
 volume = {16},
 websites = {https://pubs.rsc.org/en/content/articlelanding/2016/lc/c6lc00473c#!divAbstract%0A},
 publisher = {Royal Society of Chemistry},
 id = {4b03b9fe-dc9a-3425-9f83-8b139d3b77a4},
 created = {2019-01-20T06:08:16.520Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.681Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {ostromohov2016delivery},
 source_type = {article},
 private_publication = {false},
 abstract = {We present a method for sequential delivery of reagents to a reaction site with minimal dispersion of their interfaces. Using segmented flow to encapsulate the reagents as droplets, the dispersion between reagent plugs remains confined in a limited volume, while being transmitted to the reaction surface. In close prox-imity to the target surface, we use a passive array of microstructures for removal of the oil phase such that the original reagent sequence is reconstructed, and only the aqueous phase reaches the reaction surface. We provide a detailed analysis of the conditions under which the method can be applied and demonstrate maintaining a transition time of 560 ms between reagents transported to a reaction site over a distance of 60 cm. We implemented the method using a vertical microfluidic probe on an open surface, allowing contact-free interaction with biological samples, and demonstrated two examples of assays implemented using the method: measurements of receptor–ligand reaction kinetics and of the fluorescence response of immobilized GFP to local variations in pH. We believe that the method can be useful for studying the dy-namic response of cells and proteins to various stimuli, as well as for highly automated multi-step assays.},
 bibtype = {article},
 author = {Ostromohov, N. and Bercovici, M. and Kaigala, G. V.},
 doi = {10.1039/c6lc00473c},
 journal = {Lab on a Chip},
 number = {16}
}

We present a method for sequential delivery of reagents to a reaction site with minimal dispersion of their interfaces. Using segmented flow to encapsulate the reagents as droplets, the dispersion between reagent plugs remains confined in a limited volume, while being transmitted to the reaction surface. In close prox-imity to the target surface, we use a passive array of microstructures for removal of the oil phase such that the original reagent sequence is reconstructed, and only the aqueous phase reaches the reaction surface. We provide a detailed analysis of the conditions under which the method can be applied and demonstrate maintaining a transition time of 560 ms between reagents transported to a reaction site over a distance of 60 cm. We implemented the method using a vertical microfluidic probe on an open surface, allowing contact-free interaction with biological samples, and demonstrated two examples of assays implemented using the method: measurements of receptor–ligand reaction kinetics and of the fluorescence response of immobilized GFP to local variations in pH. We believe that the method can be useful for studying the dy-namic response of cells and proteins to various stimuli, as well as for highly automated multi-step assays.

@article{
 title = {Induced-Charge Capacitive Deionization: The Electrokinetic Response of a Porous Particle to an External Electric Field},
 type = {article},
 year = {2016},
 pages = {234502},
 volume = {117},
 websites = {https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.117.234502%0A},
 publisher = {American Physical Society},
 id = {8b4fa4af-6deb-31b5-a8cb-ef1ec3f7dc71},
 created = {2019-01-20T06:08:16.796Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.697Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {rubin2016induced},
 source_type = {article},
 private_publication = {false},
 abstract = {We demonstrate the phenomenon of induced-charge capacitive deionization (ICCDI) that occurs around a porous and conducting particle immersed in an electrolyte, under the action of an external electric field. The external electric field induces an electric dipole in the porous particle, leading to its capacitive charging by both cations and anions at opposite poles. This regime is characterized by a long charging time which results in significant changes in salt concentration in the electrically neutral bulk, on the scale of the particle. We qualitatively demonstrate the effect of advection on the spatio-temporal concentration field which, through diffusiophoresis, may introduce corrections to the electrophoretic mobility of such particles.},
 bibtype = {article},
 author = {Rubin, S. and Suss, M. E. and Biesheuvel, P. M. and Bercovici, M.},
 doi = {10.1103/PhysRevLett.117.234502},
 journal = {Physical Review Letters},
 number = {23}
}

We demonstrate the phenomenon of induced-charge capacitive deionization (ICCDI) that occurs around a porous and conducting particle immersed in an electrolyte, under the action of an external electric field. The external electric field induces an electric dipole in the porous particle, leading to its capacitive charging by both cations and anions at opposite poles. This regime is characterized by a long charging time which results in significant changes in salt concentration in the electrically neutral bulk, on the scale of the particle. We qualitatively demonstrate the effect of advection on the spatio-temporal concentration field which, through diffusiophoresis, may introduce corrections to the electrophoretic mobility of such particles.

@article{
 title = {Oxidized Porous Silicon Nanostructures Enabling Electrokinetic Transport for Enhanced DNA Detection},
 type = {article},
 year = {2015},
 keywords = {DNA,electrokinetic focusing,electrophoresis,optical biosensors,porous silicon},
 pages = {6725-6732},
 volume = {25},
 websites = {https://doi.org/10.1002/adfm.201502859},
 id = {43455a25-f4f4-38af-9d54-48bfa609617b},
 created = {2019-01-20T05:28:08.465Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.288Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Vilensky},
 private_publication = {false},
 abstract = {Nanostructured porous silicon (PSi) is a promising material for the label?free detection of biomolecules, but it currently suffers from limited applicability due to poor sensitivity, typically in micromolar range. This work presents the design, operation concept, and characterization of a novel microfluidic device and assay that integrates an oxidized PSi optical biosensor with electrokinetic focusing for a highly sensitive label?free detection of nucleic acids. Under proper oxidation conditions, the delicate nanostructure of PSi can be preserved, while providing sufficient dielectric insulation for application of high voltages. This enables the use of signal enhancement techniques, which are based on electric fields. Here, the DNA target molecules are focused using an electric field within a finite and confined zone, and this highly concentrated analyte is delivered to an on?chip PSi Fabry?Pérot optical transducer, prefunctionalized with capture probes. Using reflective interferometric Fourier transform spectroscopy real?time monitoring, a 1000?fold improvement in limit of detection is demonstrated compared to a standard assay, using the same biosensor. Thus, a measured limit of detection of 1 ? 10?9 m is achieved without compromising specificity. The concepts presented herein can be readily applied to other ionic targets, paving way for the development of other highly sensitive chemical and biochemical assays.},
 bibtype = {article},
 author = {Rita, Vilensky and Moran, Bercovici and Ester, Segal},
 doi = {10.1002/adfm.201502859},
 journal = {Advanced Functional Materials},
 number = {43}
}

Nanostructured porous silicon (PSi) is a promising material for the label?free detection of biomolecules, but it currently suffers from limited applicability due to poor sensitivity, typically in micromolar range. This work presents the design, operation concept, and characterization of a novel microfluidic device and assay that integrates an oxidized PSi optical biosensor with electrokinetic focusing for a highly sensitive label?free detection of nucleic acids. Under proper oxidation conditions, the delicate nanostructure of PSi can be preserved, while providing sufficient dielectric insulation for application of high voltages. This enables the use of signal enhancement techniques, which are based on electric fields. Here, the DNA target molecules are focused using an electric field within a finite and confined zone, and this highly concentrated analyte is delivered to an on?chip PSi Fabry?Pérot optical transducer, prefunctionalized with capture probes. Using reflective interferometric Fourier transform spectroscopy real?time monitoring, a 1000?fold improvement in limit of detection is demonstrated compared to a standard assay, using the same biosensor. Thus, a measured limit of detection of 1 ? 10?9 m is achieved without compromising specificity. The concepts presented herein can be readily applied to other ionic targets, paving way for the development of other highly sensitive chemical and biochemical assays.

@article{
 title = {Focused upon Hybridization: Rapid and High Sensitivity Detection of DNA Using Isotachophoresis and Peptide Nucleic Acid Probes},
 type = {article},
 year = {2015},
 pages = {9459-9466},
 volume = {87},
 websites = {http://pubs.acs.org/doi/10.1021/acs.analchem.5b02547},
 month = {9},
 day = {15},
 id = {8e2d7d2e-05f0-3e3f-b09d-24ba889de6f4},
 created = {2019-01-20T05:44:38.299Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.390Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present a novel assay for rapid and high sensitivity detection of nucleic acids without amplification. Utilizing the neutral backbone of peptide nucleic acids (PNA), our method is based on the design of low electrophoretic mobility PNA probes, which do not focus under isotachophoresis (ITP) unless bound to their target sequence. Thus, background noise associated with free probes is entirely eliminated, significantly improving the signal-to-noise ratio while maintaining a simple single-step assay requiring no amplification steps. We provide a detailed analytical model and experimentally demonstrate the ability to detect targets as short as 17 nucleotides (nt) and a limit of detection of 100 fM with a dynamic range of 5 decades. We also demonstrate that the assay can be successfully implemented for detection of DNA in human serum without loss of signal. The assay requires 15 min to complete, and it could potentially be used in applications where rapid and highly sensitive amplification- free detection of nucleic acids is desired},
 bibtype = {article},
 author = {Ostromohov, Nadya and Schwartz, Ortal and Bercovici, Moran},
 doi = {10.1021/acs.analchem.5b02547},
 journal = {Analytical Chemistry},
 number = {18}
}

We present a novel assay for rapid and high sensitivity detection of nucleic acids without amplification. Utilizing the neutral backbone of peptide nucleic acids (PNA), our method is based on the design of low electrophoretic mobility PNA probes, which do not focus under isotachophoresis (ITP) unless bound to their target sequence. Thus, background noise associated with free probes is entirely eliminated, significantly improving the signal-to-noise ratio while maintaining a simple single-step assay requiring no amplification steps. We provide a detailed analytical model and experimentally demonstrate the ability to detect targets as short as 17 nucleotides (nt) and a limit of detection of 100 fM with a dynamic range of 5 decades. We also demonstrate that the assay can be successfully implemented for detection of DNA in human serum without loss of signal. The assay requires 15 min to complete, and it could potentially be used in applications where rapid and highly sensitive amplification- free detection of nucleic acids is desired

@article{
 title = {Flow patterning in Hele-Shaw configurations using non-uniform electro-osmotic slip},
 type = {article},
 year = {2015},
 volume = {27},
 websites = {https://aip.scitation.org/doi/abs/10.1063/1.4931637},
 id = {b0d499f3-1d06-3f85-b0ba-3f16184b775a},
 created = {2019-01-20T05:44:38.680Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.699Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present an analytical study of electro-osmotic flow in a Hele-Shaw configuration with non-uniform zeta potential distribution. Applying the lubrication approximation and assuming thin electric double layer, we obtain a pair of uncoupled Poisson equations for the pressure and depth-averaged stream function, and show that the inhomogeneous parts in these equations are governed by gradients in zeta potential parallel and perpendicular to the applied electric field, respectively. We obtain a solution for the case of a disk-shaped region with uniform zeta potential and show that the flow field created is an exact dipole, even in the immediate vicinity of the disk. In addition, we study the inverse problem where the desired flow field is known and solve for the zeta potential distribution required in order to establish it. Finally, we demonstrate that such inverse problem solutions can be used to create directional flows confined within narrow regions, without physical walls. Such solutions are equivalent to flow within channels and we show that these can be assembled to create complex microfluidic networks, composed of intersecting channels and turns, which are basic building blocks in microfluidic devices.},
 bibtype = {article},
 author = {Boyko, Evgeniy and Rubin, Shimon and Gat, Amir D. and Bercovici, Moran},
 doi = {10.1063/1.4931637},
 journal = {Physics of Fluids},
 number = {10}
}

We present an analytical study of electro-osmotic flow in a Hele-Shaw configuration with non-uniform zeta potential distribution. Applying the lubrication approximation and assuming thin electric double layer, we obtain a pair of uncoupled Poisson equations for the pressure and depth-averaged stream function, and show that the inhomogeneous parts in these equations are governed by gradients in zeta potential parallel and perpendicular to the applied electric field, respectively. We obtain a solution for the case of a disk-shaped region with uniform zeta potential and show that the flow field created is an exact dipole, even in the immediate vicinity of the disk. In addition, we study the inverse problem where the desired flow field is known and solve for the zeta potential distribution required in order to establish it. Finally, we demonstrate that such inverse problem solutions can be used to create directional flows confined within narrow regions, without physical walls. Such solutions are equivalent to flow within channels and we show that these can be assembled to create complex microfluidic networks, composed of intersecting channels and turns, which are basic building blocks in microfluidic devices.

@article{
 title = {Current monitoring in a microchannel with repeated constrictions for accurate detection of sample location in isotachophoresis},
 type = {article},
 year = {2015},
 pages = {388-393},
 volume = {87},
 websites = {https://pubs.acs.org/doi/abs/10.1021/ac5036346},
 id = {91cd548c-58bf-3ccd-827b-cd65353d16c3},
 created = {2019-01-20T05:44:38.711Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.930Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present a new method for accurate detection of sample location in peak mode isotachophoresis (ITP). The technique is based on the design of a microchannel with multiple constrictions and on detecting the passage of the ITP interface through these constrictions. We achieve this by monitoring the electric current across the channel, which exhibits sharp decreases as the ITP interface moves more rapidly through the higher current density constrictions. We show that cross-correlation between the electric current signal and a predefined step function is an effective method for detecting changes in the slope of the electric current curve in real-time and is robust to changes in the composition of the buffers. We demonstrate the use of the technique to deliver sample to a designated location in the channel with an accuracy as low as 50 μm. Importantly, the method does not require the use of any optics and thus can be used to monitor the location of unlabeled species for application in a variety of ITP assays.},
 bibtype = {article},
 author = {Karsenty, Merav and Rosenfeld, Tally and Gommed, Khaled and Bercovici, Moran},
 doi = {10.1021/ac5036346},
 journal = {Analytical Chemistry},
 number = {1}
}

We present a new method for accurate detection of sample location in peak mode isotachophoresis (ITP). The technique is based on the design of a microchannel with multiple constrictions and on detecting the passage of the ITP interface through these constrictions. We achieve this by monitoring the electric current across the channel, which exhibits sharp decreases as the ITP interface moves more rapidly through the higher current density constrictions. We show that cross-correlation between the electric current signal and a predefined step function is an effective method for detecting changes in the slope of the electric current curve in real-time and is robust to changes in the composition of the buffers. We demonstrate the use of the technique to deliver sample to a designated location in the channel with an accuracy as low as 50 μm. Importantly, the method does not require the use of any optics and thus can be used to monitor the location of unlabeled species for application in a variety of ITP assays.

@article{
 title = {Diffusion dependent focusing regimes in peak mode counterflow isotachophoresis},
 type = {article},
 year = {2015},
 volume = {27},
 websites = {https://aip.scitation.org/doi/abs/10.1063/1.4927230},
 id = {ae80cb00-3832-3e29-9a06-775852aee57b},
 created = {2019-01-20T05:45:06.265Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.504Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present an analytical, numerical, and experimental study of pressure driven counterflow isotachophoresis (ITP). We study solutions to the Nernst-Planck equations in the axi-symmetric and radially dependent case, in the leading order of negligible body forces. We provide a simple model that describes the ITP interface shape for Poiseuille-type counterflows, and an asymptotic model which captures two distinct sample focusing regimes of peak mode ITP. We validate the existence of these regimes using numerical simulations and map the conditions under which each of the focal regions dominates. In particular, we demonstrate numerically that a species diffusivity is a key parameter determining its focusing regime. We experimentally show that this allows spatial separation of co-focusing species having distinctly different diffusivities. We further demonstrate that while dispersion associated with counterflow is typically considered to reduce peak concentrations, certain focusing regimes allow a net gain in sample concentration over the non-dispersed case.},
 bibtype = {article},
 author = {GanOr, Nethanel and Rubin, Shimon and Bercovici, Moran},
 doi = {10.1063/1.4927230},
 journal = {Physics of Fluids},
 number = {7}
}

We present an analytical, numerical, and experimental study of pressure driven counterflow isotachophoresis (ITP). We study solutions to the Nernst-Planck equations in the axi-symmetric and radially dependent case, in the leading order of negligible body forces. We provide a simple model that describes the ITP interface shape for Poiseuille-type counterflows, and an asymptotic model which captures two distinct sample focusing regimes of peak mode ITP. We validate the existence of these regimes using numerical simulations and map the conditions under which each of the focal regions dominates. In particular, we demonstrate numerically that a species diffusivity is a key parameter determining its focusing regime. We experimentally show that this allows spatial separation of co-focusing species having distinctly different diffusivities. We further demonstrate that while dispersion associated with counterflow is typically considered to reduce peak concentrations, certain focusing regimes allow a net gain in sample concentration over the non-dispersed case.

@article{
 title = {Acceleration of surface-based hybridization reactions using isotachophoretic focusing},
 type = {article},
 year = {2014},
 pages = {3028-3036},
 volume = {86},
 websites = {https://pubs.acs.org/doi/abs/10.1021/ac403838j},
 id = {1fcae5f1-435b-34c0-b612-40c1a2939572},
 created = {2019-01-20T05:28:08.308Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.295Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Karsenty},
 private_publication = {false},
 abstract = {We present a theoretical model and experimental demonstration of a novel method for acceleration of surface-based reactions using isotachophoresis (ITP). We use ITP to focus a sample of interest and deliver a high concentration target to a prefunctionalized surface, thus enabling rapid reaction at the sensor site. The concentration of the focused analyte is bound in space by the ITP interface and, upon reaction with the surface, continues electromigrating downstream, removing any contamination or reacted sample molecules from the surface. This constitutes a one-step react-and-wash assay which can be performed in a simple channel and does not require flow control elements or moving parts. We designed a novel microfluidic chip where reaction surfaces are formed by paramagnetic beads, immobilized at desired sites by an external magnetic field. Using this chip, we compared ITP-based surface hybridization to standard continuous flow-based hybridization and experimentally demonstrated a 2 orders of magnitude improvement in limit of detection (LoD) in a 3 min nucleic acid hybridization assay. The simple analytical model we present allows prediction of the rate of surface reaction under ITP and can be used to design and optimize such assays as a function of the physical properties of the system, including buffer chemistry, applied voltage, analyte mobility, analyte concentration, probe density, and surface length. The method, model, and experimental setup can be applied to various forms or surface reactions and may serve as the basis for highly genetic analysis and immunoassays.},
 bibtype = {article},
 author = {Karsenty, Merav and Rubin, Shimon and Bercovici, Moran},
 doi = {10.1021/ac403838j},
 journal = {Analytical Chemistry},
 number = {6}
}

We present a theoretical model and experimental demonstration of a novel method for acceleration of surface-based reactions using isotachophoresis (ITP). We use ITP to focus a sample of interest and deliver a high concentration target to a prefunctionalized surface, thus enabling rapid reaction at the sensor site. The concentration of the focused analyte is bound in space by the ITP interface and, upon reaction with the surface, continues electromigrating downstream, removing any contamination or reacted sample molecules from the surface. This constitutes a one-step react-and-wash assay which can be performed in a simple channel and does not require flow control elements or moving parts. We designed a novel microfluidic chip where reaction surfaces are formed by paramagnetic beads, immobilized at desired sites by an external magnetic field. Using this chip, we compared ITP-based surface hybridization to standard continuous flow-based hybridization and experimentally demonstrated a 2 orders of magnitude improvement in limit of detection (LoD) in a 3 min nucleic acid hybridization assay. The simple analytical model we present allows prediction of the rate of surface reaction under ITP and can be used to design and optimize such assays as a function of the physical properties of the system, including buffer chemistry, applied voltage, analyte mobility, analyte concentration, probe density, and surface length. The method, model, and experimental setup can be applied to various forms or surface reactions and may serve as the basis for highly genetic analysis and immunoassays.

@article{
 title = {Microfluidic assay for continuous bacteria detection using antimicrobial peptides and isotachophoresis},
 type = {article},
 year = {2014},
 pages = {10106-10113},
 volume = {86},
 websites = {https://pubs.acs.org/doi/abs/10.1021/ac5017776},
 id = {88133131-81ab-3d5a-aabb-8831b08d98b1},
 created = {2019-01-20T05:28:08.440Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.222Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Schwartz},
 private_publication = {false},
 abstract = {We present a novel microfluidic assay for continuous and quantitative detection of bacteria in water. We leverage isotachophoresis (ITP), an electrophoretic focusing technique, to create a stationary high concentration zone of fluorescently labeled antimicrobial peptides (AMPs) in a microfluidic channel. The tested water sample flows continuously through this high concentration AMPs reaction zone; any bacteria present in the sample is simultaneously labeled by, and separated from, the high concentration AMPs. The labeled bacteria continue into the downstream pure-buffer zone where the fluorescence signal is monitored, providing a direct quantitative measurement of the original bacterial concentration in the sample. We present the principles of the technique, demonstrate its applicability for quantitative detection of E. coli as well as its stability over a 1 h monitoring time, and provide a simple model for predicting its performance at different operating conditions. The method could be potentially expanded for use with other types of probes and provide continuous analysis and monitoring of water samples at the point of need.},
 bibtype = {article},
 author = {Schwartz, Ortal and Bercovici, Moran},
 doi = {10.1021/ac5017776},
 journal = {Analytical Chemistry},
 number = {20}
}

We present a novel microfluidic assay for continuous and quantitative detection of bacteria in water. We leverage isotachophoresis (ITP), an electrophoretic focusing technique, to create a stationary high concentration zone of fluorescently labeled antimicrobial peptides (AMPs) in a microfluidic channel. The tested water sample flows continuously through this high concentration AMPs reaction zone; any bacteria present in the sample is simultaneously labeled by, and separated from, the high concentration AMPs. The labeled bacteria continue into the downstream pure-buffer zone where the fluorescence signal is monitored, providing a direct quantitative measurement of the original bacterial concentration in the sample. We present the principles of the technique, demonstrate its applicability for quantitative detection of E. coli as well as its stability over a 1 h monitoring time, and provide a simple model for predicting its performance at different operating conditions. The method could be potentially expanded for use with other types of probes and provide continuous analysis and monitoring of water samples at the point of need.

@article{
 title = {1000-Fold Sample Focusing on Paper-Based Microfluidic Devices},
 type = {article},
 year = {2014},
 pages = {4465-4474},
 volume = {14},
 websites = {http://pubs.rsc.org/en/content/articlehtml/2014/lc/c4lc00734d},
 id = {6a4c1bfc-21e3-3a16-9a87-7fc2934cc128},
 created = {2019-01-20T05:44:25.392Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.393Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present an experimental and analytical study of a novel paper-based analytical device (μPAD) for isotachophoretic sample focusing. Guided by a simple heat transfer model, we further developed wax printing fabrication to enable the creation of shallow channels, which are critical in providing sufficient dissipation of Joule heat, and thus enable the use of high electric fields and short analysis time. This results in a device that is self-contained on a simple piece of filter paper and does not require any specialized enclosures or cooling devices to combat evaporation at high temperatures. Furthermore, we provide an analytical model for isotachophoretic sample accumulation in porous media, introduce a simple figure of merit for evaluating and comparing the efficiency of such devices, and present experimental validation in both paper and glass channels. Using this device we demonstrate the processing of 30 μL of sample achieving 1000-fold increase in peak concentration in 6 min. We believe that this method and device can serve as a guide to the design of low-cost, rapid and highly sensitive paper-based diagnostic platforms.},
 bibtype = {article},
 author = {Rosenfeld, Tally and Bercovici, Moran},
 doi = {10.1039/c4lc00734d},
 journal = {Lab on a Chip},
 number = {23}
}

We present an experimental and analytical study of a novel paper-based analytical device (μPAD) for isotachophoretic sample focusing. Guided by a simple heat transfer model, we further developed wax printing fabrication to enable the creation of shallow channels, which are critical in providing sufficient dissipation of Joule heat, and thus enable the use of high electric fields and short analysis time. This results in a device that is self-contained on a simple piece of filter paper and does not require any specialized enclosures or cooling devices to combat evaporation at high temperatures. Furthermore, we provide an analytical model for isotachophoretic sample accumulation in porous media, introduce a simple figure of merit for evaluating and comparing the efficiency of such devices, and present experimental validation in both paper and glass channels. Using this device we demonstrate the processing of 30 μL of sample achieving 1000-fold increase in peak concentration in 6 min. We believe that this method and device can serve as a guide to the design of low-cost, rapid and highly sensitive paper-based diagnostic platforms.

@article{
 title = {Sample distribution in peak mode isotachophoresis},
 type = {article},
 year = {2014},
 pages = {012001},
 volume = {26},
 websites = {http://aip.scitation.org/doi/10.1063/1.4861399},
 month = {1},
 id = {6a92ce21-76bb-390e-9d32-b0e059804b0b},
 created = {2019-01-20T05:44:38.291Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:13.017Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present an analytical study of peak mode isotachophoresis (ITP), and provide closed form solutions for sample distribution and electric field, as well as for leading-, trailing-, and counter-ion concentration profiles. Importantly, the solution we present is valid not only for the case of fully ionized species, but also for systems of weak electrolytes which better represent real buffer systems and for multivalent analytes such as proteins and DNA. The model reveals two major scales which govern the electric field and buffer distributions, and an additional length scale governing ana-lyte distribution. Using well-controlled experiments, and numerical simulations, we verify and validate the model and highlight its key merits as well as its limitations. We demonstrate the use of the model for determining the peak concentration of focused sample based on known buffer and analyte properties, and show it differs significantly from commonly used approximations based on the interface width alone. We further apply our model for studying reactions between multiple species having different effective mobilities yet co-focused at a single ITP interface. We find a closed form expression for an effective-on rate which depends on reactants distributions, and derive the conditions for optimizing such reactions. Interestingly, the model reveals that maximum reaction rate is not necessarily obtained when the concentration pro-files of the reacting species perfectly overlap. In addition to the exact solutions, we derive throughout several closed form engineering approximations which are based on elementary functions and are simple to implement, yet maintain the interplay between the important scales. Both the exact and approximate solutions provide in-sight into sample focusing and can be used to design and optimize ITP-based assays. C 2014 AIP Publishing LLC. [http://dx.},
 bibtype = {article},
 author = {Rubin, Shimon and Schwartz, Ortal and Bercovici, Moran},
 doi = {10.1063/1.4861399},
 journal = {Physics of Fluids},
 number = {1}
}

We present an analytical study of peak mode isotachophoresis (ITP), and provide closed form solutions for sample distribution and electric field, as well as for leading-, trailing-, and counter-ion concentration profiles. Importantly, the solution we present is valid not only for the case of fully ionized species, but also for systems of weak electrolytes which better represent real buffer systems and for multivalent analytes such as proteins and DNA. The model reveals two major scales which govern the electric field and buffer distributions, and an additional length scale governing ana-lyte distribution. Using well-controlled experiments, and numerical simulations, we verify and validate the model and highlight its key merits as well as its limitations. We demonstrate the use of the model for determining the peak concentration of focused sample based on known buffer and analyte properties, and show it differs significantly from commonly used approximations based on the interface width alone. We further apply our model for studying reactions between multiple species having different effective mobilities yet co-focused at a single ITP interface. We find a closed form expression for an effective-on rate which depends on reactants distributions, and derive the conditions for optimizing such reactions. Interestingly, the model reveals that maximum reaction rate is not necessarily obtained when the concentration pro-files of the reacting species perfectly overlap. In addition to the exact solutions, we derive throughout several closed form engineering approximations which are based on elementary functions and are simple to implement, yet maintain the interplay between the important scales. Both the exact and approximate solutions provide in-sight into sample focusing and can be used to design and optimize ITP-based assays. C 2014 AIP Publishing LLC. [http://dx.

@article{
 title = {Simulation tool coupling nonlinear electrophoresis and reaction kinetics for design and optimization of biosensors},
 type = {article},
 year = {2014},
 pages = {7835-7842},
 volume = {86},
 websites = {http://pubs.acs.org/doi/10.1021/ac5018953},
 month = {8},
 day = {5},
 id = {44910bde-ee1f-3443-a37a-3cf745d934a5},
 created = {2019-01-20T05:44:38.297Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.643Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present the development, formulation, validation, and demonstration of a fast, generic, and open source simulation tool, which integrates nonlinear electromigration with multispecies nonequilibrium kinetic reactions. The code is particularly useful for the design and optimization of new electrophoresis-based bioanlaytical assays, in which electrophoretic transport, separation, or focusing control analyte spatial concentration and subsequent reactions. By decoupling the kinetics solver from the electric field solver, we demonstrate an order of magnitude improvement in total simulation time for a series of 100 reaction simulations using a shared background electric field. The code can efficiently handle complex electrophoretic setups coupling sharp electric field gradients with bulk reactions, surface reactions, and competing reactions. For example, we demonstrate the use of the code for investigating accelerated reactions using isotachophoresis (ITP), revealing new regimes of operation which in turn ena...},
 bibtype = {article},
 author = {Dagan, Ofer and Bercovici, Moran},
 doi = {10.1021/ac5018953},
 journal = {Analytical Chemistry},
 number = {15}
}

We present the development, formulation, validation, and demonstration of a fast, generic, and open source simulation tool, which integrates nonlinear electromigration with multispecies nonequilibrium kinetic reactions. The code is particularly useful for the design and optimization of new electrophoresis-based bioanlaytical assays, in which electrophoretic transport, separation, or focusing control analyte spatial concentration and subsequent reactions. By decoupling the kinetics solver from the electric field solver, we demonstrate an order of magnitude improvement in total simulation time for a series of 100 reaction simulations using a shared background electric field. The code can efficiently handle complex electrophoretic setups coupling sharp electric field gradients with bulk reactions, surface reactions, and competing reactions. For example, we demonstrate the use of the code for investigating accelerated reactions using isotachophoresis (ITP), revealing new regimes of operation which in turn ena...

@article{
 title = {Rapid hybridization of nucleic acids using isotachophoresis},
 type = {article},
 year = {2012},
 pages = {11127-11132},
 volume = {109},
 websites = {http://www.pnas.org/cgi/doi/10.1073/pnas.1205004109},
 id = {d30ec6ce-1810-31bd-b7d9-bfa559c9fc83},
 created = {2019-01-20T05:44:25.215Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:17.988Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We use isotachophoresis (ITP) to control and increase the rate of nucleic acid hybridization reactions in free solution. We present a new physical model, validation experiments, and demonstrations of this assay. We studied the coupled physicochemical processes of preconcentration, mixing, and chemical reaction kinetics under ITP. Our experimentally validated model enables a closed form solution for ITP-aided reaction kinetics, and reveals a new characteristic time scale which correctly predicts order 10,000-fold speed-up of chemical reaction rate for order 100 pM reactants, and greater enhancement at lower concentrations. At 500 pM concentration, we measured a reaction time which is 14,000-fold lower than that predicted for standard second-order hybridization. The model and method are generally applicable to acceleration of reactions involving nucleic acids, and may be applicable to a wide range of reactions involving ionic reactants.},
 bibtype = {article},
 author = {Bercovici, M. and Han, C. M. and Liao, J. C. and Santiago, J. G.},
 doi = {10.1073/pnas.1205004109},
 journal = {Proceedings of the National Academy of Sciences},
 number = {28}
}

We use isotachophoresis (ITP) to control and increase the rate of nucleic acid hybridization reactions in free solution. We present a new physical model, validation experiments, and demonstrations of this assay. We studied the coupled physicochemical processes of preconcentration, mixing, and chemical reaction kinetics under ITP. Our experimentally validated model enables a closed form solution for ITP-aided reaction kinetics, and reveals a new characteristic time scale which correctly predicts order 10,000-fold speed-up of chemical reaction rate for order 100 pM reactants, and greater enhancement at lower concentrations. At 500 pM concentration, we measured a reaction time which is 14,000-fold lower than that predicted for standard second-order hybridization. The model and method are generally applicable to acceleration of reactions involving nucleic acids, and may be applicable to a wide range of reactions involving ionic reactants.

@article{
 title = {Robust and high-resolution simulations of nonlinear electrokinetic processes in variable cross-section channels},
 type = {article},
 year = {2012},
 keywords = {Electrokinetics,High-resolution,Quasi-1D model,Simulation,Variable cross-section},
 pages = {3036-3051},
 volume = {33},
 websites = {https://onlinelibrary.wiley.com/doi/abs/10.1002/elps.201200264},
 id = {d25820a1-7677-3565-8aa0-a6787dcdd453},
 created = {2019-01-20T05:44:38.492Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.947Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present a model and an associated numerical scheme to simulate complex electrokinetic processes in channels with nonuniform cross‐sectional area. We develop a quasi‐1D model based on local cross‐sectional area averaging of the equations describing unsteady, multispecies, electromigration‐diffusion transport. Our approach uses techniques of lubrication theory to approximate electrokinetic flows in channels with arbitrary variations in cross‐section; and we include chemical equilibrium calculations for weak electrolytes, Taylor–Aris type dispersion due of nonuniform bulk flow, and the effects of ionic strength on species mobility and on acid–base equilibrium constants. To solve the quasi‐1D governing equations, we provide a dissipative finite volume scheme that adds numerical dissipation at selective locations to ensure both unconditional stability and high accuracy. We couple the numerical scheme with a novel adaptive grid refinement algorithm that further improves the accuracy of simulations by minimizing numerical dissipation. We benchmark our numerical scheme with existing numerical schemes by simulating nonlinear electrokinetic problems, including ITP and electromigration dispersion in CZE. Simulation results show that our approach yields fast, stable, and high‐resolution solutions using an order of magnitude less grid points compared to the existing dissipative schemes. To highlight our model's capabilities, we demonstrate simulations that predict increase in detection sensitivity of ITP in converging cross‐sectional area channels. We also show that our simulations of ITP in variable cross‐sectional area channels have very good quantitative agreement with published experimental data.},
 bibtype = {article},
 author = {Bahga, Supreet S. and Bercovici, Moran and Santiago, Juan G.},
 doi = {10.1002/elps.201200264},
 journal = {Electrophoresis},
 number = {19-20}
}

We present a model and an associated numerical scheme to simulate complex electrokinetic processes in channels with nonuniform cross‐sectional area. We develop a quasi‐1D model based on local cross‐sectional area averaging of the equations describing unsteady, multispecies, electromigration‐diffusion transport. Our approach uses techniques of lubrication theory to approximate electrokinetic flows in channels with arbitrary variations in cross‐section; and we include chemical equilibrium calculations for weak electrolytes, Taylor–Aris type dispersion due of nonuniform bulk flow, and the effects of ionic strength on species mobility and on acid–base equilibrium constants. To solve the quasi‐1D governing equations, we provide a dissipative finite volume scheme that adds numerical dissipation at selective locations to ensure both unconditional stability and high accuracy. We couple the numerical scheme with a novel adaptive grid refinement algorithm that further improves the accuracy of simulations by minimizing numerical dissipation. We benchmark our numerical scheme with existing numerical schemes by simulating nonlinear electrokinetic problems, including ITP and electromigration dispersion in CZE. Simulation results show that our approach yields fast, stable, and high‐resolution solutions using an order of magnitude less grid points compared to the existing dissipative schemes. To highlight our model's capabilities, we demonstrate simulations that predict increase in detection sensitivity of ITP in converging cross‐sectional area channels. We also show that our simulations of ITP in variable cross‐sectional area channels have very good quantitative agreement with published experimental data.

@article{
 title = {Clinical Validation of Integrated Nucleic Acid and Protein Detection on an Electrochemical Biosensor Array for Urinary Tract Infection Diagnosis},
 type = {article},
 year = {2011},
 pages = {e26846},
 volume = {6},
 websites = {https://dx.plos.org/10.1371/journal.pone.0026846},
 month = {10},
 day = {31},
 id = {d10dd03f-1e8c-370b-939c-1b7bfaedfd7d},
 created = {2019-01-20T05:28:07.743Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.665Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Mohan2011},
 private_publication = {false},
 abstract = {Background Urinary tract infection (UTI) is a common infection that poses a substantial healthcare burden, yet its definitive diagnosis can be challenging. There is a need for a rapid, sensitive and reliable analytical method that could allow early detection of UTI and reduce unnecessary antibiotics. Pathogen identification along with quantitative detection of lactoferrin, a measure of pyuria, may provide useful information towards the overall diagnosis of UTI. Here, we report an integrated biosensor platform capable of simultaneous pathogen identification and detection of urinary biomarker that could aid the effectiveness of the treatment and clinical management. Methodology/Principal Findings The integrated pathogen 16S rRNA and host lactoferrin detection using the biosensor array was performed on 113 clinical urine samples collected from patients at risk for complicated UTI. For pathogen detection, the biosensor used sandwich hybridization of capture and detector oligonucleotides to the target analyte, bacterial 16S rRNA. For detection of the protein biomarker, the biosensor used an analogous electrochemical sandwich assay based on capture and detector antibodies. For this assay, a set of oligonucleotide probes optimized for hybridization at 37°C to facilitate integration with the immunoassay was developed. This probe set targeted common uropathogens including E. coli, P. mirabilis, P. aeruginosa and Enterococcus spp. as well as less common uropathogens including Serratia, Providencia, Morganella and Staphylococcus spp. The biosensor assay for pathogen detection had a specificity of 97% and a sensitivity of 89%. A significant correlation was found between LTF concentration measured by the biosensor and WBC and leukocyte esterase (p<0.001 for both). Conclusion/Significance We successfully demonstrate simultaneous detection of nucleic acid and host immune marker on a single biosensor array in clinical samples. This platform can be used for multiplexed detection of nucleic acid and protein as the next generation of urinary tract infection diagnostics.},
 bibtype = {article},
 author = {Mohan, Ruchika and Mach, Kathleen E and Bercovici, Moran and Pan, Ying and Dhulipala, Lakshmi and Kin, Pak and Liao, Joseph C},
 editor = {Wanunu, Meni},
 doi = {10.1371/journal.pone.0026846},
 journal = {PLoS ONE},
 number = {10}
}

Background Urinary tract infection (UTI) is a common infection that poses a substantial healthcare burden, yet its definitive diagnosis can be challenging. There is a need for a rapid, sensitive and reliable analytical method that could allow early detection of UTI and reduce unnecessary antibiotics. Pathogen identification along with quantitative detection of lactoferrin, a measure of pyuria, may provide useful information towards the overall diagnosis of UTI. Here, we report an integrated biosensor platform capable of simultaneous pathogen identification and detection of urinary biomarker that could aid the effectiveness of the treatment and clinical management. Methodology/Principal Findings The integrated pathogen 16S rRNA and host lactoferrin detection using the biosensor array was performed on 113 clinical urine samples collected from patients at risk for complicated UTI. For pathogen detection, the biosensor used sandwich hybridization of capture and detector oligonucleotides to the target analyte, bacterial 16S rRNA. For detection of the protein biomarker, the biosensor used an analogous electrochemical sandwich assay based on capture and detector antibodies. For this assay, a set of oligonucleotide probes optimized for hybridization at 37°C to facilitate integration with the immunoassay was developed. This probe set targeted common uropathogens including E. coli, P. mirabilis, P. aeruginosa and Enterococcus spp. as well as less common uropathogens including Serratia, Providencia, Morganella and Staphylococcus spp. The biosensor assay for pathogen detection had a specificity of 97% and a sensitivity of 89%. A significant correlation was found between LTF concentration measured by the biosensor and WBC and leukocyte esterase (p<0.001 for both). Conclusion/Significance We successfully demonstrate simultaneous detection of nucleic acid and host immune marker on a single biosensor array in clinical samples. This platform can be used for multiplexed detection of nucleic acid and protein as the next generation of urinary tract infection diagnostics.

@article{
 title = {High-sensitivity detection using isotachophoresis with variable cross-section geometry},
 type = {article},
 year = {2011},
 keywords = {Column coupling,Indirect detection,Isotachophoresis,Sensitivity,Volume coupling},
 pages = {563-572},
 volume = {32},
 websites = {https://onlinelibrary.wiley.com/doi/abs/10.1002/elps.201000338},
 id = {32b55d90-f30a-3a35-88d8-43f065183c56},
 created = {2019-01-20T05:44:25.531Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.636Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {We present a theoretical and experimental study on increasing the sensitivity of ITP assays by varying channel cross-section. We present a simple, unsteady, diffusion-free model for plateau mode ITP in channels with axially varying cross-section. Our model takes into account detailed chemical equilibrium calculations and handles arbitrary variations in channel cross-section. We have validated our model with numerical simulations of a more comprehensive model of ITP. We show that using strongly convergent channels can lead to a large increase in sensitivity and simultaneous reduction in assay time, compared to uniform cross-section channels. We have validated our theoretical predictions with detailed experiments by varying channel geometry and analyte concentrations. We show the effectiveness of using strongly convergent channels by demonstrating indirect fluorescence detection with a sensitivity of 100 nM. We also present simple analytical relations for dependence of zone length and assay time on geometric parameters of strongly convergent channels. Our theoretical analysis and experimental validations provide useful guidelines on optimizing chip geometry for maximum sensitivity under constraints of required assay time, chip area and power supply.},
 bibtype = {article},
 author = {Bahga, Supreet S. and Kaigala, Govind V. and Bercovici, Moran and Santiago, Juan G.},
 doi = {10.1002/elps.201000338},
 journal = {Electrophoresis},
 number = {5}
}

We present a theoretical and experimental study on increasing the sensitivity of ITP assays by varying channel cross-section. We present a simple, unsteady, diffusion-free model for plateau mode ITP in channels with axially varying cross-section. Our model takes into account detailed chemical equilibrium calculations and handles arbitrary variations in channel cross-section. We have validated our model with numerical simulations of a more comprehensive model of ITP. We show that using strongly convergent channels can lead to a large increase in sensitivity and simultaneous reduction in assay time, compared to uniform cross-section channels. We have validated our theoretical predictions with detailed experiments by varying channel geometry and analyte concentrations. We show the effectiveness of using strongly convergent channels by demonstrating indirect fluorescence detection with a sensitivity of 100 nM. We also present simple analytical relations for dependence of zone length and assay time on geometric parameters of strongly convergent channels. Our theoretical analysis and experimental validations provide useful guidelines on optimizing chip geometry for maximum sensitivity under constraints of required assay time, chip area and power supply.

@article{
 title = {Sample dispersion in isotachophoresis},
 type = {article},
 year = {2011},
 keywords = {MHD and electrohydrodynamics,microfluidics},
 volume = {679},
 id = {00b8157e-5b0b-3c36-bc1b-2d37e3721e3c},
 created = {2019-05-22T05:20:22.823Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-05-22T05:20:22.823Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {true},
 abstract = {We present an analytical, numerical and experimental study of advective dispersion in isotachophoresis (ITP). We analyse the dynamics of the concentration field of a focused analyte in peak mode ITP. The analyte distribution is subject to electromigration, diffusion and advective dispersion. Advective dispersion results from strong internal pressure gradients caused by non-uniform electro-osmotic flow (EOF). Analyte dispersion strongly affects the sensitivity and resolution of ITP-based assays. We perform axisymmetric time-dependent numerical simulations of fluid flow, diffusion and electromigration. We find that analyte properties contribute greatly to dispersion in ITP. Analytes with mobility values near those of the trailing (TE) or leading electrolyte (LE) show greater penetration into the TE or LE, respectively. Local pressure gradients in the TE and LE then locally disperse these zones of analyte penetration. Based on these observations, we develop a one-dimensional analytical model of the focused sample zone. We treat the LE, TE and LE-TE interface regions separately and, in each, assume a local Taylor-Aris-type effective dispersion coefficient. We also performed well-controlled experiments in circular capillaries, which we use to validate our simulations and analytical model. Our model allows for fast and accurate prediction of the area-averaged sample distribution based on known parameters including species mobilities, EO mobility, applied current density and channel dimensions. This model elucidates the fundamental mechanisms underlying analyte advective dispersion in ITP and can be used to optimize detector placement in detection-based assays. © 2011 Cambridge University Press.},
 bibtype = {article},
 author = {Garcia-Schwarz, G. and Bercovici, M. and Marshall, L.A. and Santiago, J.G.},
 doi = {10.1017/jfm.2011.139},
 journal = {Journal of Fluid Mechanics}
}

We present an analytical, numerical and experimental study of advective dispersion in isotachophoresis (ITP). We analyse the dynamics of the concentration field of a focused analyte in peak mode ITP. The analyte distribution is subject to electromigration, diffusion and advective dispersion. Advective dispersion results from strong internal pressure gradients caused by non-uniform electro-osmotic flow (EOF). Analyte dispersion strongly affects the sensitivity and resolution of ITP-based assays. We perform axisymmetric time-dependent numerical simulations of fluid flow, diffusion and electromigration. We find that analyte properties contribute greatly to dispersion in ITP. Analytes with mobility values near those of the trailing (TE) or leading electrolyte (LE) show greater penetration into the TE or LE, respectively. Local pressure gradients in the TE and LE then locally disperse these zones of analyte penetration. Based on these observations, we develop a one-dimensional analytical model of the focused sample zone. We treat the LE, TE and LE-TE interface regions separately and, in each, assume a local Taylor-Aris-type effective dispersion coefficient. We also performed well-controlled experiments in circular capillaries, which we use to validate our simulations and analytical model. Our model allows for fast and accurate prediction of the area-averaged sample distribution based on known parameters including species mobilities, EO mobility, applied current density and channel dimensions. This model elucidates the fundamental mechanisms underlying analyte advective dispersion in ITP and can be used to optimize detector placement in detection-based assays. © 2011 Cambridge University Press.

@article{
 title = {Rapid detection of urinary tract infections using isotachophoresis and molecular beacons},
 type = {article},
 year = {2011},
 volume = {83},
 id = {14cb8ede-798c-3e5b-aff5-f23a73981027},
 created = {2019-05-22T05:20:23.010Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-05-22T05:20:23.010Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {true},
 abstract = {We present a novel assay for rapid detection and identification of bacterial urinary tract infections using isotachophoresis (ITP) and molecular beacons. We applied on-chip ITP to extract and focus 16S rRNA directly from bacterial lysate and used molecular beacons to achieve detection of bacteria specific sequences. We demonstrated detection of E. coli in bacteria cultures as well as in patient urine samples in the clinically relevant range 1E6-1E8 cfu/mL. For bacterial cultures we further demonstrate quantification in this range. The assay requires minimal sample preparation (a single centrifugation and dilution), and can be completed, from beginning of lysing to detection, in under 15 min. We believe that the principles presented here can be used for design of other rapid diagnostics or detection methods for pathogenic diseases. © 2011 American Chemical Society.},
 bibtype = {article},
 author = {Bercovici, M. and Kaigala, G.V. and MacH, K.E. and Han, C.M. and Liao, J.C. and Santiago, J.G.},
 doi = {10.1021/ac200253x},
 journal = {Analytical Chemistry},
 number = {11}
}

We present a novel assay for rapid detection and identification of bacterial urinary tract infections using isotachophoresis (ITP) and molecular beacons. We applied on-chip ITP to extract and focus 16S rRNA directly from bacterial lysate and used molecular beacons to achieve detection of bacteria specific sequences. We demonstrated detection of E. coli in bacteria cultures as well as in patient urine samples in the clinically relevant range 1E6-1E8 cfu/mL. For bacterial cultures we further demonstrate quantification in this range. The assay requires minimal sample preparation (a single centrifugation and dilution), and can be completed, from beginning of lysing to detection, in under 15 min. We believe that the principles presented here can be used for design of other rapid diagnostics or detection methods for pathogenic diseases. © 2011 American Chemical Society.

@article{
 title = {Ionic strength effects on electrophoretic focusing and separations: supplementary material},
 type = {article},
 year = {2010},
 volume = {31},
 websites = {https://onlinelibrary.wiley.com/doi/abs/10.1002/elps.200900560},
 id = {32831bb4-f22c-33bd-826b-f5b5b901abc2},
 created = {2019-01-20T05:28:08.138Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:12.864Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {Bahgaa},
 private_publication = {false},
 abstract = {We present a numerical and experimental study of the effects of ionic strength on electrophoretic focusing and separations. We review the development of ionic strength models for electrophoretic mobility and chemical activity and highlight their differences in the context of electrophoretic separation and focusing simulations. We couple a fast numerical solver for electrophoretic transport with the Onsager–Fuoss model for actual ionic mobility and the extended Debye–Huckle theory for correction of ionic activity. Model predictions for fluorescein mobility as a function of ionic strength and pH compare well with data from CZE experiments. Simulation predictions of preconcentration factors in peak mode ITP also compare well with the published experimental data. We performed ITP experiments to study the effect of ionic strength on the simultaneous focusing and separation. Our comparisons of the latter data with simulation results at 10 and 250 mM ionic strength show the model is able to capture the observed qualitative differences in ITP analyte zone shape and order. Finally, we present simulations of CZE experiments where changes in the ionic strength result in significant change in selectivity and order of analyte peaks. Our simulations of ionic strength effects in capillary electrophoresis compare well with the published experimental data.},
 bibtype = {article},
 author = {Bahga, Supreet S and Bercovici, Moran and Santiago, Juan G},
 journal = {Electrophoresis},
 number = {5}
}

We present a numerical and experimental study of the effects of ionic strength on electrophoretic focusing and separations. We review the development of ionic strength models for electrophoretic mobility and chemical activity and highlight their differences in the context of electrophoretic separation and focusing simulations. We couple a fast numerical solver for electrophoretic transport with the Onsager–Fuoss model for actual ionic mobility and the extended Debye–Huckle theory for correction of ionic activity. Model predictions for fluorescein mobility as a function of ionic strength and pH compare well with data from CZE experiments. Simulation predictions of preconcentration factors in peak mode ITP also compare well with the published experimental data. We performed ITP experiments to study the effect of ionic strength on the simultaneous focusing and separation. Our comparisons of the latter data with simulation results at 10 and 250 mM ionic strength show the model is able to capture the observed qualitative differences in ITP analyte zone shape and order. Finally, we present simulations of CZE experiments where changes in the ionic strength result in significant change in selectivity and order of analyte peaks. Our simulations of ionic strength effects in capillary electrophoresis compare well with the published experimental data.

@article{
 title = {Compact adaptive-grid scheme for high numerical resolution simulations of isotachophoresis},
 type = {article},
 year = {2010},
 keywords = {Adaptive grid,Chemical equilibrium,Compact scheme,Displacement electrophoresis,Electrokinetics,Electrophoresis,Isotachophoresis},
 pages = {588-599},
 volume = {1217},
 websites = {https://www.sciencedirect.com/science/article/pii/S0021967309017592},
 id = {6f254f1f-1524-34a4-b578-94444a8442a2},
 created = {2019-01-20T05:44:25.540Z},
 accessed = {2019-01-19},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T01:48:18.889Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {In a previous publication we demonstrated a fast simulation tool for solution of electrophoretic focusing and separation. We here describe the novel mathematical model and numerical algorithms used to create this code. These include the representation of advection-diffusion equations on an adaptive grid, high-resolution discretization of the equations (sixth order compact), a new variational-based approach for controlling the motion of grid points, and new boundary conditions which enable solution in a moving frame of reference. We discuss the advantages of combining a high-resolution discretization with an adaptive grid in accurately resolving sharp interfaces in isotachophoresis, and provide verification against known analytical solutions and comparison with prevailing exiting numerical algorithms. © 2009 Elsevier B.V. All rights reserved.},
 bibtype = {article},
 author = {Bercovici, Moran and Lele, Sanjiva K. and Santiago, Juan G.},
 doi = {10.1016/j.chroma.2009.11.072},
 journal = {Journal of Chromatography A},
 number = {4}
}

In a previous publication we demonstrated a fast simulation tool for solution of electrophoretic focusing and separation. We here describe the novel mathematical model and numerical algorithms used to create this code. These include the representation of advection-diffusion equations on an adaptive grid, high-resolution discretization of the equations (sixth order compact), a new variational-based approach for controlling the motion of grid points, and new boundary conditions which enable solution in a moving frame of reference. We discuss the advantages of combining a high-resolution discretization with an adaptive grid in accurately resolving sharp interfaces in isotachophoresis, and provide verification against known analytical solutions and comparison with prevailing exiting numerical algorithms. © 2009 Elsevier B.V. All rights reserved.

@article{
 title = {Fluorescent carrier ampholytes assay for portable, Label-Free detection of chemical toxins in tap water},
 type = {article},
 year = {2010},
 pages = {1858-1866},
 volume = {82},
 websites = {https://pubs.acs.org/doi/abs/10.1021/ac902526g%0A},
 publisher = {ACS Publications},
 id = {5599113e-31ae-30e8-82af-e6c0b55fc0e9},
 created = {2019-01-20T06:08:16.521Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:13.269Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {bercovici2010fluorescent},
 source_type = {article},
 private_publication = {false},
 abstract = {We present a novel method for fluorescence-based indirect detection of analytes and demonstrate its use for label-free detection of chemical toxins in a hand-held device. We fluorescently label a mixture of low-concentration carrier ampholytes and introduce it into an isotachophoresis (ITP) separation. The carrier ampholytes provide a large number of fluorescent species with a wide range of closely spaced effective electrophoretic mobilities. Analytes focus under ITP and displace subsets of these carrier ampholytes. The analytes are detected indirectly and quantified by analyzing the gaps in the fluorescent ampholyte signal. The large number (on the order of 1000) of carrier ampholytes enables detection of a wide range of analytes, requiring little a priori knowledge of their electrophoretic properties. We discuss the principles of the technique and demonstrate its use in the detection of various analytes using a standard microscope system. We then present the integration of the technique into a self-contained hand-held device and demonstrate detection of chemical toxins (2-nitrophenol and 2,4,6-trichlorophenol) in tap water, with no sample preparation steps.},
 bibtype = {article},
 author = {Beroovici, M. and Kaigala, G. V. and Baokhouse, C. J. and Santiago, J. G.},
 doi = {10.1021/ac902526g},
 journal = {Analytical Chemistry},
 number = {5}
}

We present a novel method for fluorescence-based indirect detection of analytes and demonstrate its use for label-free detection of chemical toxins in a hand-held device. We fluorescently label a mixture of low-concentration carrier ampholytes and introduce it into an isotachophoresis (ITP) separation. The carrier ampholytes provide a large number of fluorescent species with a wide range of closely spaced effective electrophoretic mobilities. Analytes focus under ITP and displace subsets of these carrier ampholytes. The analytes are detected indirectly and quantified by analyzing the gaps in the fluorescent ampholyte signal. The large number (on the order of 1000) of carrier ampholytes enables detection of a wide range of analytes, requiring little a priori knowledge of their electrophoretic properties. We discuss the principles of the technique and demonstrate its use in the detection of various analytes using a standard microscope system. We then present the integration of the technique into a self-contained hand-held device and demonstrate detection of chemical toxins (2-nitrophenol and 2,4,6-trichlorophenol) in tap water, with no sample preparation steps.

@article{
 title = {Method for Analyte Identification Using Isotachophoresis and a Fluorescent Carrier Ampholyte Assay},
 type = {article},
 year = {2010},
 pages = {2134-2138},
 volume = {82},
 websites = {https://pubs.acs.org/doi/abs/10.1021/ac9025658%0A},
 publisher = {ACS Publications},
 id = {bfe58c04-b2a8-324a-8913-8960499a725d},
 created = {2019-01-20T06:08:17.120Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:16:13.082Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {bercovici2010method},
 source_type = {article},
 private_publication = {false},
 abstract = {We present a novel method for identification of unlabeled analytes using fluorescent carrier ampholytes and isotachophoresis (ITP). The method is based on previous work where we showed that the ITP displacement of carrier ampholytes can be used for detection of unlabeled (nonfluorescent) analytes. We here propose a signal analysis method based on integration of the associated fluorescent signal. We define a normalized signal integral which is equivalent to an accurate measure of the amount of carrier ampholytes which are focused between the leading electrolyte and the analyte. We show that this parameter can be related directly to analyte effective mobility. Using several well characterized analytes, we construct calibration curves relating effective mobility and carrier ampholyte displacement at two different leading electrolyte (LE) buffers. On the basis of these calibration curves, we demonstrate the extraction of fully ionized mobility and dissociation constant of 2-nitrophenol and 2,4,6-trichlorophenol from ITP experiments with fluorescent carrier ampholytes. This extraction is based on no a priori assumptions or knowledge of these two toxic chemicals. This technique allows simultaneous identification of multiple analytes by their physiochemical properties in a few minutes and with no sample preparation.},
 bibtype = {article},
 author = {Bercovici, M and Kaigala, G V and Santiago, J G},
 journal = {Analytical chemistry},
 number = {5}
}

We present a novel method for identification of unlabeled analytes using fluorescent carrier ampholytes and isotachophoresis (ITP). The method is based on previous work where we showed that the ITP displacement of carrier ampholytes can be used for detection of unlabeled (nonfluorescent) analytes. We here propose a signal analysis method based on integration of the associated fluorescent signal. We define a normalized signal integral which is equivalent to an accurate measure of the amount of carrier ampholytes which are focused between the leading electrolyte and the analyte. We show that this parameter can be related directly to analyte effective mobility. Using several well characterized analytes, we construct calibration curves relating effective mobility and carrier ampholyte displacement at two different leading electrolyte (LE) buffers. On the basis of these calibration curves, we demonstrate the extraction of fully ionized mobility and dissociation constant of 2-nitrophenol and 2,4,6-trichlorophenol from ITP experiments with fluorescent carrier ampholytes. This extraction is based on no a priori assumptions or knowledge of these two toxic chemicals. This technique allows simultaneous identification of multiple analytes by their physiochemical properties in a few minutes and with no sample preparation.

@article{
 title = {Miniaturized system for isotachophoresis assays},
 type = {article},
 year = {2010},
 pages = {2242-2250},
 volume = {10},
 websites = {https://pubs.rsc.org/en/content/articlelanding/2010/lc/c004120c/unauth#!divAbstract%0A},
 publisher = {Royal Society of Chemistry},
 id = {8679f2c2-0ad2-32b1-b29b-76401a8726dc},
 created = {2019-01-20T06:08:17.951Z},
 file_attached = {false},
 profile_id = {dc1fdcdf-637d-32ee-a353-6a1d76918405},
 last_modified = {2019-01-27T02:09:15.883Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 citation_key = {kaigala2010miniaturized},
 source_type = {article},
 private_publication = {false},
 bibtype = {article},
 author = {Kaigala, G V and Bercovici, M and Behnam, M and Elliott, D and Santiago, J G and Backhouse, C J},
 journal = {Lab on a Chip},
 number = {17}
}

@article{
 title = {Open source simulation tool for electrophoretic stacking, focusing, and separation},
 type = {article},
 year = {2009},
 keywords = {Adaptive grid,Dispersion,Electrophoresis,High resolution,Isotachophoresis,Simulation},
 pages = {1008-1018},
 volume = {1216},
 websites = {https://www.sciencedirect.com/science/article/pii/S0021967308021535},
 id = {7eb32e86-ca1d-3044-829c-815f49bb8690},
 created = {2019-01-20T05:44:25.204Z},
 accessed = {2019-01-19},
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 abstract = {We present the development, formulation, and performance of a new simulation tool for electrophoretic preconcentration and separation processes such as capillary electrophoresis, isotachophoresis, and field amplified sample stacking. The code solves the one-dimensional transient advection-diffusion equations for multiple multivalent weak electrolytes (including ampholytes) and includes a model for pressure-driven flow and Taylor-Aris dispersion. The code uses a new approach for the discretization of the equations, consisting of a high resolution compact scheme which is combined with an adaptive grid algorithm. We show that this combination allows for accurate resolution of sharp concentration gradients at high electric fields, while at the same time significantly reducing the computational time. We demonstrate smooth, stable, and accurate solutions at current densities as high as 5000 A/m2 using only 300 grid points, and a 75-fold reduction in computational time compared with equivalent uniform grid techniques. The code is available as an open source for free at http://microfluidics.stanford.edu. © 2008 Elsevier B.V. All rights reserved.},
 bibtype = {article},
 author = {Bercovici, Moran and Lele, Sanjiva K. and Santiago, Juan G.},
 doi = {10.1016/j.chroma.2008.12.022},
 journal = {Journal of Chromatography A},
 number = {6}
}

We present the development, formulation, and performance of a new simulation tool for electrophoretic preconcentration and separation processes such as capillary electrophoresis, isotachophoresis, and field amplified sample stacking. The code solves the one-dimensional transient advection-diffusion equations for multiple multivalent weak electrolytes (including ampholytes) and includes a model for pressure-driven flow and Taylor-Aris dispersion. The code uses a new approach for the discretization of the equations, consisting of a high resolution compact scheme which is combined with an adaptive grid algorithm. We show that this combination allows for accurate resolution of sharp concentration gradients at high electric fields, while at the same time significantly reducing the computational time. We demonstrate smooth, stable, and accurate solutions at current densities as high as 5000 A/m2 using only 300 grid points, and a 75-fold reduction in computational time compared with equivalent uniform grid techniques. The code is available as an open source for free at http://microfluidics.stanford.edu. © 2008 Elsevier B.V. All rights reserved.