Abstract: Described herein is a bias-free high-throughput and high-yield continuous isoelectric fractionation (CIF) nanocarrier fractionation technique based on distinct isoelectric points. The nanocarrier fractionation platform is enabled by a robust and tunable linear pH profile provided by water-splitting at a bipolar membrane and stabilized by flow without ampholytes.

Abstract: Described herein is a bifurcated continuous field-flow fractionation (BCFFF) chip for high-yield and high-throughput nucleic acid extraction and purification. BCFFF uses a membrane ionic transistor to sustain low-ionic strength in a localized region at a junction, such that the resulting high field can selectively isolate high-charge density nucleic acids from the main flow channel and insert them into a standardized buffer in a side channel that bifurcates from the junction. The BCFFF platform can be used for isolation of both long dsDNAs and short miRNAs, without changing the device configuration or the operation protocol. BCFFF results in high-efficiency (>85%) concentration-independent DNA extraction and 40% net qRT-PCR miRNA yield from plasma, which is significantly higher than any other commercial liquid and solid extraction technologies.

Abstract: The invention provides an alternating current electrospray technology that can generate micron sized droplets in oil at very high throughput for emulsion or digital PCR (Polymerase Chain Reaction). This technology outperforms the throughput of the current gold standard in droplet generation using flow-focusing technology by at least a factor of 100. The design is simple and can generate a billion to a trillion monodispersed droplets in about one hour. This is much faster than flow-focusing which is limited to a few million droplets per hour. The droplet size and generation rate can also be easily adjusted by changing the voltage of the AC electric field. The range of produced droplet sizes is about 1-100 microns, wherein the droplets are monodispersed in size.

Abstract: Systems and methods for controlling molecular translocation in solid-state nanopores by edge field leakage. The system dramatically reduces (by orders of magnitude) and controls the fast electrophoretic velocity of molecules to realize sensitive and selective solid-state nanopore sensors for polynucleotides and sequencing platforms.

Abstract: Disclosed are methods, compositions, and devices for an integrated, heterogeneous ion-exchange membrane-based plastic microfluidic biochip platform that can be used to detect multiple diagnostic markers present in real samples. Its various components can be easily integrated in a modular fashion for different applications. Automated control allows sequential and dynamic activation of different components on the chip. The integrated platform consists of three units and is designed to execute the following functions: (i) separation of the target biomolecules from the real sample, (ii) localizing and concentrating the targeted molecules at a specific location in the microfluidic chip, and (iii) detection of the targeted molecules using hybridization/docking events against a complementary ssDNA oligoprobe sequence or a specific antibody.

Abstract: Exosomes carry microRNA biomarkers, occur in higher abundance in cancerous patients than in healthy ones, and because they are present in most biofluids, including blood and urine, can be obtained non-invasively. Standard laboratory techniques to isolate exosomes are expensive, time-consuming, provide poor purity, and recover on the order of 25% of the available exosomes. We present a new microfluidic technique to simultaneously isolate exosomes and preconcentrate them by electrophoresis using a high transverse local electric field generated by ion-depleting ion-selective membrane. We use pressure-driven flow to deliver an exosome sample to a microfluidic chip such that the transverse electric field forces them out of the cross flow and into an agarose gel which filters out unwanted cellular debris while the ion-selective membrane concentrates the exosomes through an enrichment effect. We efficiently isolated exosomes from 1×PBS buffer, cell culture media and blood serum.

Abstract: A nanoscale protein-sensing platform with a non-equilibrium on-off switch that employs dielectrophoretic and hydrodynamic shear forces to overcome these thermodynamic limitations with irreversible kinetics. The detection sensitivity is achieved with complete association of the antibody-antigen-antibody (Ab-Ag-Ab) complex by precisely and rapidly assembling carbon nanotubes (CNT) across two parallel electrodes via sequential DC electrophoresis and dielectrophoresis (DEP), and with single-CNT electron tunneling conductance. The high selectivity is achieved with a critical hydrodynamic shear rate between the activated dissociation shear rates of target and non-target linkers of the aligned CNTs.

Abstract: Described are methods for detecting and quantifying biomolecules such as polynucleotides or polypeptides in an electrophoresis matrix using ion concentration polarization and nanoparticle aggregation.

Abstract: Systems and methods for controlling molecular translocation in solid-state nanopores by edge field leakage. The system dramatically reduces (by orders of magnitude) and controls the fast electrophoretic velocity of molecules to realize sensitive and selective solid-state nanopore sensors for polynucleotides and sequencing platforms.

Abstract: Disclosed are methods, compositions, and devices for an integrated, heterogeneous ion-exchange membrane-based plastic microfluidic biochip platform that can be used to detect multiple diagnostic markers present in real samples. Its various components can be easily integrated in a modular fashion for different applications. Automated control allows sequential and dynamic activation of different components on the chip. The integrated platform consists of three units and is designed to execute the following functions: (i) separation of the target biomolecules from the real sample, (ii) localizing and concentrating the targeted molecules at a specific location in the microfluidic chip, and (iii) detection of the targeted molecules using hybridization/docking events against a complementary ssDNA oligoprobe sequence or a specific antibody.

Abstract: A DNA/RNA detection technology is provided. The open flow detection technique includes a substrate defining a pair of opposing microchannels, a pair of opposing electrodes in the opposing microchannels, and at least one ion exchanging nanomembrane coupled between the opposing microchannels such that the opposing microchannels are connected to each other only through the nanomembrane, wherein the nanomembrane is functionalized with a probe complementary to the macromolecule. A voltammeter is provided to measure the electrical current or potential across the nanomembrane, and detect a change in the measured electrical current or potential to quantify the presence of the macromolecule.

Abstract: The invention provides an alternating current electrospray technology that can generate micron sized droplets in oil at very high throughput for emulsion or digital PCR (Polymerase Chain Reaction). This technology outperforms the throughput of the current gold standard in droplet generation using flow-focusing technology by at least a factor of 100. The design is simple and can generate a billion to a trillion monodispersed droplets in about one hour. This is much faster than flow-focusing which is limited to a few million droplets per hour. The droplet size and generation rate can also be easily adjusted by changing the voltage of the AC electric field. The range of produced droplet sizes is about 1-100 microns, wherein the droplets are monodispersed in size.

Abstract: Disclosed are methods, compositions, and devices for an integrated, heterogenerous ion-exchange membrane-based plastic microfluidic biochip platform that can be used to detect multiple diagnostic markers present in real samples. Its various components can be easily integrated in a modular fashion for different applications. Automated control allows sequential and dynamic activation of different components on the chip. The integrated platform consists of three units and is designed to execute the following functions: (i) separation of the target biomolecules from the real sample, (ii) localizing and concentrating the targeted molecules at a specific location in the microfluidic chip, and (iii) detection of the targeted molecules using hybridization/docking events against a complementary ssDNA oligoprobe sequence or a specific antibody.

Abstract: Described are methods for detecting and quantifying biomolecules such as polynucleotides or polypeptides in an electrophoresis matrix using ion concentration polarization and nanoparticle aggregation.

Abstract: A nanoscale protein-sensing platform with a non-equilibrium on-off switch that employs dielectrophoretic and hydrodynamic shear forces to overcome these thermodynamic limitations with irreversible kinetics. The detection sensitivity is achieved with complete association of the antibody-antigen-antibody (Ab-Ag-Ab) complex by precisely and rapidly assembling carbon nanotubes (CNT) across two parallel electrodes via sequential DC electrophoresis and dielectrophoresis (DEP), and with single-CNT electron tunneling conductance. The high selectivity is achieved with a critical hydrodynamic shear rate between the activated dissociation shear rates of target and non-target linkers of the aligned CNTs.

Abstract: A nanopipette biosensor capable of detecting a small concentration of target molecules within a sample solution using optical detection methods. The biosensor includes a nanopipette that connects a nanocolloid reservoir containing a nanocolloid solution and a sample reservoir containing a sample solution, where the nanopipette is tapered at the end connected to the sample reservoir. The nanocolloid solution includes nanoparticles functionalized with probes specific to miRNA of the target molecules and reporters. During the detection process, the nanocolloids nanoparticles aggregate such that plasmonic hotspots are formed. These hotspots magnify the reporter signals produced when the probes hybridize with target molecules.

Abstract: Disclosed are methods, compositions, and devices for an integrated, heterogenerous ion-exchange membrane-based plastic microfluidic biochip platform that can be used to detect multiple diagnostic markers present in real samples. Its various components can be easily integrated in a modular fashion for different applications. Automated control allows sequential and dynamic activation of different components on the chip. The integrated platform consists of three units and is designed to execute the following functions: (i) separation of the target biomolecules from the real sample, (ii) localizing and concentrating the targeted molecules at a specific location in the microfluidic chip, and (iii) detection of the targeted molecules using hybridization/docking events against a complementary ssDNA oligo-probe sequence or a specific antibody.

Abstract: A DNA/RNA detection technology is provided. The open flow detection technique includes a substrate defining a pair of opposing microchannels, a pair of opposing electrodes in the opposing microchannels, and at least one ion exchanging nanomembrane coupled between the opposing microchannels such that the opposing microchannels are connected to each other only through the nanomembrane, wherein the nanomembrane is functionalized with a probe complementary to the macromolecule.

Abstract: A microchamber electrochemical cell and method of using the cell for performing quantitative analysis of various charged macromolecules is presented. The microchamber electrochemical cell includes a substrate, opposing electrodes and at least one nanoslot. The substrate is configured to define a pair of opposing fluid reservoirs. The pair of opposing electrodes are respectively positioned within the opposing fluid reservoirs. Each nanoslot is configured to fluidly connect the opposing fluid reservoirs together. The opposing fluid reservoirs of the microchamber electrochemical cell are fluidly connected to each other only through each nanoslot. Each nanoslot is physically restricted to less than 500 nanometers. One method includes the steps of coupling, filling, measuring, obtaining, performing and preparing.

Abstract: A nanopipette biosensor capable of detecting a small concentration of target molecules within a sample solution using optical detection methods. The biosensor includes a nanopipette that connects a nanocolloid reservoir containing a nanocolloid solution and a sample reservoir containing a sample solution, where the nanopipette is tapered at the end connected to the sample reservoir. The nanocolloid solution includes nanoparticles functionalized with probes specific to miRNA of the target molecules and reporters. During the detection process, the nanocolloids nanoparticles aggregate such that plasmonic hotspots are formed. These hotspots magnify the reporter signals produced when the probes hybridize with target molecules.