US Patent US11293057 Licensed to Aopia Biosciences

An AC field is used to generate monodispersed droplets at high throughput (1 kHz). The droplet generation does not require sheath flow of the external continuous flow and the need for a precision micropump. Its droplet size can also be tuned from 10 microns to hundreds of microns by simply adjusting the amplitude of the AC voltage. This tunability allows generation of small droplets when large droplet number (~1 million) is required to detect mutants from the background of wild types. The small droplet size allows for easy imaging of the large number of droplets with inexpensive imaging facility with small field of view. Imaging with low-cost camera is also enabled with larger droplets (hundreds of microns) for low copy number such as detecting down to 10 virus RNAs per ml. The same versatility allows for single-cell assay and single-cell encapsulation with fluids of different viscosity, elasticity and surface tension.

US Patent US11162935

A solid-state (polymer) conic nanopore technology with large pore radius (50 to 500 nm) and long-range field penetration allows high throughput detection of individual molecules. High-permittivity dielectric coating allows field leakage at the tip, such that flexible molecules like RNA can be pinned to the corner during entry from the tip side. Rigid molecules like RNA complexes would not be pinned and hence would exhibit a translocation time that is 100x faster. One can hence identify and quantify specific RNAs by hybridizing them with oligos. The technology is the only nanopore technology that can quantify 100 to 1 million copies (fM to pM) of specific RNA in realistic clinical samples. With nanoparticle reporters functionalized to antibodies, the technology can also quantify specific proteins from their translocation signatures

US Patent US10983035

Exosomes are isolated electrophoretically from a flowing plasma stream on a chip by using the high electric field in an ion-free region that is created by ion-depletion action of an on-chip ion-selective membrane. The field drives the exosomes transversely into a gel reservoir for latter collection or further on-chip analysis. It has a much higher yield than Ultra-Centrifugation and can be easily integrated with downstream assays like magnetic bead immunocapture, RNA extraction and quantification.

US Patent US10955380

A DC/AC protocol is invented to assemble Carbon Nanotubes (CNT) across an electrode pair rapidly and irreversibly. The CNTs and electrodes are functionalized by probes, using the target molecule as a link in a sandwitch scheme. The large hydrodynamic drag of the high-aspect ratio allows shear to remove non-specifically bound CNTs. The result is a very sensitive and selective sensor, capable of differentiating isoforms from target proteins with comparable dissociation constants and reducing the detection to 10 fM, orders of magnitude below the antibody-antigen dissociation constant.

US Patent US10669572

An electric field in a gel packs nanoparticles and molecules at an ion-selective membrane to achieve high association rate. Upon reversal of the field, the membrane depletes the ion in the gel and the resulting high field can precipitate target-tehered nanoparticles while removing the unlinked nanoparticles. Different particles precipitate at different locations to allow multi-target, rapid and sensitive detection. The high-field in the ion depleted region also break up non-specifically bound nanoparticles to reduce false positives.

US Patent US10247720 (2019) P01116 (2015) and licensed to AgenDx LLC

Charged molecules and ions can be concentrated a-million fold for easier detection by exploiting internal and external concentration polarization of nanoporous granule/membrane/nanoslot to electrophoretically and dielectrophoretically accumulate the analyte. Molecules can be isolated and separated by the high field of the depletion action. They can also be concentrated at a specific position by controlling the depletion front with an applied voltage.

US Patent US10557820 P01010 (2016) and licensed to AgenDx LLC

Charge inversion upon hybridization onto probes on permselective membrane is used for selective and sensitive nucleic acid detection. Ion depletion from the membrane surface in the limiting and overlimiting regions allows small change in surface charge to sensitively gate the ion current to achieve large (> 100 mV) voltage shifts. Although charge-based, it is not sensitive to variable screening due to different bulk ionic strengths because of the ion depletion action. The microvortices near the surface also endow specificity by its washing action.

US patent US9856518 (2014)

Dancon, 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.

US Patent US8969007 (2010)

We use a nanoslot to achieve on-chip ionic strength and pH control and to concentrate nanoparticles or macromolecules for sensing applications. The nanoparticles can be functionalized with probes such that their dielectrophoretic mobility change upon functionalization, thus achieving preferential trapping and quantification of hybridized nanoparticles.

US Patent US8716675 (2014)

AC electrospray is used for mass spectrometry applications. The microjet from AC spray, unlike DC spary, does not develop a plume that loses much of the analyte. Hence, AC spray can be used without a sheath flow. AC sprayed droplets are weakly charged and hence can achieve soft ionization. AC spray can also preferentially entrain low-mobility anions and offer a means of controlling the pH in the spray by tuning the frequency. Since the charge state of proteins is a function of pH, this offers a means of producing large and distinct charge/mass signals.

US Patent US8771938 (2014), CA2702276C and licensed to F Cubed, LLC, now CubedLaboratories

Molecular hybridization onto probe-functionalized nanostructures sensitively affects their polarizability and dielectrophoretic mobility, allowing rapid detection of hybridization events and multi-plex diagnostics on biochips. The large polarizability and induced field of carbon nanotubes is used to assemble them across electrodes and to rapidly trap analyte molecules from a flowing solution

US Patents US8635028 (2011); US10273522 (2019); Canadian patents CA2702276C and licensed to ImpeDx

A rapid dielectrophoresis and impedance method for detecting bacteria viability by concentrating and sensing bubbles generated by the antibiotically screened bacteria.

US Patent US8267914 (2012)

A new high-frequency AC Electrospraying, droplet generation and electrospinng technology. The AC cone exihibits an 11 degree angle different from the 49 degrees DC Taylor cone and produces small electro-neutral drops. AC frequency minimizes field and current penetration and hence enhances molecular and cell viability. AC electrospinning provides mechanically strong multi-fiber threads at high throughput without the whipping instability of DC electrospinning, thus allowing high-throughput production.

US Patent US7960180 (2011) and licensed to Scientific Methods Inc.

Silica beads with different functionalized surface groups can trap and release virus in different buffers due to proper tuning of double-layer effects. The technology can be used to clean water or concentrate pathogens for detection.

US Patent US7744738 (2010)

A serpentine wire design allows high-field dielectrophoretic trapping and manipulation of cells, molecules and other bioparticles. The field is significantly higher than that possible for disjoint electrode pairs to achieve much higher capture efficiency.

Taiwan patent TW1322032B (2008)

Mini and microvortices around a perm-selective granule or perm-selective membrane is used to achieve rapid mixing at micron to mm scales. Free-floating granules are propelled by asymmetry of the vortices due to asymmetric concentration polarization in the field direction. This ballistic motion allows the granule to achieve global mixing in a large reservoir.

United States Letters Patent US6428754 (2002).

A by-pass design reduces the heat load into a catalytic converter such that ignition occurs at the leading edge of the converter and the heat of reaction can be profitably used to lightoff the entire converter. With the bypass, the converter lights off in less than a minute compared to the10 minute light-off without the bypass.

US Patent US5311932 (1994)

Sequential twisting of a heating coil in two different planes enhances heat transfer by chaotic mixing action of inertial Dean vortices.