University of Notre Dame Du Lac

Other

University of Missouri

Gas Research Institute

Scientific Methods, Inc.

Hsueh-Chia Chang

Satyajyoti Senapati

Zdenek Slouka

David B Go

Zachary Gagnon

Sagnik Basuray

Shramik Sengupta

Sachidevi Puttaswamy

Sunny S Shah

Zehao Pan

Mihir Sen

Gilad Yossifon

David T Leighton

Fu-Chih Hsu

David A Battigelli

Siddharth Maheshwari

Zilin Chen

Donny Hanjaya-Putra

Steven Marczak

Shoupeng Liu

Vivek Yadav

Yunshan Wang

Zeinab Ramshani

Yu Yan

Peter Mushenheim

Reginald Hill

Jason Gordon

Satyajyoti Senpati

Diya Li

Nishant Chetwani

Ceming Wang

Steve Marczak

Catherine Cassou

Loan Bui

Li-Jing Cheng

Shau-Chun (Paul) Wang

Yongfan Men

Dmitri Lastochkin

Leslie Yeo

Described herein is a method for encapsulating single cells using alternating current electrospray technology in tip streaming mode. The encapsulation efficiency is over 80% and natural (alginate, collagen) and synthetic (NorHA) hydrogels and various cell types can be used. The encapsulated cells can be implanted and are protected from the host's immune response. In addition, the coating allows better tissue growth in laboratory cell cultures with a conformal mechanical support that allows molecular and nutrient transport.

Method of encapsulating single cells utilizing an alternating current electrospray

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.

AC electrosprayed droplets for digital and emulsion PCR

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.

Systems and methods for separating, detecting, and quantifying a target polynucleotide

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.

Integrated membrane sensor for rapid molecular detection

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&#xd7;PBS buffer, cell culture media and blood serum. Using flow rates from 150 &#x3bc;L/hr to 200 &#x3bc;L/hr and field strengths of 100 V/cm, we consistently captured between 60% to 80% of exosomes from buffer, cell culture media, and blood serum as confirmed by both fluorescence spectroscopy and nanoparticle tracking analysis. Our microfluidic chip maintained this recovery rate for more than twenty minutes with a concentration factor of 15 for ten minutes of isolation.

Simultaneous isolation and preconcentration of exosomes by ion concentration polarization method and apparatus

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.

Methods and apparatus for a shear-enhanced CNT-assembly nanosensor platform for ultra-sensitive and selective protein detection

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

Ultra-sensitive multi-target lateral flow molecular assay with field-induced precipitation

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.

Methods and apparatus for nanomembrane-based nucleic acid sensing platform for portable diagnostics

An improved system and method is provided for detecting viable bacteria in a suspension sample. A sample of a suspension in which bacterial presence is suspected is collected from a source and a portion of the sample transferred to a microfluidic unit. A series of analysis signals at different frequencies are applied to the sample portion. An impedance is measured via a signal analyzer for the sample portion for each of the analysis signals to define an impedance data set. An initial bulk capacitance value is determined for a model circuit based on the impedance dataset. After a predetermined time period, a new bulk capacitance value is determined for on another portion of the sample. The difference between the new bulk capacitance and the initial bulk capacitance value is compared to a threshold value to determine if viable bacterial is present in the sample.

Rapid detection of viable bacteria system and method

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.

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.

Method and apparatus for a nanopipette biosensor

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.

Microchamber electrochemical cell having a nanoslot

Disclosed are example methods and devices for detecting one or more targets. An example method includes placing a sample including a first target with in a microfluidic device and hybridizing a plurality of copies of the first target with a plurality of nanostructures. The example method includes applying an electric current to the plurality of nanostructures and using an electric field created by the electric current to move the plurality of nanostructures. In addition, the plurality of nanostructures are sorted and evaluated to determine at least one of a presence, an absence, or a quantity of the first target.

Microfluidic platforms for multi-target detection

An alternating current electrospray mass spectrometry device includes an electrospray device having at least one emitter providing a passageway for transmission of an analyte sample. At least one conductive element is in electrical communication with the at least one emitter. A power source generates an alternating current electric field to form a liquid cone at a tip of the emitter and ionizes the analyte sample present in the liquid cone. The frequency of the electric field entrains low mobility ions in the liquid cone. The AC electric field causes the emitter to discharge the liquid cone as a liquid aerosol drop, and a mass spectrometry device analyzes the ionized analyte sample to determine the composition of the contained analyte sample.

Methods and apparatus for mass spectrometry utilizing an AC electrospray device

Growing community of inventors

Granger, IN, United States of America

Hsueh-Chia Chang