Northeastern University

The General Hospital Corporation

Tania Konry

Saheli Sarkar

Pooja Sabhachandani

Martin L Yarmush

Noa Cohen

Giovanni Ugolini

Ji Won Lim

Wenjing Kang

A high throughput microdroplet-based system for single cell assays in microdroplets is provided. The system integrates parallel devices and switches to enable simultaneous analysis of different cells or cell combinations, or different assay conditions, on a single microfluidic chip. Interconnections between the inlets of individual devices on a common chip enable simultaneous screening of the effect of different combinations of drugs on single cells. The use of an oil inlet and microchannels with matched total flow resistance allows the synchronous generation of droplets with the same dimensions and/or volumes.

Parallel microfluidic device for high throughput cell assays in microdroplets

The technology provides arrays of microwells with reversible shape for culture, analysis, and recovery of individual cells or groups of cells. The microwells are reversibly formed by vacuum-induced deflection of an elastomeric membrane into an array of microwell molds formed in a microwell substrate. The shape of each microwell or groups of microwells can be selectively altered by applying or releasing vacuum to individual microwells. The devices, systems, and methods utilizing the technology enable collection of individual cells for further study or therapeutic use without the need for micromanipulation.

Single cell isolation and processing system with reversible well shape

Microfluidic devices for use with reagents bound to microspheres for determination of the concentration of an analyte in a liquid sample are provided. The devices include two sequential mixing channels that promote rapid binding of microsphere-bound reagents with reagents in solution and a means for detecting labeled microsphere-bound reaction products. Also provided are methods for using the devices with microsphere-bound reagents to determine the concentration of an analyte in a liquid sample and to measure the binding affinity of antibody for an antigen.

Microfluidic system and method for real-time measurement of antibody-antigen binding and analyte detection

The invention provides a device, method, and system for high throughput detection of nucleic acid expression in individual cells. Cells are encapsulated in aqueous microdroplets which are merged with a biocompatible matrix, allowing on-chip fluorescence in situ hybridization on both adherent and non-adherent cells. The invention also provides multiplexed detection of nucleic acids, proteins, and cellular activity. The device and methods can be used to assess cellular interactions and to test the effects of antitumor agents.

Single cell fluorescence in situ hybridization in microfluidic droplets

Bioassays are provided for detecting and analyzing responses from single cells and cell pairs suspended in micro-scale droplets (80-200 &#x3bc;m diameter) generated in microfluidic devices. Cell responses to various stimuli are analyzed. The stimuli are delivered by homotypic or heterotypic cells, small molecule drugs, and therapeutic agents including immunotherapeutics. The bioassays can be used to describe heterogeneity in any given cell population, and can be used in a clinical setting, such as profiling of patient-derived cells, designing personalized treatment strategies, and optimizing drug combinations for immunotherapy of tumors.

Live single-cell bioassay in microdroplets

Methods, devices, and kits for performing rapid, highly sensitive, high throughput, accurate, and flexible detection and quantification of nucleic acids based on highly optimized rolling circle amplification are provided. The methods, devices, and kits can be used to detect and track an emergent virus or other pathogen, including SARS-CoV-2, to test and diagnose individual patients with respect to a specific pathogen or disease, including COVID-19, and to detect and analyze cellular nucleic acids. The methods and devices also can be used to detect fragments and variants of DNA or RNA, including those present in cancer cells. The methods, devices, and kits are suitable for use in both high throughput screening carried out in centralized testing laboratories and in point-of-care testing devices used in the field, at home, in the workplace, or at public facilities for rapid detection and diagnosis.

Colorimetric and multiplexed isothermal RNA-based assay for SARS-CoV-2 and other viral diagnostics and cell analysis

A microfluidic device provides high throughput generation and analysis of defined three-dimensional cell spheroids with controlled geometry, size, and cell composition. The cell spheroids of the invention mimic tumor microenvironments, including pathophysiological gradients, cell composition, and heterogeneity of the tumor mass mimicking the resistance to drug penetration providing more realistic drug response. The device is used to test the effects of antitumor agents.

Microfluidic device and method for analysis of tumor cell microenvironments

Platform technology involving aqueous microdroplet reaction vessels created, arrayed, and characterized by imaging microscopy in a microfluidic device are applied to a wide variety of bioassays involving the detection and phenotypic characterization of single cells. The bioassays include the rapid and automated detection of microbial pathogens and their antibiotic sensitivity from patient samples as well as the characterization of immune responses using a patient's own cells, including the killing of tumor cells.

Growing community of inventors

Boston, MA, United States of America

Tania Konry