Abstract:
Bioassays are provided for detecting and analyzing responses from single cells and cell pairs suspended in micro-scale droplets (80-200 μm 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.
Abstract:
Microfluidic devices and methods are provided for high-throughput generation, culturing, and analysis of cell spheroids, with subsequent isolation of selected cell spheroids for further analysis or isolation and expansion of cells from the spheroids. Any desired types of cells and matrices can be combined to form the cell spheroids and used to screen drugs and immunotherapy agents or methods, including in a personalized medicine format. Cell spheroids also can be cultivated and analyzed under hypoxic conditions. A particular advantage of the technology is the ability to isolate, enrich, and/or expand cells identified as having, or induced to have, desirable properties, such as immune cells that can be produced ex vivo and returned to the patient to combat a tumor or pathogen in vivo.
Abstract:
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.
Abstract:
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.
Abstract:
A platform technology for the detection and quantification of biomarkers in exosomes secreted by single cells uses a microfluidic system and provides methods of diagnosis and prognosis of cancer and other conditions using the biomarkers. Single cells can be obtained from a subject and characterized by their exosome population. The biomarkers can be detected at extremely low levels using rolling circle amplification and multiplex analysis to enhance specificity and sensitivity of the analysis.
Abstract:
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.
Abstract:
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.
Abstract:
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.
Abstract:
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.
Abstract:
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.