University of California

Daniel R Gossett

Dino Di Carlo

Henry T K Tse

Aram J Chung

Westbrook Weaver

Henry TK Tse

A system for deforming and analyzing a plurality of particles carried in a sample volume includes a substrate defining an inlet, configured to receive the sample volume, and an outlet; and a fluidic pathway fluidly coupled to the inlet and the outlet. The fluidic pathway includes a delivery region configured to receive the plurality of particles from the inlet and focus the plurality of particles from a random distribution to a focused state, a deformation region defining an intersection located downstream of the delivery region and coupled to the outlet, and wherein the deformation region is configured to receive the plurality of particles from the delivery region and to transmit each particle in the plurality of particles into the intersection from a single direction, a first branch fluidly coupled to the deformation region and configured to transmit a first flow into the intersection, and a second branch fluidly coupled to the deformation region and configured to transmit a second flow, substantially opposing the first flow, into the intersection, wherein the first flow and the second flow are configured to induce extension of one or more particles in the plurality of particles.

System and method for deforming and analyzing particles

A system is disclosed that enables the automated measurement of cellular mechanical parameters at high throughputs. The microfluidic device uses intersecting flows to create an extensional flow region where the cells undergo controlled stretching. Cells are focused into streamlines prior to entering the extensional flow region. In the extensional region, each cell's deformation is measured with an imaging device. Automated image analysis extracts a range of independent biomechanical parameters from the images. These may include cell size, deformability, and circularity. The single cell data that is obtained may then be used to in a variety of ways. Scatter density plots of deformability and circularity may be developed and displayed for the user. Mechanical parameters such as deformability and circularity may be gated or thresholded to identify certain cells of interest or sub-populations of interest. Similarly, the mechanical data obtained using the device may be used as cell signatures.

Method and device for high throughput cell deformability measurements

A method of exchanging fluids with suspended particles includes providing a microfluidic device with a first inlet channel operatively coupled to a source of particles and a second inlet channel operatively coupled to an exchange fluid. A transfer channel is connected at a proximal end to the first inlet channel and the second inlet channel. First and second outlet channels are connected to a distal end of the transfer channel. The source of particles is flowed at a first flow rate into the first inlet channel while the exchange fluid is flowed at a second flow rate into the second inlet channel wherein the ratio of the second flow rate to the first flow rate is at least 1.5. Particles are collected in one of the first and second outlet channels while fluid substantially free of particles is collected in the other of the first and second outlet channels.

Method and device for high-throughput solution exchange for cell and particle suspensions

A system for deforming and analyzing particles includes a substrate defining an inlet, and an outlet; a fluidic pathway fluidly coupled to the inlet and the outlet and defining a delivery region upstream of a deformation region configured to deform particles, wherein the fluidic pathway comprises a first branch configured to generate a first flow, and a second branch configured to generate a second flow that opposes the first flow, wherein an intersection of the first flow and the second flow defines the deformation region; a detection module including a sensor configured to generate a morphology dataset characterizing deformation of the particles, and a photodetector configured to generate a fluorescence dataset characterizing fluorescence of the particles; and a processor configured to output an analysis of the plurality of particles based at least in part on the deformation dataset and the fluorescent dataset for the plurality of particles.

System for deforming and analyzing particles

Method and device for high-throughput solution exchange for cell and particle suspension

System and method for deforming, imaging and analyzing particles

A method of monitoring temporal and spatial information of cells includes trapping a plurality of cells within single cell traps contained in a microfluidic device having an inlet, and an outlet. A first fluorescent stain specific to a first target is flowed into the inlet of the device and exposed to the trapped cells. The trapped cells are then imaged as a function of time. A fluorescent stain specific to a different target is flowed into the inlet of the device, the subsequent fluorescent stain having an emission spectrum that substantially overlaps with the emission spectrum of the prior fluorescent stain. The plurality of trapped cells are then imaged again as a function of time. The process can be repeated with additional fluorescent stains having substantially overlapping emission spectra. Images may be subtracted to reveal the contribution of a single fluorescent stain.

Growing community of inventors

Los Angeles, CA, United States of America

Daniel R Gossett