Massachusetts Institute of Technology

Nanyang Technological University

The General Hospital Corporation

National University of Singapore

The Broad Institute, Inc.

Massachusetts General Hospital Corporation

Han Wei Hou

Jongyoon Han

Say Chye Joachim Loo

Chwee Teck Lim

Roby Bhattacharyya

Krystyn J Van Vliet

Galit Alter

Ali Asgar Bhagat

Wong Cheng Lee

Hui Min Tay

Aniruddh Sarkar

Deb Hung

Nishanth Venugopal Menon

Bernhard Otto Boehm

King Ho Holden Li

Soon Nan Wee

The present disclosure provides a device for patterning extracellular matrix (ECM) hydrogel comprising a first layer surface patterned to define a microchannel, a second layer comprising a loading channel in fluid communication with loading ports to receive an ECM hydrogel, wherein the first layer is attached over the second layer such that the patterned surface faces the loading channel to define an open chamber with regions of reduced cross-sectional area, and wherein the ECM hydrogel is confined to fill said regions, thereby forming a perfusable channel in the open chamber. The present disclosure also provides the same device wherein the second layer is a substrate without a loading channel and is optically pervious; and additionally provides a method of patterning ECM hydrogel comprising use of the aforementioned device. Importantly, ECM patterning is achieved by surface tension between the ECM hydrogel and the first layer at the boundaries of the microchannel.

Three-dimensional (3D) hydrogel patterning in microfluidic vascular models

This invention relates to a method for separating blood cells comprising the steps of: (a) lysing red blood cells of a blood sample and diluting said sample; (b) providing a microfluidic device comprising a spiral-shaped flow channel having at least a first end and a second end, wherein said flow channel has two inlet ports at or near said first end and at least two outlet ports at or near said second end, wherein one of the two inlet ports is located at the inner wall of the spiral-shaped flow channel and the other inlet port is located at the outer wall of the spiral-shaped flow channel and at least one of the outlet ports is connected to a container allowing the storage of blood cells; (c) introducing the sample of step (a) into the inlet port located at the outer wall of the spiral-shaped flow channel and introducing a sheath fluid into the inlet port located at the inner wall of the spiral-shaped flow channel; (d) driving said sample and the sheath fluid through the spiral-shaped flow channel; and (e) recovering the blood cell in the at least one container connected to the at least one outlet port. The present invention also relates to coupling above described method of purifying neutrophils in the native state with a method for diagnosing diabetes or an inflammatory disease in a subject, which involves further investigation of neutrophils by determining their rolling speed, the neutrophil circularity (NC) index and/or the expression of markers, such as intracellular reactive oxygen species (ROS), CD1 1 b or PSGL-1.

Leukocyte and microparticles fractionation using microfluidics

In accordance with an embodiment of the invention, there is provided a method for: a) high-throughput, multiplexed, affinity-based separation of proteins&#x2014;especially low abundance proteins&#x2014;from complex biological mixtures such as serum; and b) high-throughput, multiplexed, affinity-based separation of cells&#x2014;especially rare cells&#x2014;from complex biological mixtures such as blood or blood fractions. The separation of proteins or cells is achieved based on differential binding to affinity-capture beads of different sizes and then sorting the protein-bound or cell-bound beads using the concept of centrifugal-induced Dean migration in a spiral microfluidic device. This method enables continuous-flow, high throughput affinity-separation of milligram-scale protein samples or millions of cells in minutes after binding. This is particularly applicable to the isolation of antigen-specific antibodies from polyclonal sera and antigen-specific immune cells or circulating tumor cells from blood, both of which are otherwise highly labor-intensive and expensive to perform.

System and method for multiplexed affinity purification of proteins and cells

A method and microfluidic device useful for isolating microbes from a blood sample which includes introducing the blood sample into the sample inlet of a spiral microfluidic device; and introducing a second fluid into the sheath inlet of the microfluidic device, wherein the spiral channel terminates in a microbe outlet and a waste outlet, and wherein the spiral channel includes a length, height, and a width that define an aspect ratio adapted to isolate any microbes present in the sample along a first portion of the spiral channel terminating at the microbe outlet, and to isolate red blood cells and leukocytes along a second portion of the spiral channel terminating at the waste outlet; and collecting the microbes from the microbe outlet, thereby isolating the microbes.

Microfluidic microbe detection and isolation

A method of detecting one or more diseased blood cells in a blood sample includes introducing a blood sample into at least one inlet of a microfluidic device comprising one or more linear channels wherein each channel has a length and a cross-section of a height and a width defining an aspect ratio adapted to isolate diseased blood cells along at least one portion of the cross-section of the channel based on reduced deformability of diseased blood cells as compared to non-diseased blood cells, wherein diseased blood cells flow along a first portion of the channel to a first outlet and non-diseased blood cells flow along a second portion of the channel to a second outlet. The one or more channels can be adapted to isolate cells along portions of the cross-section of the channel based on cell size. In some embodiments, the one or more channels can be spiral channels.

Microfluidics sorter for cell detection and isolation

Growing community of inventors

Singapore, Singapore

Han Wei Hou