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Molded microfluidic device makes gel “apartments” for single cells

Hydrogel device allows localized treatment and analysis of 10,000 individual cells at a time

by Fernando Gomollón-Bel, special to C&EN
February 25, 2020

Gloved hand holding a clear microfluidics chip with orange compartments and channels printed on it.
Credit: Anal. Chem.
This microfluidic device contains 10,000 cell apartments in just over 2 cm2.

A new microfluidic device that traps individual cells in microscopic hydrogel “apartments” allows the cells to be individually treated and analyzed much more readily than with previous devices (Anal. Chem. 2020, DOI: 10.1021/acs.analchem.9b05099).

Benjamin B. Yellen, a materials scientist at Duke University who led the study, says the device could find a myriad of applications, whether testing individual cells’ response to drugs or performing genetic analysis in drug-resistant cells, he says.

To create the array of tiny cell apartments, Yellen and his colleagues first placed a polydimethylsiloxane (PDMS) mold outlining 10,000 interconnected, crescent-shaped compartments, each about 0.5 mm across, on top of a silicon chip. They then injected a stream of cells that became trapped individually in each of the compartments. To fix the cells in the array, the researchers flowed a solution of biocompatible hydrogel through the mold, let it cure around the cells, and then peeled off the mold. The device is open on the top, allowing access to the cells for genomic modifications or for printing biochemical reagents such as fluorescent dyes onto individual apartments, says study coauthor Ying Li, a biochemist at the Chinese Academy of Sciences’s Wuhan Institute of Physics and Mathematics.

Micrograph shows several rows of crescent shaped cellular compartments with a large opening on one side and a small hole on the other to trap cells.
Credit: Anal. Chem.
Scanning electron microscope image of the microfluidic device showing the microscopic cell apartments labelled with a street and an apartment number for identification.

The method was able to trap single human cells in 80% of the apartments on the chip. Each dwelling can be easily identified through a microscope thanks to street and apartment numbers embossed in the polymer mold, corresponding to row and column.

The researchers demonstrated the advantages of the device’s top access by delivering a labeled DNA sequence to cells in the array and showing they could selectively illuminate cells carrying a certain gene. The team also amplified the genomes of individual cells in parallel to show that the cells’ genes could be analyzed efficiently, Li says. This technique could allow researchers to identify drug-resistant cells from patient biopsy samples, for example, and then identify differences in the cells’ gene sequences relative to the patient’s healthy cells.

Katherine Elvira, an expert in microfluidics at the University of Victoria who was not involved in the study, loves the idea of using PDMS as a mold for curing the hydrogel, and that the lid can then be peeled off. Unlike other methods, this allows direct access to cells once they are loaded into a device, but this new technique “means we can analyze each individual cell to see what makes it different,” she says. “This will give us a better understanding of diseases, aging, drug response, and much more.”



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