Microfluidic chip for analysis of single cells

August 17, 2018, Wiley
Microfluidic chip for analysis of single cells
Credit: Wiley

A few little cells that are different from the rest can have a big effect. For example, individual cancer cells may be resistant to a specific chemotherapy—causing a relapse in a patient who would otherwise be cured. In the journal Angewandte Chemie, scientists have now introduced a microfluidics-based chip for the manipulation and subsequent nucleic-acid analysis of individual cells. The technique uses local electric fields to highly efficiently "trap" the cells (dielectrophoresis).

Molecular analyses of individual are necessary to better understand the role of heterogenous cell populations in the development of diseases and to develop effective therapies for personalized medicine. Identifying in a mass of other cells is an enormous challenge in diagnostic medicine. The cells must be sorted, held, transferred into another container with an extremely small volume (< 1 μL) and then must undergo molecular analysis. Conventional methods are usually very time consuming and complex, as well as unreliable and inefficient. They can also compromise the viability of the cells, require large sample volumes, have a high risk of contamination, and/or require expensive instruments.

Scientists from the University of Washington (Seattle, USA), Iowa State University (Ames, USA), and Fred Hutchinson Cancer Research Center (Seattle, USA) have used microfluidic technology to overcome these problems. All of the necessary steps occur reliably on a specially developed microchip using minimal amounts of solvent and without requiring the cells to be marked. In contrast to conventional microfluidic chips, this one requires neither complex fabrication technology nor components like valves or agitators.

The Self-Digitization Dielectrophoretic (SD-DEP) chip is about the size of a coin and has two parallel microchannels (50 μm deep x 35 μm wide x 3.2 cm long) connected by numerous tiny little chambers. The openings of the microchannels are only 15 μm wide. A thin electrode is stretched along the length of the channels. The channels and chambers are filled with a buffer, an alternating voltage is applied, and the sample is added to one of the microchannels. The team headed by Robbyn K. Anand and Daniel T. Chiu used in their experiments.

Local maxima of the electric field occur at the narrow entrances to the chambers. Cells that enter the chambers are "trapped". Because the dimensions of the entrance are similar to the average size of a cell, only a single cell can be trapped by each entrance. When the alternating current is switched off and the flow rate is increased by injection of the reagents required for subsequent analysis, the cells are washed into the chambers. An oil is then added to seal the chambers. The cells are then dissolved, and the nucleic acids are released and multiplied and can be identified as leukemia cells by a marker gene.

In future studies, the researchers hope to use the chip to determine the distribution of genetic mutations that are related to resistance in leukemia cells and thus may cause relapses.

Explore further: Next-generation drug testing on chips

More information: Yuling Qin et al, A Self-Digitization Dielectrophoretic (SD-DEP) Chip for High-Efficiency Single-Cell Capture, On-Demand Compartmentalization, and Downstream Nucleic Acid Analysis, Angewandte Chemie International Edition (2018). DOI: 10.1002/anie.201807314

Related Stories

Next-generation drug testing on chips

August 25, 2017

Researchers at Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) in Japan have designed a small 'body-on-a-chip' device that can test the side effects of drugs s on human cells. The device solves ...

Recommended for you

Targeting 'hidden pocket' for treatment of stroke and seizure

January 19, 2019

The ideal drug is one that only affects the exact cells and neurons it is designed to treat, without unwanted side effects. This concept is especially important when treating the delicate and complex human brain. Now, scientists ...

Artificially produced cells communicate with each other

January 18, 2019

Friedrich Simmel and Aurore Dupin, researchers at the Technical University of Munich (TUM), have for the first time created artificial cell assemblies that can communicate with each other. The cells, separated by fatty membranes, ...

Using bacteria to create a water filter that kills bacteria

January 18, 2019

More than one in 10 people in the world lack basic drinking water access, and by 2025, half of the world's population will be living in water-stressed areas, which is why access to clean water is one of the National Academy ...

Hand-knitted molecules

January 18, 2019

Molecules are usually formed in reaction vessels or laboratory flasks. An Empa research team has now succeeded in producing molecules between two microscopically small, movable gold tips – in a sense as a "hand-knitted" ...

This computer program makes pharma patents airtight

January 17, 2019

Routes to making life-saving medications and other pharmaceutical compounds are among the most carefully protected trade secrets in global industry. Building on recent work programming computers to identify synthetic pathways ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.