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Single-Cell Analysis: Quick and Easy Detection

  R&D DIGEST  

Assistant professor Chang Lu and graduate student Hsiang-Yu Wang use a low-power laser to look at a microchip through a microscope. The microfluidic device rapidly analyzes single cells for early disease detection.

Researchers at Purdue University (West Lafayette, IN) have designed a microfluidic device that quickly analyzes cells one at a time. Using a process called electroporation, the device produces an electrical current so that materials inside a cell can be examined for abnormalities. This is critical for detecting diseases at a very early stage.

Electroporation opens pores in a cell's outer membrane to allow outside materials to move through the cell. Electrical pulses control the period of time that cells are exposed to the electric field. If the cells are exposed for too long, they die. Purdue researchers are using a common dc power supply, rather than the pulse generator often used in electroporation experiments. The generator can be expensive and complex. Using the dc power supply makes the device “dramatically simple,” says Chang Lu, PhD, assistant professor of agricultural and biological engineering at Purdue.

Researchers are focusing on two areas. The first application of the microfluidic device is drug and gene delivery. For example, molecules might not be able to get into the cell membrane because of their size. By using electroporation, the electrical field creates a pulse that allows the delivery of drugs or genes into the cells.

The device's second use is for the chemical analysis of single cells. When the electric field strength is very high, around 1000 V/cm, the cell membrane ruptures. Researchers can then analyze the intracellular materials as they exit single cells. Such rapid analysis of single cells could provide faster and more-precise detection of a disease earlier than usual. For example, at a disease's early stage, an indicative biomarker or protein may only be present in one or a few cells. “If you run the test based on the entire population, you won't be able to see them, because the number is too small—they'll be buried in the average signal,” explains Lu. “If you're running a single-cell analysis and looking at the cells one by one, there's a chance you can catch the presence of a disease.” The faster the device can analyze a cell, the better, says Lu. His current expectation of its analysis rate is about 50–60 cells per minute.

One of the biggest advantages of the device is its small and simple footprint. The only microfluidic component is the channel, which measures about 3–5 mm long and 200 µm wide. Variations in width determine how long the cells are exposed to the electroporation field. “Because of the physical dimensions of the microfluidic channel, we can easily control its dimension so only one cell goes through the narrow section at a time,” says Lu. “That gives us the advantage of dealing with a really small amount of cells.”

The other component is the dc power supply, which establishes the electrical field across the channel. A syringe pump controls the flow rates of the cells inside the channel.

The simplicity of the device could be a plus when it comes to commercialization. It can also be integrated so that multiple devices run on the same chip. This gives the device high throughput, because it is able to run the same processes in parallel. Before commercialization, however, the researchers need to find a better way to control the flow rate of cells and prevent the clogging of cells, which could mean coating the microfluidic channel walls.

More information about the new device and the research team's study can be found in Analytical Chemistry, which is published by the American Chemical Society. The Purdue Research Foundation has filed a patent on the device.

Copyright ©2006 Medical Device & Diagnostic Industry
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