Nanotech News

October 24, 2005

Lab-on-a-Chip Device Isolates Rare Cancer Cells in Minutes

Imagine the day when a physician can take a drop of a patient’s blood and within minutes identify the presence of circulating malignant cells. That day is now closer as a result of work published by investigators at Redmond, WA-based microfluidics company Micronics, which has created a credit card sized lab-on-a-chip device that can isolate rare cancer cells, count them, and purify the nucleic acids in those cells, all within a matter of minutes. Back-to-back papers in the journal Methods highlight the development of this device and provide proof-of-concept data.

With small business funding from the National Cancer Institute’s Innovative Molecular Analysis Technology program, a team led by C. Fred Battrell, Ph.D., developed a device that can sort rare cancer cells from a thin ribbon of cells lined up within a microfluidics channel. Viewing multiple cells simultaneously increases the speed at which the device can process cells, and enables the device to rapidly concentrate rare cancer cells from blood.

The device was designed to rapidly mix cells with antibodies that recognize proteins on the surface of cancer cells. The antibodies contain a fluorescent probe that enables a miniaturized fluorescence detector built into the device to identify the cancer cells labeled by these antibodies. As a result of the device’s design, the investigators estimate that it can accurately signal the presence of 1,000 and 10,000 times fewer cancer cells hiding in a blood sample than flow cytometry, the current state-of-the-art technology used to isolate and count specific cells from biological samples.

In the second Methods paper, the Micronics team reported on its development of a second set of microfluidics circuits that can identify RNA that is diagnostic of cancer. These circuits start with cancer cells that have been separated from a blood sample. These cells first pass through a cell-disrupter, built into the chip, that releases a cell’s nucleic acids into the microfluidics channel. A silica membrane integrated into the device captures the freed nucleic acids, which has the end effect of separating the nucleic acids from other cellular components such as proteins and salts.

Once purified, a storage chamber on the chip releases a buffer that causes the membrane to release the nucleic acids. They then pass into another microfluidics chamber, where polymerase chain reaction (PCR) takes place. PCR amplifies the nucleic acid for subsequent identification. As a proof-of-principle, the investigators assayed cells using this procedure for RNA associated with a gene mutation tied to chronic myelogenous leukemia (CML). The next step is to integrate these two operations – cancer cell isolation and PCR identification – onto one chip.

The cell-separation work is detailed in a paper titled, “Rare cancer cell analyzer for whole blood applications: Microcytometer cell counting and sorting subcircuits.” An abstract is available through PubMed.
View abstract.

The nucleic acid separation and identification work is detailed in a paper titled, “Rare cancer cell analyzer for whole blood applications: Automated nucleic acid purification in a microfluidic disposable card.” An abstract is available through PubMed.
View abstract.