Microhole Chip Rapidly Identifies Tumor Cells

The higher the concentration of tumor cells in the bloodstream, the greater the risk of metastasis. The number of circulating tumor cells indicates how well a patient is responding to therapy.

A new microhole chip has been developed that enables cells to be identified and characterized reliably within minutes. The conventional method of fluorescence-activated cell sorting (FACS analysis) provides only a rough estimate of the number of tumor cells circulating in the blood.

Scientists at the Fraunhofer Institute for Biomedical Engineering (IBMT, Sulzbach, Germany) recently completed a collaborative project concerning the identification of circulating tumor cells; a two-step cell analysis method was applied. In the first step, suspicious-looking cells were selected using a microscope. In the second step, the selected cells underwent detailed analysis using the more time-intensive method of Raman spectroscopy. This involves exposing the cells to light in a defined frequency range. Tumor cells scatter light in a specific way that allows them to be clearly identified. Raman spectroscopy cannot be used on conventional arrays with a glass or polymer substrate, because these materials interfere with the measurement, but this is no problem for the new IBMT chip and its silicon-nitride substrate.

Another advantage of the new microhole chip is that it can be populated with 200,000 cells, each one in a separate hole, in a matter of minutes. A micropipette is used to remove individual tumor cells from the chip for further analysis. The level of underpressure chosen to hold them in place is too low to cause any damage. Molecular-biology analysis is a useful means of identifying the factors that determine why a specific drug is able to kill tumor cells or has no effect. The new microhole chip has many other possible applications: as a selection system for protein-producing cells, for instance, such as those required to make insulin and other biopharmaceuticals.

Thomas Velten, PhD, whose team developed the microhole chip, said, “Our new microhole chip allows single cells to be picked out of the blood sample, placed on separate holes in the substrate for analysis, and removed individually afterwards. It's easy to select cells because each one has its own specific position in the array, where they are lined up like ducks in a row. Each cell is placed on a hole but cannot slip through it. A slight underpressure is applied to the cells that hold each one in its allotted place by suction.”

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Fraunhofer Institute for Biomedical Engineering