New technology to analyze and sample single cells without using labeling material
In the framework of JST’s program “Development of Advanced Measurement and Analysis Systems”, Sony Corporation and Tokyo Medical and Dental University have developed the world first technology enabling discrimination of single cells without labeling material by using the difference of their electric properties.
Recently, analysis and sampling of single cells have become more important for studies of regenerative medicine or cell transformations induced by diseases, for example. To bring regenerative medicine into clinical practice, precise sorting of stem cells from other cells is critical. Also, to understand the mechanisms of diseases like cancer, pathological change of normal cells must be thoroughly traced. The instruments commonly used for analysis of single cells are flow cytometers, which Sony, among other manufacturers, is developing and selling. Flow cytometers enable fast, accurate analysis of cells, color-coded with labeling material such as fluorescent dyes, and sampling of only targeted ones. There is another demand, however, for analysis and sampling of a certain number of cell types, for which no color-coding reagent is available. Thus, recently, a few instruments that discriminate single cells through analysis of their electric impedances (*1) have been developed. With conventional technologies, however, impedances at only two frequencies can be analyzed, and the information obtainable from them is limited to the size and density of a cell.
Sony original technology enables simultaneous analysis of impedances at 16 frequencies for single cells passing through the detector in one millisecond. In addition, by optimizing the fluidic structure and electrode configuration of the microfluidic chip (*2), in which cells flow, measurement noises have been drastically reduced. With these realized, the information on the difference or change of the electric properties of the membrane and interior of a cell is obtainable through analysis of the dielectric spectrum (*3) calculated from the frequency dependent impedance for each cell.
In collaboration with Professor Shuki Mizutani’s group at Tokyo Medical and Dental University, we succeeded in discriminating two types of cancer cell lines solely on the basis of the difference in dielectric spectrum.
Furthermore, for sorting and sampling of cells after they are analyzed, the technology to control the flow direction of cells by applying an electric field upon the fluidic channel has been developed. This has been achieved by flow simulations and optimizations of electrode structure and other parameters in the fluidic channel. The simulations were used to precisely predict the motion of cells flowing in the electric field, according to a technology developed in collaboration with Professor Kazuyoshi Nakabe’s group at Kyoto University.
In the future, on the basis of these achievements, it is expected that a variety of cells analyzed, sorted, and sampled without using labeling material can be practically used asneeded in life science researches such as regenerative medicine, immunology, and so on.
These achievements are presented at the international conference “μTAS 2011” in Seattle, USA from October 2nd (PDT), 2011. Also, a prototype of the instrument is exhibited at “Bio Japan 2011” in Pacifico Yokohama from October 5th (Japan Time).