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Microfluidics Assisted Cell Screening



Technology:
New platform for cell-based, high throughput screening

Markets Addressed


Cell-based screening is used in biological research and drug discovery, trying to identify substances (e.g. small molecules, peptides, RNAi) that induce a particular phenotypic change within a cell. Typically such phenotypic changes are monitored through the use of fluorescent indicators and/or changes in cell morphology.

To enable substances to be screened in a high-throughput manner, current screening technologies rely on one either automated digital fluorescent microscopy and/or flow cytometry. Both of these methods have their pros and cons: Microscopy is highly sensitive – allowing detection of single fluorescent molecules – and provides superior information in terms of cell morphology and size, as well as protein localization and abundance. In contrast, flow cytometry enables much higher throughput screening, with analysis and sorting of >500,000 cells per minute. An ideal screening technology would therefore combine the best features of both these methods.

As a new platform for cell-based, high-throughput screening (HTS) it can be used in the pharmaceutical and biotechnology industries for the identification of lead drugs, perform toxicity tests, screen for antibiotics effects, and carry out functional genomics screens. To date, the platform has been shown to work well for bacterial cells, and yeast.

Innovations and Advantages


Dr. Paulsson and colleagues have developed a microfluidic platform that enables high throughput microscopy-based screening. The platform – named MACS for microfluidics-assisted cell screening - utilizes a soft flexible polymer to trap cells flowing through a channel, once trapped; the cells are imaged and then released. By repeating this process over and over again, Paulsson and his colleagues are able to image thousands of cells each minute, detecting rare events and mutations, which is many more than conventional microscopy typically allows. So far, imaging ability of the machine was tested on both prokaryotes and eukaryotic cells. This device, retaining full benefits of classic microscopy, enables for the first time, the localization of single molecules in cells in combination with high-throughput screening, while most other FACS/imaging methods struggle to even determine the rough size and shape of cells. It also allows for analysis of growth rates via an upstream growth chamber where the culture turbidity can be measured. Some other benefits include: minimal lag time between sample preparation and imaging [thanks to automation], since the device is simply mounted on top of the microscope, it can keep up with improvements in microscopy. Most importantly, the platform is highy flexible and costs a tiny fraction of other devices.

Additional Information


Intellectual Property Status: Patent(s) pending





Inventor(s):
    Huh, Dann
    Landgraf, Dirk
    Okumus, Burak
    Paulsson, Johan

Categories:
For further information, please contact:
Michal Preminger, Director of Business Development
(617) 432-0920
Reference Harvard Case #4494