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CELLS-ON-A-CHIP: Apparatus for Real-Time and Label-Free Molecular Imaging of Live Cells and Bacteria

JIB-2201

APPLICATIONS OF TECHNOLOGY:

  • Biomedical research
  • Antibiotic development
  • Technological improvements in
    • Biofuels and other forms of renewable energy
    • Bioremediation of contaminated soil and water
    • Maintenance of soil and water ecosystems (via communities of bacteria, e.g., biofilms)
    • Carbon sequestration methods through marine biological systems (e.g., microscopic algae)
  • Macromolecule interactions (e.g., protein-DNA or protein-protein interactions)

ADVANTAGES:

  • Enables the study of live single or multiple cells in real time for more than 24 hours
  • Provides a broader spectrum of molecular information about cells’ responses to drug exposure, changes in temperature, or nutrient levels
  • First device to combine microfluidics with infrared microscopy
  • Direct micro-manipulation of cellular/tissue and injection directly into live cells
 
 

 

A schematic diagram of the Cell-On-a-Chip technology.

ABSTRACT:

To identify stem cells for the development of more effective cancer therapies, or to noninvasively determine molecular and chemical changes in living microorganisms, industry has relied on fluorescent or radioactive tags to observe the behavior of biomolecules associated with tumors or bacterial infections. These techniques require non-native molecular contrasting agents such as fluorescent dyes, quantum dots, radioactive labels, or genetically engineered cell lines that often alter cellular physiology.

As an alternative, researchers at Berkeley Lab and Livermore Lab have created the first label-free diagnostic and imaging tool for the real-time biochemical measurement of live cells (single or multiple) or live tissues undergoing changes in response to stimuli from either within the cell (e.g., radicals or aging) or outside the cell (e.g., toxins, pathogens, or radiation). This unique “Cells-on-a-Chip” apparatus continuously sustains cells for more than 24 hours in a very thin (less than 10-micron) liquid medium that moves around the cell’s surface delivering nutrients to the cell while simultaneously removing cellular waste. The continuous system, which may be programmed to automatically adjust culture conditions, is the first to successfully combine a microfluidic device with infrared microscopy. Furthermore, its open-channel flow configuration allows the direct micro-manipulation of cellular/tissue systems (e.g., biomolecules such as DNA or RNA) and the use of needles to inject drugs or chemicals (such as toxins) directly into live cells.

The apparatus is based on infrared light interaction with cellular molecules and designed to minimize the water absorption during mid-infrared spectroscopy. It can be used for the infrared imaging of living cells or tissues as they respond to a cancer cell, cancer drug, or antibiotic. Prior to this invention, using infrared for tracking real-time changes in biomolecules and chemistry within living cells or tissue had been a challenge, as the liquid growth medium required to study living organisms over long periods of time tends to strongly absorb the mid-infrared light.

The invention can also be used for the improvement of existing methods for real-time in situ observations of fetal cells, tumor/cancer cells, or stem cells, and in vitro diagnostics of diseased cells (e.g., cancer cells, pathogens, HIV/AIDS).  It facilitates study of topics such as how bacteria develop antibiotic resistance over time or it can be used to monitor cancer cells’ responses to cancer therapies. The apparatus additionally promises to be useful in the bioremediation of contaminated soil or water, the advancement of plant- and microorganism-based carbon sequestration solutions to global warming, the maintenance of the soil or water ecosystem, and the development of biofuels and other forms of renewable energy.

STATUS:

  • Patent pending. Available for licensing or collaborative research.

To learn more about licensing a technology from LBNL see http://www.lbl.gov/Tech-Transfer/licensing/index.html.

REFERENCE NUMBER: JIB-2201

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Last updated: 08/12/2013