Miniaturized NMR-Compatible Bioreactor and Perfusion System
University of California System: University of California, San Francisco
posted on 04/23/2010
UCSF researchers have developed a high-performance miniaturized bioreactor that fits inside a standard 5mm tube NMR spectrometer. This b ioreactor is ideal for growth of small, valuable cell samples, including stem cells and biopsies and for metabolomics in living cell samples. Applications would include rapid metabolic testing of valuable new chemical entities and personalized medicine.
Suggested Uses
Pharmaceutical and Chemical Industry
· Biologically relevant drug or biomarker design
· Toxicity, safety and efficacy testing of new drugs
· Metabolomics (analysis of new drugs, pesticides and their metabolic products)
Research
· Metabolic studies on live cells, including primary cells and stem cells
· Monitoring of protein synthesis and dynamics, genetic manipulation and biochemical reactions
Health Care
· Biomarkers for prostate cancer or other diseases
o Assays of hyperpolarized metabolism using dynamic HP, NMR, or PET, SPECT, including pyruvate metabolism are being developed
· Personalized medicine
o Testing of drug efficacy on patient biopsies
o Characterization of disease state from patient biopsies
· Regenerative medicine
o Culture and expansion of stem cells and mature tissue grafts
Advantages
· Small volume
· Allows dynamic, non-invasive and real-time studies in living cells
· Compatible with all standard NMRs, no need for specialized machinery
· Superior nutrient perfusion and waste export
· Reusable or consumable
· Ease of use with a “plug and play” design scheme
Detailed Description
Background:
Pharmaceutical toxicology studies include testing the effects of drugs on metabolic processes inside cells. Current state of the art involves extracting the contents of cells, which requires killing each cell sample and repetition of up to 100 independent experiments. Despite this inefficiency, metabolic testing and toxicology are routinely employed by pharmaceutical companies in preclinical studies of new chemical entities. Non-invasive assays of primary human cells would be faster, more efficient, and more representative of in vivo metabolism.
To solve this problem, researchers and engineers have spent years to develop a bioreactor which could be placed inside of NMR or MRI systems to assay metabolism in living cell cultures. Such first-generation bioreactors, which are not commercially available, are compatible only with the larger 10-25mm NMR coils and require 100-200 million immortalized cells, effectively preventing use with rare or valuable cell types such as stem cells, primary cells and tissues, or patient biopsies. Smaller NMR-compatible bioreactors would allow in vivo metabolic studies on living cultures of stem cells, primary cells and tissues, and biopsies and open the door for a variety of new applications.
Description:
UCSF investigators have developed and tested a new miniaturized NMR-compatible bioreactor. This device can be used to place live cells and tissues inside the 5mm coil of a standard high-resolution NMR spectrometer. The UCSF bioreactor is compatible with any standard NMR spectrometer and can be used to assay metabolism in small volumes of valuable primary cells, stem cells, or patient biopsies in real time. The system was designed for the stringent requirements of NMR, but it is fully compatible with other non-invasive imaging modalities, including PET, SPECT and fluorescence.
The UCSF 5mm bioreactor currently requires only 5-10 million cells and performs better than 10-25mm bioreactors. Compared to larger bioreactors, the UCSF 5mm bioreactor produces NMR spectra with improved signal to noise ratios and sharper peaks. Cells remain healthy and proliferative and cultures have less than 1% apoptotic cells. The bioreactor can be completely sterilized and re-used or could be a consumable bench-top device where the chamber can be replaced.
File Number: 20838
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This innovation currently is not available for online licensing. Please contact Dior Baumjohann at University of California System: University of California, San Francisco for more information.
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