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Ultra high-resolution protein fingerprinting of biopsy samples by mass spectrometry


Fingerprinting Diseases

The Situation: The current resolution of MALDI mass spectral imaging is inadequate for comprehensive protein profiling of small tissue or cellular samples. Sample preparation takes hours and expensive instrument is required. Moreover, results are not reproducible due to poor sample preparation methods.

Our Solution: We have developed a novel MALDI sample preparation method that enables high-resolution protein profiling up to 1-micron level. The technology increases spatial resolution by fifty times, while reduces sample preparation time and costs by a hundred times over existing processes. Our invention allows rapid and accurate fingerprinting of a biopsy sample, therefore will revolutionize disease diagnosis in the future.

Background

Matrix-Assisted Laser Desorption Ionization (MALDI) is an ionization technique often used for mass spectrometric analysis of large biomolecules, such as proteins. Direct mass spectrometry analysis of a tissue sample affords a wealth of chemical information, providing a molecular landscape of a tissue. Mass spectrometry imaging provides spatial and chemical information on hundreds of molecules at a time, providing a better correlation between molecular composition and disease pathology, and therefore a more accurate diagnosis. However, current resolution of MALDI mass spectral imaging is in the range of 1 mm, much too low for comprehensive protein profiling of small tissue or cellular samples.

Applications

  • This invention is a unique tissue preparation method for MALDI mass spectrometry which allows the generation of ultra-high resolution 2-D protein profile of biopsy samples and provides a cost-effective means for accurate early diagnosis of diseases.

Advantages

  • 5-minute sample preparation time for ultra high-resolution Mass Spectrometer analysis.
  • Low running costs: working prototype costs only $6 per sample.
  • By incorporating with existing MALDI mass spectrometry instrumentation and statistics method, this technology will prompt rapid and accurate diagnosis of a wide range of diseases as well as leads for new drugs to combat them.
  • Through existing medical partnerships with Harvard Medical School, we are building a comprehensive disease fingerprint database by comparing patient biopsy samples with normal tissue samples. Such database will be invaluable for developing early-stage diagnostics and therapeutics for cancer, neural degenerative diseases, and infectious diseases.

Technology

We developed a method for the preparation of frozen tissue sections for use in MALDI mass spectrometry imaging, and this is the first such process that is compatible with existing histology procedures routinely employed by pathologists for diagnosing diseases. In this process, a matrix, which is usually a small acid that crystallizes on the surface of a tissue sample, is incorporated directly into the tissue during the tissue fixation process. This new concept method prevents proteins from moving or diffusing from their original location, therefore allowing high-resolution mass spectrometry images to be produced.

Patent Status

  • Patent pending in United States
  • Pending international patent application

Inventors

Jeffrey Agar and Nathalie Agar.

To discuss this technology with a licensing officer, please call Irene Abrams at (781)-736-2176 or email iabrams@brandeis.edu and ask about record ID: 2006-0501.