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238 Development of Clinical Automated Multiplex Affinity Capture Technology for Detecting Low Abundance Cancer-related Proteins/Peptides

Number of anticipated awards: 3
(Fast-Track proposals will be accepted.)
Budget (total costs): Phase I: $150,000;
Phase II: $1,000,000

The deadline for receipt of all contract proposals submitted in response to this solicitation was:
5:00 p.m. Eastern Standard Time
Monday, November 6, 2006

Of the hundreds of thousands of proteins believed to be found in different body fluids, it is likely that cancer-related proteins will be in relatively low abundance. The development of effective technologies to accurately measure these proteins and improve our diagnostic capabilities by discerning diseased from non-diseased states requires the development of next-generation proteomic technologies. The purpose of this project is to stimulate the development of quantitative automated affinity/protein capture multiplex technologies for measuring low abundant cancer related proteins/peptides from bodily fluids in support of the Clinical Proteomic Technologies for Cancer initiative. In addition, this tool as conceived is to be applicable in Cancer Centers and other settings where NCI Investigators conduct clinical care.

The application of proteomics tools in the clinical setting lags far behind their use in basic science and drug discovery. In the past, protein/peptide biomarkers were tested individually to determine their value using common techniques such as ELISA, 2-D gels, and mass spectrometry. Each of these technologies has its advantages, but they still suffer from an inability to quantitatively evaluate multiple markers in a single reaction. Multiplexing capability is becoming a critical parameter in clinical biomarker evaluation today, as testing practices employing a single marker do not have the performance characteristics required to enable critical decision making. While some new technologies capable of measuring multiple biomarkers in a single assay has emerged, they typically suffer from low precision (CV's as high as 50%), an inability to detect physiological levels of low abundant proteins, and automation. Despite these shortcomings, the advantage gained by miniaturization, high sensitivity, high-throughput, and automation makes affinity/protein capture technologies a potentially powerful technology for the quantitative detection of known protein markers and the discovery of new markers.

Therefore, the NCI is interested in proposals that focus on developing a quantitative automated high-throughput multiplex affinity/protein capture technology for detecting low abundant cancer related proteins/peptides from bodily fluids (examples of "bodily fluids" include plasma or serum, urine, serous fluids collected from body cavities, saliva, and ductal lavage, but not cell lysates or tissue culture media). Proposals should describe how the proposed technology will be highly specific, highly selective and have ultra-sensitive detection capabilities (at least within the ng/mL range) with limited sample preparation. Proposals should also distinguish any new methods of multiplex fabrication, novel affinity/protein capture systems, and/or new detection/quantification systems. All responses must deliver a reasonable method for working with complex bodily fluids. In addition, maximum level of multiplexing, volume of sample requirement, with sample processing/analysis time must be addressed.

Phase I Activities and expected deliverables:

  • Demonstration of feasibility of the innovative approach.
  • Produce and initial product prototype in working with the Clinical Proteomic Technologies for Cancer community.
  • Conduct usability testing with product prototype with representative users (e.g. Clinical Proteomic Technologies for Cancer community).
  • Make modifications to the prototype based on results obtained from usability testing.
  • Compare findings to ELISA-based technologies. Detection limits should aim to be measured and reported as absolute quantitations that equal or surpass current ELISA measurements.
  • Prototype requirements include sample volumes less than 50 microliters, multiplex a minimum of 5 markers, high sensitivity (detection limit lower than 5 picogram/microliter), high reproducibility (CV's less than 10%), and broad dynamic range (gram/Liter to nanogram/Liter)
  • Establish prototype revisions/additions to be implemented and tested in Phase II.
  • Present findings to an NCI Evaluation Panel.
  • Research should be proposed with quantitative feasibility milestones.

Phase II Activities and expected deliverables:

  • Implement strategy and project plan for a fully functional quantitative, automated high-throughput multiplex affinity/protein capture technology for detecting low abundant cancer related proteins/peptides from bodily fluids.
  • Specificity greater than 95%.
  • Development of an affinity/protein capture technology with multiplexing capability up to 50 analytes (proteins/peptides) that implements the features, functions, and requirements developed in Phase I. Project to be done in conjunction with the Clinical Proteomic Technologies for Cancer community.
  • Validate findings to ELISA.

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