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Development of Low Cost, Small Sample Multi-Analyte Technologies for Cancer Diagnosis, Prognosis and Early Detection



Cancer is recognized as a multistep process involving multiple genomic and epigenomic alterations that occur in multiple phases. The complexity of cancer requires multivariate assays for accurate diagnosis, prognosis and treatment monitoring. Recently, two multivariate gene-expression assays, Oncotype DX and MammaPrint, have been developed for determining whether chemotherapy is necessary for breast cancer. The Oncotype DX analyzes the expression of a 21-gene signature by TaqMan RT-PCR. The MammaPrint microarray which measures the expression of 70 breast cancer genes as a signature, provides information about the likelihood of tumor recurrence and guides treatment.

Given the multivariate and heterogeneous nature of the disease, it is likely that the early detection and diagnosis of cancer will be based on multiple analytes. However, the currently available clinical multi-analyte technology platforms have many limitations, including the requirement of multiple biopsies and special specimen collection/storage process. Additionally, their processes are often slow, complex, labor intensive and with sup-optimal sensitivity. These factors contribute to the added cost which also limits their broad applicability. For example the current list price of both Oncotype DX and MammaPrint are over $4000 per sample.

While the various NIH and other Government (DOD, DARPA, NSF, NASA, USDA etc) programs are developing new cutting edge technologies, their focuses are not on commercialization, and these novel technologies have not penetrated into clinical use. This contract topic seeks to promote the development of such innovations in early detection and diagnostic technology to facilitate the commercialization of low cost, efficient multi-analyte technologies with optimal sensitivity for cancer early detection, diagnosis and prognosis. In particular, this topic requests the development of technologies that can obtain multi-analyte molecular information from small volume clinical specimens (e.g. core biopsy, fine needle aspiration, circulating tumor cells or FFPE sections). In addition, this contract topic encourages proposals based on improving both early detection and diagnosis of cancer from easily accessible samples (e.g. blood, sputum, urine, fecal) with low abundant cancer markers.

Project Goals:

The short-term goal for the project is to develop working prototypes of low cost devices or methodologies for multi-analyte analysis of small samples or easily accessible samples with low abundant cancer biomarkers. Long-term goals are to improve cancer early detection, diagnosis, prognosis and treatment monitoring by developing low cost, more efficient, and more sensitive devices or methodologies for multi-analyte detection and analysis. Additionally, this topic requests the development of technologies that can be used with small volume, small numbers of cells or low cancer biomarker abundant clinical specimens obtained through regular biopsy procedures (e.g. core biopsy, FNA), surgery (e.g. FFER sections) or minimally invasive methods (e.g. blood, sputum, urine, and fecal). The technology should be innovative and make use of recent advances in areas such as microfluidics, nanotechnology, multichannel imaging, and transducer technologies for biosensors including optical, electrochemical, piezoelectric, Field Effect Transistor, cantilevers or any other rapid multi-analytes transducers. These devices and methodologies should be more cost efficient than current ones (>5x cost reduction), have significantly improved sensitivity/specificity (>10x) and can be used with samples obtained from single core biopsy or FNA. Acceptable devices and methodologies should be able to analyze at least 30 markers (DNA, RNA, RNAi, or proteins) simultaneously within four hours. If the innovation includes an integrated device, the cost of the market ready device should be less than $15,000. Ideally, the input for the device should be core biopsy, FNA or any small clinical biopsy specimen and the output should be the profile of the markers. This solicitation also encourages developing non-invasive biomarker based technologies and available multi-analyte technologies and assays for cancer early detection.

Accepted devices or methodologies include, but are not limited to:

·       Rapid sample preparation and multi-analyte concentration technologiesfor high quality DNA/RNA RNAi/protein/cell

·       Multi-analyte amplification technologies for DNA,RNA, ncRNAs, RNAi, proteins, and glycoproteins

·       Low-frequency mutation analysis (e.g. for multiple relevant genetic markers/mutations)

·       Rapid DNA sequencing (e.g. for multiple relevant genetic markers/mutations)

·       Advanced PCR techniques

·       New protein or DNA/RNA/ RNAi labeling and label free technologies. Preference will be given to label free technologies

·       Point of Care DNA, RNA or antibody microarrays

·       Automated integrated system

Phase I Activities and Expected Deliverables:

·       Development of the essential components of the proposed technology.

·       Demonstration of the feasibility of the technological innovation (e.g. spiking relevant body fluids with cancer cells or using FFPE). The offer should include benchmarking studies against current technologies. When possible, material that requires IRB approval to acquire or study should not be used for phase I.

·       Characterization of the variation, reproducibility and accuracy of the method.

·       Provide NCI with a detailed report of the number of cells and sample size needed, potential biomarker panels for the technology, estimations of sensitivity, selectivity, the cost of producing the proposed devices and/or reagents, including an analysis/breakdown of vendors and/or sources of raw materials.

Phase II ActivitiesandExpected Deliverables:

·       Develop a prototype of the device or analytical tool incorporating the technology demonstrated in Phase I including automation, software and data analysis.

·       Test the device with clinically relevant cancer biomarkers.

·       Test with a sufficient number of patient samples in several laboratories to demonstrate concordance, clinical utility and advantages, with an appropriate consideration of statistical significance.

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