Tools For DNA Diagnostics (October 1994)

Miniature Integrated Nucleic Acid Diagnostic (MIND(TM)) Development

Sponsor: Affymetrix, Inc.

• Project Performance Period: 2/1/1995 - 1/31/2000
• Total project (est.): $62,965,000.00
• Requested ATP funds: $31,478,000.00

Affymetrix and Molecular Dynamics propose a joint research venture to develop a Miniature Integrated Nucleic Acid Diagnostic (MIND^Tm) device, suitable for use in hospitals, clinics, or doctors' offices, to provide rapid, accurate diagnosis of a wide variety of diseases. The basic MIND device is envisioned as a hand-held unit, perhaps 10 centimeters by six, which will accept a small sample of whole blood, extract DNA from the blood cells, amplify the DNA sample by a well-established amplification technique, and analyze the resulting sample through two techniques -- DNA probe-array hybridization and capillary-array electrophoresis (CAE). The DNA probe array builds on existing technology developed by Affymetrix to make and build "DNA chips" with thousands of complementary oligonucleotide sequences. CAE is a promising new technique for quickly separating and sizing DNA fragments, but research is needed to develop CAE for use in a compact, reusable system. In addition to the basic MIND unit, a desk-top MIND Reader^Tm unit will read the assay results from MIND devices, analyze the data, and determine a clinical diagnosis. (Future versions of the technology may incorporate the reader functions with the basic MIND device in a single small, highly integrated unit.) R&D challenges include integrating the several sample-preparation stages with the CAE and DNA-probe devices in a single cassette or silicon-chip unit; developing compatible reagent systems for sample preparation; developing tools to correlate genotype and phenotype; achieving single-base resolution in a low-cost CAE device; developing quantitative assay techniques; eliminating the need for the DNA amplification step; and developing an entirely new class of gene assays based on using modified DNA as an electrical conductor and electron-transfer dyes to discriminate perfect DNA matches from mismatches. Early prototypes will be designed to detect drug-resistance mutations in HIV-1, and DNA structures associated with fragile- syndrome and Duchenne's muscular dystrophy. Lawrence Livermore National Laboratory, Stanford University, the University of California (Berkeley), the California Institute of Technology, and the University of Washington also will work on the project.

For project information:

Holly A. Hartz, (408) 731-5721
holly_hartz@affymetrix.com

Active Project Participants

• Amersham Biosciences (formerly Molecular Dynamics, Inc.) (Sunnyvale, CA)
  [Original, Active Member]
  

ATP Project Manager

Douglas Bischoff, (301) 975-8597
douglas.bischoff@nist.gov