A HIGH SPATIAL RESOLUTION SPECTROGRAPH FOR DNA SEQUENCING

IF THE HUMAN GENOME PROJECT IS TO BE SUCCESSFUL, MUCH MORE RAPID DNA SEQUENCING WILL BE REQUIRED. IT IS ESTIMATED THAT PRESENT TECHNOLOGY IS 100-500 TIMES TOO SLOW TO PERMIT SEQUENCING OF THE ENTIRE HUMAN GENOME BY THE ORIGINAL PROJECTED COMPLETION DATE OF 2005. CURRENTLY, THE MOST SUCCESSFUL TECHNOLOGY EMPLOYED FOR LARGE SCALE DNA SEQUENCING INVOLVES REAL-TIME, FOUR COLOR, FLUORESCENT LINE IMAGING DURING THE ELECTROPHORESIS PROCESS (I.E., THE ABI 373A DNA SEQUENCER). THIS BASIC TECHNOLOGY CAN PROBABLY BE SCALED TO SIGNIFICANTLY HIGHER LEVELS AND IS LIKELY TO REMAIN THE METHOD OF CHOICE FOR FUTURE DNA SEQUENCING. INDEED, A NUMBER OF RESEARCH GROUPS HAVE BEEN DEVELOPING FASTER FLUORESCENCE DNA SEQUENCES. ALTHOUGH GREAT STRIDES HAVE BEEN MADE IN REDUCING ELECTROPHORESIS TIMES (10-20 FOLD), FUTURE GAINS IN THROUGHPUT WILL PRIMARILY DEPEND ON INCREASED MULTIPLEXING. SUCH HIGH THROUGHPUT INSTRUMENTS WILL REQUIRE A DETECTION SYSTEM WITH HUNDREDS OF SPATIALLY RESOLVED CHANNELS. IN PHASE I A COMPLETELY NEW CONCEPT IN HIGH SPATIAL RESOLUTION SPECTROSCOPY WILL BE TESTED. THE HIGH SPATIAL RESOLUTION PERFORMANCE WILL BE ACHIEVED BY EMPLOYING A RADICALLY DIFFERENT APPROACH TO THE DESIGN OF A SPECTROGRAPH. SUCH A SPECTROGRAPH WHEN COMBINED WITH A CHARGE COUPLED DEVICE ARRAY DETECTOR, WILL PRODUCE A SYSTEM CAPABLE OF RAPIDLY RECORDING SPECTRAL SIGNATURES FROM MORE THAN 300 SPATIAL LOCATIONS.