Active CMOS biochip for electrochemical DNA assays

20 21The development of methods and technology to perform genome sequencing and genomic assays has enabled significant advances in biomedical research in the past and will have a profound impact on the areas of disease prevention, personalized medicine, and clinical diagnostics in the future [1]. Over the last two decades, enormous effort from the public and private sectors has been spent on “sequencing” the human genome; that is, determining the exact series of the approximately 6 billion nucleotide base pairs contained in the 46 chromosomes found in most human cells. Ever since drafts of the human genome were first published in 2001 by both the publicly funded International Human Genome Sequencing Consortium through the Human Genome Project (HGP) [2] and a team led by J. Craig Venter of the privately owned biotechnology company Celera Genomics [3], the cost of human genome sequencing has declined by many orders of magnitude due to the introduction of increasingly automatable methods and technology. In particular, shotgun sequencing approaches [4] involving dideoxy chain termination techniques and electrophoretic size separation (known as “Sanger sequencing,” after the individual who developed the technique [5]) have been replaced by massively parallel optical [6,7] and electronic [8] sequencing-by-synthesis platforms. These innovations have brought the cost of human genome sequencing down from US$3 billion, in the case of the HGP [9], to well under US$1 million [8]. Further technological developments will undoubtedly occur until one’s own genome can be sequenced for less than US$1000 [10].