What is DNA chip? Micro-Array containing all the genes (roughly 40,000) in the entire Human Genome (complete Genetic Code). Each known gene or “probe” occupies a particular “spot” on the chip, and varying levels of fluorescent activity show varying levels of gene activity in introduced genetic material. By introducing these samples or “targets” we can determine which genes are most active for traits, immunities, or any hereditary condition including disease.

History Genetics started in 1866 when a monk named Gregor Mendel discovered biological elements called genes that were responsible the possession and hereditary transfer of a single characteristic. Genes were linked to DNA, but it took James Watson and Francis Crick deduced the double helix structure of DNA in Most recently, the joint venture of the Human Genome Project and a company called Celera published the first draft of the human genome in February 2001.

The Power of Micro-Arrays Micro-Arrays quickly show the relationships between specific genes and specific traits, diseases and the like. Thus, we efficiently gain valuable insight into how our genetics specifically affect us.

Background on DNA To truly understand Deoxy-RiboNucleic Acid(DNA) chips, we must first understand the elegance and complexity of DNA and genetics.

DNA Structure and Nomenclature Double Helix Four Bases

Applying DNA Principles to Chips Chips are designed to either “sequence” or decode genetic strands, or to find genetic matches. HYBRIDIZATION The array provides a medium for matching known and unknown DNA samples based on base-pairing (hybridization) rules. The two strands basically combine automatically if correct matching has occurred.

Chip Mechanisms

The Human Genome Intended to produce a DNA sequence representing the functional blueprint and evolutionary history of the human species Identify all of the approximately 30,000 genes in human DNA Determine sequences of 3 billion chemical base pairs that make up DNA Expensive arduous process - Eleven years, three billion dollars Applications in diverse biological fields: molecular medicine microbial genomics bioarcheology DNA identification bioprocessing

Functional Genomics Thousands of genes and their products in a given living organism function in a complicated and orchestrated way that creates the mystery of life Whole picture of gene function is hard to obtain in varying one gene per experiment Simultaneously analyzing expression levels of a large number of genes provides the opportunity to study the activity of an entire genome The DNA Chip permits these kinds of analyses

Manufacturing Oligonucleotide Arrays MEMS processing technologies Photolithography removes DNA terminators Nucleotide adds itself to exposed strand DNA is constructed in situ Process requires several masking steps Substrate Mask UV Light

Manufacturing Oligonucleotide Arrays OOO O O O OH O O O O O O TT T T C O C TT GCTGCT GGCGGC TAGTAG ACCACC ATTATT CATCAT T O O O TT 3 Masking / DNA Development Process 1 2

Array Hybridization Single strand oligonucleotides stand on the chip Hybridization occurs in complementary strands Each microarray dot contains millions of identical strands Single strands in the area of a microarray dot Strands hybridize Noncomplementary strands in other regions of the chip do not hybridize Information from millions of strands in single dot

Laser Induced Fluorescence Laser Induced Fluorescence (LIF) Principle: Shine Laser on the Die LASER Sense the fluorescent light emitted by the die with diode and analyze data with computers

Array Analysis Laser Induced Fluorescence (LIF) How is this used in data acquisition Read: 1.Color 2.Intensities This requires very sophisticated computer analysis

Proposed Chip Concept “Wet” and “Dry” Chip set-up Principle Combination of Biological and Electrical chips Nano DNA Array Circuitry A

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