Synthesis on chip

Chemical synthesis on chip involves dispensing and mixing reagents at a set temperature, pressure, and time and purification of the products. Similarly, analysis on chip also usually starts with chemical reaction of a marker for the sample, followed by separation and detection. The purification and analysis of products on a chip is outside the scope of this discussion. 

Diazo coupling was used to demonstrate the feasibility of organic multi-step synthesis on a chip [4]. This involved showing the safe quenching of hazardous intermediates such as the diazonium salts needed as precursor for that synthesis. Especially, this involves the in situ generation and consumption of such species. 

Fig. 61. Schematic illustrating the on-chip synthesis of DNA oligomers at silicon surfaces. Reproduced with permission from Ref. (196). Copyright 2001, Wiley-VCH.

The field of on-chip solution-phase synthesis and analysis, termed pSYN I AS (miniaturized-SYNthesis and Total Analysis Systems) is a rather new field in or-... 

Chi-I Lang, Synthesis of new, vapor-depositable low dielectric constant materials for use as on-chip dielectrics, Doctoral Dissertation, Rensselaer Polytechnic Institute (1 995). 

An array of oligonucleotide which is composed of 20 80-mer oligos, or peptide nucleic acid probes, is synthesized either in situ (i.e., on-chip) or using conventional synthesis followed by on-chip immobilization. The resultant DNA array is then exposed to the labeled sample of DNA, hybridized, and the identity/abundance of complementary sequences determined. This method was developed at Affymetrix, Inc. and called DNA chips. Today, oligonucleotide-based chips are manufactured by many companies using alternative in situ synthesis or depositioning technologies. 

Microreactor technology offers the possibility to combine synthesis and analysis on one microfluidic chip. A combination of enantioselective biocatalysis and on-chip analysis has recently been reported by Beider et al. [424]. The combination of very fast separations (<1 s) of enantiomers using microchip electrophoresis with enantioselective catalysis allows high-throughput screening of enantioselective catalysts. Various epoxide-hydrolase mutants were screened for the hydrolysis of a specific epoxide to the diol product with direct on-chip analysis of the enantiomeric excess (Scheme 4.112). 

Gao X, Zhou X, Gulari E. Light directed massively parallel on-chip synthesis of peptide arrays with t-Boc chemistry. Pro-teomics 2003 3 2135-2141. 

Oligohudeotide probes (20 to 80-mers) are synthesized either in situ (on-chip) or by conventional synthesis followed by on-chip immobilization Expressed-sequence tags (200r560 bases long)... 

The second platform for DNA microarray fabrication involves controlled in situ synthesis of oligonucleotides (on-chip). This technology, implemented by Affymetrix in the manufacture of GeneChips, uses photolithographic... 

Fig. 7 Peptide synthesis on a PSi microcavity with on-chip optical monitoring (Adapted from [21]). Reflectivity minima indicate successive attachment of chemical species during synthesis (a) bare porous silicon (b) silane linker (c) rink peptide linker (d) arginine...

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