Abstract
Photolithographic micromachining of silicon is a candidate technology for the construction of high-throughput DNA analysis devices. However, the development of complex silicon microfabricated systems has been hindered in part by the lack of a simple, versatile pumping method for integrating individual components. Here we describe a surface-tension-based pump able to move discrete nanoliter drops through enclosed channels using only local heating. This thermocapillary pump can accurately mix, measure, and divide drops by simple electronic control. In addition, we have constructed thermal-cycling chambers, gel electrophoresis channels, and radiolabeled DNA detectors that are compatible with the fabrication of thermocapillary pump channels. Since all of the components are made by conventional photolithographic techniques, they can be assembled into more complex integrated systems. The combination of pump and components into self-contained miniaturized devices may provide significant improvements in DNA analysis speed, portability, and cost. The potential of microfabricated systems lies in the low unit cost of silicon-based construction and in the efficient sample handling afforded by component integration.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnheim N., Erlich H. Polymerase chain reaction strategy. Annu Rev Biochem. 1992;61:131–156. doi: 10.1146/annurev.bi.61.070192.001023. [DOI] [PubMed] [Google Scholar]
- Dietrich W. F., Miller J. C., Steen R. G., Merchant M., Damron D., Nahf R., Gross A., Joyce D. C., Wessel M., Dredge R. D. A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nat Genet. 1994 Jun;7(2 Spec No):220–245. doi: 10.1038/ng0694supp-220. [DOI] [PubMed] [Google Scholar]
- Fleischmann R. D., Adams M. D., White O., Clayton R. A., Kirkness E. F., Kerlavage A. R., Bult C. J., Tomb J. F., Dougherty B. A., Merrick J. M. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496–512. doi: 10.1126/science.7542800. [DOI] [PubMed] [Google Scholar]
- Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
- Harrison D. J., Fluri K., Seiler K., Fan Z., Effenhauser C. S., Manz A. Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip. Science. 1993 Aug 13;261(5123):895–897. doi: 10.1126/science.261.5123.895. [DOI] [PubMed] [Google Scholar]
- Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
- Nickerson D. A., Kaiser R., Lappin S., Stewart J., Hood L., Landegren U. Automated DNA diagnostics using an ELISA-based oligonucleotide ligation assay. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8923–8927. doi: 10.1073/pnas.87.22.8923. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roman C., Matera A. G., Cooper C., Artandi S., Blain S., Ward D. C., Calame K. mTFE3, an X-linked transcriptional activator containing basic helix-loop-helix and zipper domains, utilizes the zipper to stabilize both DNA binding and multimerization. Mol Cell Biol. 1992 Feb;12(2):817–827. doi: 10.1128/mcb.12.2.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Todd J. A. Genetic analysis of type 1 diabetes using whole genome approaches. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8560–8565. doi: 10.1073/pnas.92.19.8560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
- Wilding P., Shoffner M. A., Kricka L. J. PCR in a silicon microstructure. Clin Chem. 1994 Sep;40(9):1815–1818. [PubMed] [Google Scholar]
- Woolley A. T., Mathies R. A. Ultra-high-speed DNA fragment separations using microfabricated capillary array electrophoresis chips. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11348–11352. doi: 10.1073/pnas.91.24.11348. [DOI] [PMC free article] [PubMed] [Google Scholar]