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Technical Briefs |
1 Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, 3400 Spruce St., Philadelphia, PA 19104;
2
The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 310-C Abramson Pediatric Research Center, 34th St. and Civic Center Blvd., Philadelphia, PA 19104
aauthor for correspondence: fax 215-662-7529, e-mail kricka{at}mail.med.upenn.edu
We now present the third, and final, part of our series of all-language literature surveys on microanalytical devices. It categorizes and lists books, book chapters, reviews, editorials, papers, abstracts, and patents on the topic of analytical microchips that have been published up to the middle of 2001. It is intended to serve as a convenient entry point into the microchip literature for those wishing to gain an insight into the scope and diversity of this important and rapidly expanding branch of science. The database has been compiled from searches of OVID Medline, INSPEC, BIOSIS, PubMed, various patent databases, and the personal databases of members the IFCC Working Group on Nanotechnology. The listing of references for each of the 18 categories and the combined database can be found at Clinical Chemistry Online (http://www.clinchem.org/content/vol48/issue9/). Previous surveys focused on microarrays (1) and nanotechnology (2), and the databases can be found at www.clinchem.org/cgi/content/full/47/8/1479/DC1/12 and http://www.clinchem.org/content/vol48/issue4/, respectively.
An analytical microchip is a miniature analyzer that has at least one micrometer-sized component [e.g., microchannel, microchamber, or microfilter; for recent reviews of this topic, see Refs (3)(4)(5)(6)(7)(8)(9)]. This type of device is made from various materials, including silicon, glass, plastic, or combinations of glass and silicon, using techniques adapted from the microelectronics industry (e.g., photolithography) and the plastic fabrication industry (e.g., embossing, electroforming, and molding). Components that make up a microchip are bonded together by anodic bonding (glass to silicon), thermal bonding (glass to glass), and solvent bonding (plastic to plastic) processes. Surface chemistry effects are a specific concern in devices with very high surface-to-volume ratios, such as microchips, and there is increased attention to surface properties (e.g., functionalization and texturing) and treatments (e.g., thin films). Most analytical microchips have been produced in silicon or glass, but an important trend is to make these devices out of plastic [e.g., poly(dimethylsiloxane), polymethylmethacrylate, polyimide, and polycarbonate] and so exploit the vast range of materials and low-cost, high-volume manufacturing techniques available for polymers.
Microchips have been designed for a range of chemical and biological analyses based on chromatography, electrophoresis, immunoassay, and nucleic acid target and probe amplification (e.g., PCR and the ligase chain reaction). They have also been very effective for cell isolation and selection by use of microfiltration or electrical fields, and the popular Coulter counter and flow cytometer have been successfully miniaturized into a chip format (10)(11). Microchip components are also gaining popularity for sample application in electrospray mass spectrometric methods (12).
An important advantage of the microchip approach to analysis is integration of successive steps in an analytical process (e.g., sample preparation, analytical reaction, and detection) on a single microchip or a multilevel microchip to produce a miniaturized total analytical system or a lab-on-a-chip (13). The scope of micromachined components available for incorporation into a lab-on-a-chip is diverse and includes pumps, valves, fluid channels and chambers, thermal control systems, sieves, and filters.
Key to the development of this new type of analyzer has been refinements of microfabrication techniques, development of convenient microchip-user interfaces, and a better understanding of microfluidics. Different types of microfabricated on-chip valves and pumps have been designed, and flow within chips can also be controlled by electrokinesis. An advantage of the latter option is that there are no moving parts, only the electrodes that are used to control flow. A particular concern for microchips has been the efficiency of mixing within submicroliter chambers and channels. New modeling software allows simulation of flow within microchips, and hence design optimization, before microchip fabrication (14).
Rapid progress is being made in the commercialization of microchips, particularly microchips for capillary electrophoretic separation of DNA and proteins as well as DNA analysis [see Ref. (15) for a compilation of companies active in analytical microchips]. Already there are indications that microchip analyzers are replacing existing analyzers and techniques (e.g., microchip capillary electrophoresis replacing conventional gel electrophoresis for DNA sizing), and further commercialization will hasten this process.
We divided the microchip literature into four major topic areas and subdivided these into a series of 18 categories. Documents in each category are listed in chronologic order and in alphabetic order of first author within each year. Table 1
provides a list of key words for each category to provide a more detailed view of the scope of each of these sections. The key words reflect the most important topics within each category. In the interest of simplicity, citations have been assigned to just one category. A more detailed and comprehensive listing of references for particular topics can be obtained by searching the online database (including title, keywords, and abstracts) using the appropriate keyword or keyword combinations. We have provided the total database and the database for the different categories for the convenience of the user [available through Clinical Chemistry Online (http://www.clinchem.org/content/vol48/issue9/)]. Please note that in many cases we have relied on the abstraction service for the citation details. The Internet is also a rich source of information on microchips, and the reader is directed to the excellent DNA Microarray (Genome Chip) web site (15), which lists many aspects of microchips science and business.
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This compilation is based in part on a survey undertaken by the IFCC Working Group on Nanotechnology, chaired by Dr. Larry J. Kricka. Members of the Working Group are listed in the data supplement that accompanies this Technical Brief at Clinical Chemistry Online (http://www.clinchem.org/content/vol48/issue9/).
Footnotes
1 current address: Christ’s College, Cambridge CB2 3BU, England 
References
The following articles in journals at HighWire Press have cited this article:
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  L. J. Kricka, T. Joos, and P. Fortina Protein Microarrays: A Literature Survey Clin. Chem., December 1, 2003; 49(12): 2109 - 2109. [Full Text] [PDF]
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