Chip-based laboratories

Caliper Technologies Corporation, Palo Alto, California, is working toward creating a miniature chemistry laboratory about the size of a toaster that can be used with plug-in chip-based laboratories. Various chips would be furnished with the unit that would be appropriate for different types of analyses. The entire unit would be connected to a computer to collect and analyze the data. There is even the possibility that these laboratories could be used in the home to perform analyses such as blood sugar and blood cholesterol and to check for the presence of bacteria such as E. coli and many others. This would revolutionize the health care industry. ... 

The so-called micro-total analytical systems (/tTAS) can integrate sample handling, separation, and detection on a single chip [9]. Postcapillary reaction detectors can be incorporated as well [10]. Fluorescence detection is the most common method employed for these chip-based systems. A commercial instrument (Agilent 2100 Bioanalyzer) is available for DNA and RNA separations on disposable chips using a diode laser for LIF detection. In research laboratories, polymerase chain reaction (PCR) has been integrated into a chip that provides size separation and LIF detection [11]. 

The future technological advances in drug discovery will likely involve separation sciences, MS, and hyphenated techniques. More detailed discussions on the technology development and future trends in bioanalysis, laboratory automation, and MS instrumentation have been elaborated in other chapters. Therefore, only three technologies are specifically addressed with regard to their potential application in drug discovery pSFC monolithic column technologies and chip-based separations. 

Lab-on-a-chip (LOG) and lab-on-valve (LOV) devices are versions of pTAS where fluids are manipulated to give a complete assay on a microfabricated chip. Their main goal is the scaling down of laboratory processes onto a chip-based platform. 

DRE Suffield is also investigating the use of CE and CE-Laser Induced Fluorescence (LIF) Detection for ultra-high sensitive analysis under field laboratory conditions. Some specific applications for highly polar, water soluble molecules, such as proteins, peptides and toxins, have been developed. DRE Suffield, in cooperation with the University of Alberta, is also developing miniaturized, silica-chip based CE instrumentation and field portable CE-LIF instruments for detection and identification of biological and chemical warfare agents. 

E. Ghafar-Zadeh, M. Sawan, Charge-based capacitive sensor array for CMOS-based laboratory-on-chip apphcations, IEEE Sensors Joiunal 8 (2008) 325-332. 

MS has been used to characterize 2DGE- and LC-separated human pituitary proteins and DEPs that are related to human pituitary adenomas [2,12,15-17]. PTMs of proteins are also important to study. MS/MS effectively characterizes the PTMs and determines the modified sites. LC-ESI-qlT MS/MS has been used to identify the phosphorylation [18] and nitration sites [19-21] of proteins in the human pituitary proteome. A human pituitary proteome reference database has been established in our laboratory [12,15], many tumor-related proteins were identified [2,17]. And the primary structure and PTMs of pituitary proteins were MS-characterized [2,12,15-21], Those data could contribute to the basic and clinical research studies of human pituitary tumors. Moreover, novel protein chip-based MS technology [22] might eventually be used for the screening, diagnostics, and therapeutics of human pituitary diseases. 

The current trend in analytical chemistry applied to evaluate food quality and safety leans toward user-friendly miniaturized instruments and laboratory-on-a-chip applications. The techniques applied to direct screening of colorants in a food matrix include chemical microscopy, a spatial representation of chemical information from complex aggregates inside tissue matrices, biosensor-based screening, and molec-ularly imprinted polymer-based methods that serve as chemical alternatives to the use of immunosensors. 

Protein toxins such as botulism, staphylococcal enterotoxin B, or ricin can be separated with gas or liquid chromatography, electrophoresis, or a combination. The pChemLab (Sandia National Laboratories Albuquerque, NM) series of instruments includes a hand-held Bio Detector. Proteins in the sample are labeled with fluorescent tags, and nanoliter volumes of samples are separated by microchannels etched into a glass chip. The separation occurs as the sample moves through the channels and identification is based on retention times. The analyses can be completed within 10 min. 

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