Lab-on-a-Chip

Other Unique Engineering Ideas
An active field is the integration of the sample preparation and DNA array detection in the so-called ‘Lab-on-a-Chip’ configuration. The goal of this technology is to fully integrate multiple processes, including sample collection and pretreatment with the DNA extraction, amplification, hybridization and detection, on a microfluidic platform.

1. Description

2. Why

3. How

4. Future Trends

5. Related Links

Description 

The ability to perform all the steps of the biological assay on a single self-contained microchip promises significant advantages in terms of speed, cost, sample/reagent consumption, contamination, efficiency and automation (including parallel sample processing).Such miniaturization of the analytical instrumentation will enable transportation of the laboratory to the sample source (as desired for point-of-care testing). Sophisticated devices have thus been fabricated with pumps, valves, heaters, filters, along with the corresponding fluidic network.For example, PCR amplification has been performed by continuously flowing the sample through three well-defined temperature controlled zones on a glass microchip. The pattern of the chip layout determined the relative time a fluid element is exposed to each temperature zone. An array of PCR microchips, based on multiple reaction chambers with resistive heaters was developed at the Lawrence Livermore National Laboratory. A microchip device for cell lysis, multiplex PCR and electrophoretic sizing has also been described. Voltages, applied through electrodes placed within the individual reservoirs, are used to drive the electroosmotic flow. Such electroosmotic ‘pumping’ obviates the need for mechanical pumps or valves, with the channel intersections serving as ‘virtual injection valves’.

Why

Lab-on-a-Chip enables sample handling, mixing, dilution, electrophoresis and chromatographic separation, staining and detection on single integrated systems. The purpose of these devices is to manipulate and process solution based samples and systems by carrying out typical procedures such as mixing, heating and separation. Processed samples may be delivered to some form of detector that subsequently transmits data. It is far less expensive than conventional methods of analyzing DNA (which require specialized laboratories, equipment, and personnel) yet just as quick and sensitive.The main advantages of Lab-on-a-Chip are

  • ease-of-use,
  • speed of analysis,
  • low sample and reagent consumption and
  • high reproducibility due to standardization and automation

Microfabricated devices are also attractive for high-throughput electrically-driven DNA separations. For example, Woolley et al. described capillary electrophoresis microchips that allow DNA sizing of 12 samples in parallel with a resolution of 10 bp and higher throughputs than conventional techniques.

How

These devices typically consist of a monolithic material that is patterned with microscale channels and features such as mixers, valves, injectors and separators that can assume the role of equivalent macroscopic laboratory equipment. The preparation of these credit-card sized microlaboratories commonly relies on advanced microfabrication and micromachining technologies, using processes common in the manufacture of electronic circuitry.Appropriate connection to the macroscale world for inputs and outputs (not trivial) is required and so the microfluidic device is likely to be part of a system. Controlled electric fields have been used for discriminating among oligonucleotide hybrids with varying binding strengths (including between complete match and single-base mismatch) and to expel the unhybridized DNA. Such fine-tuned electronic stringency selection obviates the need for extensive washing. The electronically-regulated sample preparation process was demonstrated for the dielectrophoretic separation of Eschericia coli from blood cells. After the isolation, the bacteria were lysed by a series of high-voltage pulses.Routine processing of samples and microreactors for selected chemical reactions are likely to represent some of the earlier applications of microfluidic devices to allow speed, control and reduced cost compared to incumbent solutions. Although the advances in genomics (in which DNA microarrays have played a key role) have been crucial and will continue to play a vital role they only represent part of the life science puzzle.

Future Trends 

On-chip fluid manipulations have been demonstrated for sequentially transporting nanoliter samples through a network of microchannels, mixing of sample and reagents, dispensing of samples, DNA restriction digestion and electrically-driven separations. A variety of microstructures have been proposed for on-chip PCR amplification.The first commercially available product based on microfluidic technology is the HP 2100 Bioanalyzer (Hewlett Packard). This instrument integrates the sample handling and electrophoretic separation.Nanogen Inc. (San Diego, CA) has developed an electronic sample preparation process. The company is addressing each step in the sample-to-result process on microfabricated chip-based devices. This includes the integration of electronic cell separation, electronic sample transport, electronically-accelerated hybridization and electronic denaturation.

Keywords

DNA Analysis, Microarrays, Lab-on-a-Chip, Microfluidic Lab-on-a-Chip.

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