Abstract
Laboratory science could soon be performed on a chip. Nanotechnology, or more properly termed, microfabrication, makes it possible to create a complete analytical system that will fit into a single test tube. Pipettes, test tube racks, discrete instruments, and mounds of printed output will be relegated to the dusty basement. Mark A. Burns (in the laboratory of David T. Burke) has published a notable success in analytical laboratory microfabrication, (Science, volume 282, page 484–487, 1998). Their integrated nanoliter device can now perform a complete PCR with capillary electrophoresis and fluorescent detection in a device that measures 47mm by 5mm. The potential of these devices to revolutionize clinical diagnosis, bio-warfare detection, food monitoring and pharmaceutical discovery is astounding.
Following the successes of Caliper (Palo Alto, CA, USA), Affimetrix (Santa Clara, CA, USA), Nanogen (San Diego, CA, USA), Orchid (Princeton, NJ, USA), Micronics (Seattle, WA, USA), and others in demonstrating practical utility of their chips, there is little doubt that the miniaturized laboratory has arrived. However, do alternatives exist to the use of microfabrication for high throughput applications? Tom Astle (Tomtec, Inc., Hamden, CT, USA) describes a continuous tape-based ultra high throughput screening system that will be capable of screening over 100,000 compounds per day (see page 31). Similarly, Axiom (San Diego, CA, USA) has developed a flow cytometer that can screen potential therapeutic targets at a similar high throughput rate. The dilemma faced by many pharmaceutical companies investing in screening technologies is whether their investments should be chip-based or custom designed devices such as described by Dr. Astle. On the one hand, chip technologies will have virtually no development costs, but will have a high unit cost. Custom fabricated devices will have a large development cost, but much lower cost per reportable result compared to chips (at least for the first available chips). Clinical laboratories are even further behind the development of microfabricated devices because of their dependence on diagnostic companies for the production of quality reagents. Clinical laboratories are likely to use diagnostic chips only if the price is competitive with today's analytical systems.
Whichever pathway is chosen by the laboratory, chip based or custom designed automated system, there will always be the difficulty of reducing the volume of specimens from their initial large volume to the microscopic scale. We are beginning to see hybrid systems that can deal with specimen preparation in a macroscopic world (e.g. isolated viral particles from 10 mL of patient blood, or obtaining a few micrograms of a test compound from a library). For example, Orchid describes their Chemtel Chip™ reservoir system that provides for the use of a liquid handling robot to deliver reagents and drugs directly to the chip (page 54). Cepheid (Santa Clara, CA, USA) can take direct specimen input since onboard processing integrates directly with the analytical PCR (see JALA 3–6), 1998, page 22).
It is imperative that laboratorians understand the capabilities, costs, and benefits of microfabrication in order to be informed about the potential usefulness and cost benefit of these exciting new tools. The Association for Laboratory Automation is launching smallTalk, a microfabrication conference at the Hilton du Jolla Torrey Pines in San Diego, California on June 20–22, 1999. smallTalk will be the world's most comprehensive non-profit analytical microfabrication forum. Investigators are encouraged to bring their analytical challenges to smallTalk to determine if chip based technology or custom designed automation is the proper choice.