The ever-shrinking laboratory - Part 2
To make such devices, chemists are adapting techniques used in the microelectronics industry, i.e. microlithography and micromachining, for squeezing millions of transistors on to a silicon chip. Similarly, chemists have been able to etch narrow channels and conduits on slivers of glass and plastic to form chemical mixing and separating systems for tiny samples. Several thousand channels can be packed into a single chip and electrodes fed in while nanolitres or less of a sample are sucked or pumped into the system. The channels, which are up to 50 hundredths of a millimetre wide, are a fraction of a hair's width across so fluids flow by capillary action.
However, electrical probes can be used to 'drive' materials such as solvent and chemical sample down particular capillary channels so that they mix at specific points in the chemical 'circuit'. The speed at which different chemicals move in an electric field will depend on their electrical charge, molecular weight and other properties so tiny amounts of different products, such as protein fragments or DNA, can be tapped off from the capillary one after the other even in a complicated mixture. By using fluorescent markers the researchers can 'see' the molecules emerge using a detector unit, which itself might be just a centimetre square and hooked up to a computer.
The UK's 'lab-on-a-chip' (LOC) consortium coordinated by Stephen Haswell of Hull University hopes to make the UK the leader in the field. Its members include research groups led by, Andreas Manz at Imperial College London, chemical engineer Ron Pethig's group at Bangor University, Jonathan Cooper of the Bioelectronics Research Centre at the University of Glasgow and teams at the universities of Hull, Cardiff and Newcastle and UMIST. Companies such as Unilever, GlaxoWellcome, Epigem, Kodak, Faraday Foresight NW, Optokem, Windsor Scientific, Kalibrant, MSTB and the Laboratory of the Government Chemist (LGC) also form part of the consortium.
The total budget for the project is likely to be
about GBP3.2million (US$5.34m) of which the UK Government is contributing
GBP1.33million (US$2.22m( and the remainder coming from the industrial partners. One of the main aims of the LOC consortium in developing analytical and synthetic lab-on-a-chip devices is to ensure the kits are compatible so that devices can be integrated like 'plug-and-play' computer components.
Manz and his colleague Andrew de Mello have recently built an LOC chemical amplifier, which converts a few strands of DNA into many more using the polymerase chain reaction (PCR). The sample containing a small amount of DNA is pumped through a single channel in the chemical microchip and passes through different temperature zones, which repeatedly heat and cool the DNA. This process doubles the number of DNA molecules. In the normal-size laboratory, this is a slow process taking ca three hours to achieve amplification of the DNA to detectable concentrations. Manz's ‘LOC’ amplifier can get to the same levels in
90 seconds.
In the US, Fred egnier and his colleagues at Purdue University in Indiana have built a micro-mixing device with an internal volume of just 100 picolitres. This is built up of criss-crossed channels 5 micrometres across. The channels form a tiny whirlpool of 2 picolitre volume as the materials mix under the action of an electric current. Such mixers will be central to many LOCs.
Microscale reactor plants were first thought of in the 1970s by scientists at ICI. But only now are chemists realising the advantages. The main impetus comes from safety, health and environmental issues as well as the possibility of distributed manufacturing so that large-scale plants involved in transporting and handling huge volumes of often hazardous liquids will become obsolete and replaced by small units that synthesise chemicals on demand.
Ray Allen and his group at Sheffield University, for example, have recently demonstrated the conversion of methane to methanol in a microreactor. Allen's team has built a silicon membrane microreactor - an LOC on a board - that operates at medium temperatures. Significant quantities of methanol can be produced quickly and simply by adding more boards to make a reactor block rather than increasing the volume of a reaction flask. This work is an important starting point for the development of microscale reactions such as the oxygenation of hydrocarbons to produce alcohols, anhydrides and ketones, all useful industrial reactions.
The main advantage of microreactor systems would ultimately be safety. Since each microreactor in a chemical plant would only carry a small volume of materials at a time the risk of serious explosion if things go wrong is greatly reduced. Contrast that with a thousand-litre steel flask whose contents are being boiled under pressure. In addition, if a board breaks down it can be pulled out and replaced quickly without interrupting the overall process.
Many chemists hope that the lab-on-a-chip will do for chemistry what the silicon chip integrated circuit did for electronics. While there is admittedly
a lot of hype surrounding the technology, laboratory equipment will inevitably shrink and become much cheaper and
better. We will in the next few years begin to see consumer devices too, for chemical analysis, which will become commonplace in the home, at the doctors' surgery and in the workplace where tests can be carried out quickly and easily for all kinds of compounds of dietary, medical and environmental importance.br>
SSome of the growing list of potential devices that may be possible with
shrinking technology...Medical diagnostics kits...Chemical analysers...Genomic
tests...Environmental test kits...Mini-vital signs monitor...Pocket chemical
factory...