This symposium, which took place on September 11 was organised in association with the Joint Pharmaceutical Analysis Group of the Royal Pharmaceutical Society and the Royal Society of Chemistry and was chaired by Dr Howard Hill (Huntingdon Life Sciences)
Five speakers presented their views on the current applications of silicon
chip technology to pharmaceutical chemistry, ranging from its use in
basic research to healthcare systems.
 |
| Microchip technology makes many processes faster and more efficient |
Microchip technology
Microchip technology made many processes more efficient and faster and allowed
them to take place at lower temperatures, said Dr DEREK CRASTON (Laboratory
of the Government Chemist).
A measure of the progress that had been made over the past few years was the
increased speed of capillary zone electrophoresis separations, which, in 1994,
had taken 24 seconds but which could now be accomplished in microseconds.
The technology had grown out of the microelectronics industry and mainly used
2 to 3in silica wafers. Topographical features were produced on the wafers by
a variety of lithographic processes, which either dug into the surface of the
wafer or added layers on to the substrate.
Using a variety of etching agents, it was possible to produce channels with
different cross sections. Some applications included microfluidics, analytical
separations and gene (DNA) arrays, as well as microreactions.
Dr Craston highlighted some future advances, such as the modelling of new designs
of chip, the implementation of new materials, such as silicon glasses, polymers
and ceramics, as well as new techniques that included laser ablation, micromoulding
and embossing. Achieving the ultimate goal of a separation and detector system
on a chip — a “lab on a chip” — might not be far off, although
its wider application awaited broader commercialisation, he said.
Single cell assays
Professor JON COOPER of Glasgow university also emphasised speed in his talk
on single cell assays.
Single cells were commensurate with microsystems, with volumes of 1pL/cell and
dimensions of 5 to 100µm. Using single cells, it was possible to screen
a large number of drug candidates for their potential efficacy using chemical
markers. For example, in heart cells, it was possible to measure adenosine,
lactate and calcium efflux. Using brown fat cell clusters of up to 15 cells,
it was possible to monitor heat output using microcalorimetry.
Single cell assays provided economies of scale, with low material costs and
high throughput. As always, there were limitations. Cell survival was limited
to two or three hours and the inevitable biological variability necessitated
multiple measurements in order to obtain definitive results. Nevertheless, the
technology provided a means of screening many drug candidates rapidly.
A laboratory on a chip
Dr COULTON LEGGE (research and development, Glaxo Wellcome) provided an overview
of the application of microtechnology.
He covered topics ranging from microchemical synthesis, drug candidate screening,
analysis, drug delivery microsystems and diagnostics.
At the chip level, new chemistry applied. Laminar flows could result in new
separating systems, although fouling from “rubbish” and bubbles did
complicate the process. In addition, increased thermal transfer efficiencies
meant that many reactions could now take place at room temperature.
Analytical systems still awaited the integration of all activities, including
sample introduction, preparation, separation and quantitation. However the potential
increase in productivity was immense — not only were assay times measured
in microseconds but the possible number of parallel arrays was almost limitless.
In addition, reduced solvent use minimised health and disposal hazards, while
the simplicity of the system improved the robustness of assays.
In terms of drug delivery, new microtechnology was involved in systems such
as inhalers, painless injections, patches, “intelligent” pills and
electroporation. The diagnostic field was dominated by DNA arrays capable of
determining genetic predisposition to disease.
In general, microchip technology was not cheap, hence there had to be a distinct
advantage to warrant its use. As the applications and demand increased it was
likely that costs would decrease. However, this was unlikely until commercialisation
of the processes accelerated.
Synthesis and analysis
Expanding on the synthetic aspects, Dr MICHAEL MITCHELL (Imperial College, University
of London) talked about a microchip-based synthesis and total analysis system
and its role in online production and analysis of libraries of compounds.
Online synthesis eliminated the need for solid supports used in reactions, as
well as the need to remove the product from the support. This would be an advantage
as these supports could influence the chemistry of reactions.
Chip technology made it possible to carry out online purification and analysis.
Using a multicomponent reaction system with 16 channels, it was possible to
carry out real-time analysis, with the chip linked to a time-of-flight mass
spectrometer.
High surface areas and high thermal transfer eliminated the need for heat and,
by changing the dynamics, it was possible to see transient intermediates and
evaluate mechanisms. Thus, although a conventional detection system was used,
chip technology could accelerate the synthetic and analytical processes.
Diagnostic testing
The main topic covered by Mr JAMES JACKSON (Smartsensor Telemed Ltd) was how
chip technology could be used to benefit patients.
He illustrated how patients in their own homes, using a drop of blood, could
screen themselves for specific genomic panels, monitor drug therapy and screen
for or monitor specific disease states (eg, prostatic cancer using prostate-specific
antigen as an indicator).
The whole system could be housed in a credit card-sized chip and the results
could be transmitted to a “break off” chip. This could be mailed to
a central data processor, taken to a pharmacy or downloaded via a modem.
Mr Jackson suggested that enzyme-linked immunosorbent assay (ELISA)-based chips
could be available in the next two to three years, while genomic panels would
take five to 10 years to reach the home diagnostic stage.
With an ageing population that required increased levels of health care, it
was essential to maximise the use of available resources. Implementation of
this technology provided one possible means of achieving this.