3 â€“ 7 June 2002, Munich, Germany
More than two dozen international biochip conferences have been announced for this year to be held in United States and Europe. Most of them have a commercial background, so as the EuroBiochips 2001, held from 6-8th of June in Munich, organized by IBC Global Conferences Ltd., London. Obviously, in this field enough new scientific results are produced and new technologies being developed to attract an auditorium, able to afford the fee of about 3.000 DM for a three-day conference, or the number of people who are willing to enter this field is still high enough to fill these auditoria. The EuroBiochips 2001 meeting at least was one of the few fulfilling both of these expectations. It showed, that the interest in and the demand on this technology have not yet declined and that there are still huge scientific and commercial hopes in this field.
The conference has clearly been dedicated to the technical development and only a few lectures included detailed biological results obtained with microarrays or similar technical solutions. The conference was divided in the following topics: Applications in drug discovery, bioinfor-matics and data analysis, business of biochips, diagnostics, emerging technologies, micro-fluidic technologies and protein arrays. The more than 300 participants enjoyed about 40 lectures and 16 posters, most of them scientifically and technically at the top level. A few new methods, like the scanometric approach of using gold nanoparticles enhanced by silver reduction for hybridisation detection and the mask less synthesis of oligonucleotides on the chip have not been presented. But nevertheless, the conference gave an almost comprehensive overview of all aspects of the microarray technology including microfluidics and bioinfor-matics. An extra bonus was the accompanying exhibition, in which 28 companies demon-strated their arrayers, microarray-chips and related lab ware, scanners, software tools, services and other new developments.
Although construction, properties and application of these microarray components have been the general theme of this meeting, the focus of attention at this conference was clearly the progress in microfluidics. One of the most convincingly demonstrated advances in this field was the new laced concept, which seems now to bring truly in reality was often and too early has been announced as lab-on-the chip technology.
In this respect, the lectures of S. Oâ€™Connor (Nanostream Inc.) and B. Carvalho (Tecan) as well as from O. Larsson (Amic AB) and R. EhrnstrĂ¶m (Gyros AB) were of special interest. They demonstrated, that almost all important lab techniques, like pumping, valving, passive and active fluid distribution, metering, mixing, solid phase binding, washing, elution, filtration, cell growth and lyses, centrifugation, separation, heating and different methods of signal detection can be carried out in 96 or more parallel units integrated into one single laced. This astonishing versatility and accuracy is achieved by specially designing the diameters, length, geometry, angles, density and material surfaces of the micro channel structures in relation to the viscosity, the surface tension and other properties of the fluidic solutions to be processed during the analytic run, in which the driving forces are easily controlled by varying acceleration and velocity of the labCD. The execution of 48 enzyme inhibition reactions in a total volume of 12 Âµl using fibber optic detection, and multiplex PCR as well as online PCR reactions including the lyses of E. coli cells have been realized. â€śFit the chip to the assay not vice versa!â€ť was a statement in this context, underlining the technical progress recently made in material sciences and fabrication technology to produce micro channels and microstructures for special functions. Examples are micro chambers for perfect mixing microfluidic streams and pressure dependent valves, opening e.g. only around 5 psi and closing at lower as well as at higher pressure, simply controlled by the speed of the labCD. More than 40 different polymers, including Teflon, are presently in use for producing special surface qualities and 400 more are expected to be available in the next years to come. Using this technical opportunities, about 100 chromatographic systems have been realized on one single labCD prototype. Applications are seen for high throughput drug discovery, genomics, proteomics, clinical and molecular diagnostics as well as the analytical routine in food and feed industry and other fields.
This type of system obviously has the potential to become the platform of choice for the true lab-on-the-chip and to be introduced quickly into the clinical routine, because most of the bio-chemistry and lab techniques presently in use in clinical analytics can directly be integrated into this technology. The only technique presented at the EuroBiochips 2001, competitive with this kind of approach, was the so-called eSensor platform from Clinical Micro Sensors and Motorola. Tim Tiemann described in his lecture â€śDNA-diagnostics â€“ mass applied geno-micsâ€ť, that the eSensor 4800 system contains biochip cartridges producing an electronic readout without the need of washing steps based on hybridisation reporter molecules. The desktop or handheld versions of these devices allow analysing 36 post amplification samples of any DNA or RNA targets per chip and are simple and flexible to use by non-skilled users, because they work without any optical or fluidic elements. At the moment there are panels for pathogens, SNPâ€™s and genetic diseases available. For introducing this technology successfully to the clinical routine laboratory the only scientifically relevant points are sensitivity and specificity, whereas the following factors were designated as the most important ones: costs for establishing the technique in the lab and cost per test panel, the ease of using the system, the time needed per test, regulatory issues and intellectual property rights.
This level of applicability in â€śreal lifeâ€ť situations outside the research laboratory has not yet been reached by any other commercial system based on microarray technology, although D. Hall (Agilent) reported about a highly integrated program for preparing the first â€śpreplot-human1-arrayâ€ť (on two slides), based on inkjet-technology for producing the chips, a special hybridisation chamber, a â€žsecond generationâ€ś scanner including a 48 slide carousel and a high performance software Therefore D. Blohm (University of Bremen) might be right to empha-size, that the microarray technology is at present still exclusively a research method, because itâ€™s five separate modules, the chip, the arrayer, the hybridisation station, the scanner and the software tools are too complex to be integrated into a robust, automatable and easy to use stand alone equipment. Such a gene sensor device is being developed as a flow-through system based on re-usable chips and with a label free readout for nucleic acids as well as for proteins and other biomolecules. It is expected to have the additional advantage of enabling the measurement of binding kinetics in each individual spot of a microarray, even under vary-ing experimental conditions.
Although there were no reports about the influence of the chip-quality and other steps of the complex experimental procedure on the final hybridisation results, the issue of data quality played a less important role during this conference as compared with other recent meetings in this field. However M. Iyer (Corning) announced at this congress an astonishing efficient new chip producing process, which allows spotting 10.000 different oligonucleotides on a slide in about six seconds. May be this kind of technological breakthrough is helping to bring down the prices of microarrays and to expand their application and to speed up the definition of technical standards for this technology. An other non-contact, high efficient microarray pro-duction strategy has been developed and presented by HSG-IMIT (Villingen/Schwenningen) as the so-called topspot system, which is able to spot more than 1.000 oligonucleotids in about ten seconds.
Strong efforts are being made to transfer the knowledge accumulated for DNA microarrays into the field of proteomics. M. Pawlak (Zeptosens) presented e.g. a well characterized pro-totypic system, composed of microarrays with 3.066 spots/cmÂ˛, a special reader with a linear dynamic range of 3,5 decades and a proprietary software. Based on the evanescent fluores-cence method this device has a detection limit of about 500 zeptomole and works with 1-10 pg/ml protein in a serum sample of 15 Âµl without the need of special purification steps.
The next technological step, to produce tissue microarrays for analysing e.g. the pathology of cells, tissues and organs, as illustrated by O. Kallioniemi (NIH) at this conference, gave an imagination of the potential for future developments, because traditional methods allow to analyse a molecular marker in one given tumour, but with microarrays it is possible to analyse a whole spectrum of molecular markers in tumours at the population level.
The patent situation is in all fields of this technology still a matter of controversy, in the area of nucleic acid as well as in proteomics and other types of arrays, because the final outcome of the opposition and litigation proceedings about the basic microarray patents, corresponding to the EP 619 321, owned by Affymetrix, and EP 373 201, owned by Oxford Gene Technolo-gy, is not yet foreseeable. Therefore D. TrĂ¶sch (Reinhardt SĂ¶llner Ganahl) clearly explained, that everyone who is involved in the microarray business is highly recommended to monitor closely the patent situation and the corresponding proceedings.
As a concluding message, the current trends in the field of microarray technology presented at the EuroBiochips 2001 conference, can be summarised as follows: Ten years after itâ€™s first steps of development the microarray methodology has not yet left the research laboratory but is now moving quickly towards real-life applications. In connection with the rapid progress in microfluidic techniques and technical breakthroughs concerning the production of low cost but high quality chips as well as further miniaturisation and higher degrees of multiplexing a huge potential of further technical developments can be expected.
Simone Weyand and Dietmar Blohm
University of Bremen, FB2-UFT
Department of Biotechnology and Molecular Genetics
Leobener StraĂźe, D-28359 Bremen
Tel. +49 (0) 421-218-4780
Fax. +49 (0) 421-218-7578
The Microarray and Microfluidic Technology Congress, 3 â€“ 7 June 2002, Munich, Germany