IMMS: Microelectronics measures antigen concentration
IMMS will present a mobile microelectronic testing system for early diagnosis of prostate and colon cancer. Via live-demo of a functional model IMMS will illustrate the detection principle the current work is based on and which is carried out in the INSPECT project with four partners in Thüringen, Germany. It is the role of IMMS to develop the application-specific microelectronics, focussing on signal processing, particularly in the case of very weak signals, and efficient noise suppression for these. These chips are currently being used by the Senova Gesellschaft für Biowissenschaft und Technik mbH to conduct extensive test series with biological samples. The foundation is Senova’s expertise in immunological assays and in biochemical surface functionalisation of chips. Thanks to the combination of immunological testing methods with microelectronics it becomes possible to early, precisely and reliably verify lowest concentrations of cancer biomarkers.
Present rapid tests no more than qualitative
There are certain types of cancer for which the patient’s doctor can test rapidly on the spot, obtaining an immediate result and saving costly, time-consuming lab tests. The present state of the art includes the strip test on which antibody molecules have been deposited. These seeker molecules have a colour marker and will bind the target molecule to them, producing a result within 5 or 10 minutes: the answer is "yes" or "no" according to the presence of a coloured line. However, varying strength in the colour of this line is not information that the user can interpret. It is also possible for a very pale line to be overlooked.
Future quantitative rapid tests for exact diagnosis
On the other hand, if it were possible to measure the exact concentration of certain molecules in sample fluids, reliable diagnosis could be achieved. Particularly in the case of cancer of the prostate, there would be a great improvement if the on-site diagnostics could include such quantitative analysis. Although the presence of PSA (prostate-specific antigen) may be an indicator of cancer, it is constantly being produced in the male body. A man less than 50 years old will have a PSA concentration of less than 2.5 ng/ml (the unit is in thousand-millionths of a gram, i.e. in nanograms, per millilitre). At over 70, a man will have a level around 6.5 ng/ml. It is possible for these values to vary independently of age; the cause may be inflammation, mechanical irritation or cancer. If there is a carcinoma developing, the patient’s PSA concentration will be rising continuously. If the PSA concentration could be measured at regular intervals, reliable early diagnosis and early treatment would result.
Microelectronics to measure antigen concentrations in colon and prostate cancer
The biotechnical principles on which the new test system will be based are comparable with those for the strip test. The interaction between antibody and antigen is intended to enable detection of analytes in a sample: PSA in the case of prostate cancer and haemoglobin in the case of colon cancer. To meet the diagnostic needs, the chip must be capable of recognising concentrations of antigens in the range of one nanogram per cubic centimetre. These low concentrations induce very weak fluctuations in the luminous intensity, between 0.01 Bel and 1 Bel.
IMMS has thoroughly investigated the technical feasibility of achieving this level of accuracy for the purpose of cancer diagnosis. As a first step an already available chip originally intended for detecting infectious diseases was evaluated to see how it would visualise varying levels of brightness in sample fluids where the concentration of particles is known. TMB (tetramethylbenzidine) substrate solutions were deposited on this chip and the TMBs were enriched with HRP (the horseradish peroxidase enzyme). The chemical reactions which took place turned the fluids blue – the lower the concentration, the more slowly. The chips were used to measure the gradual attenuation of light due to staining over time and tiniest HRP quantities have already been verified.
For this purpose, 4 sample solutions were used which contained 0 ng/ml, 0.2 ng/ml, 1 ng/ml and 5 ng/ml of HRP respectively. For each sample, on addition of the specified HRP concentration, a brightness value was recorded for each second over a period of 600 seconds. These recordings proved that the alterations in brightness were indeed in the range 0.01 Bel to 1 Bel and the visualised differences in the reaction processes were consonant with expectations. It is intended to rely on this preparatory work in developing correlations for the analyte concentrations which would prove the presence of PSA and haemoglobin to specify requirements for the new chip design.
View on the intermediate state of the mobile microelectronic-based test system
"A point-of-care diagnostic system could be prototyped, allowing bio-medical analyses to be carried out at the premises of the Senova GmbH. The high resolution of the signals and the accurate signal detection made it clear that simple, quick, reliable diagnosis and monitoring of certain cancers is possible," says Dr. Friedrich Scholz, Senova Gesellschaft für Biowissenschaft und Technik mbH, about the state of development. "The system is currently being tested for prostate and colon cancer diagnostics. In the future the various sensors on the chip should allow the analysis of a range of parameters so that cancer diagnosis will become ever more reliable and certain and so that the monitoring of individual therapies will become possible."
The INSPECT project was funded by the "Land" of Thüringen and the European Union under the reference 2015 FE 9159.
- CDA GmbH (www.cda.de)
- iba Institut für Bioprozess- und Analysenmesstechnik e.V. (www.iba-heiligenstadt.de)
- IMMS Institut für Mikroelektronik- und Mechatronik-Systeme gemeinnützige GmbH (www.imms.de)
- Senova Gesellschaft für Biowissenschaft und Technik mbH (www.senova.de)
- X-FAB Semiconductor Foundries AG (www.xfab.com)
About Senova Gesellschaft für Biowissenschaft und Technik mbH
Senova is an internationally active medium-sized and owner-managed company based in Weimar. Senova is specialized in high-quality immunological rapid tests for the detection of proteins, haptens, nucleic acids, microorganisms and viruses. With its powerful research department, extensive methods for quality assurance and quality management and large production capacity for test kits Senova provides its customers with all the tools available to develop, validate, and produce rapid test products successfully. This product and service portfolio is complemented by a well-developed distribution network in human and veterinary diagnostics by our partner Devidia - Deutsche Vitaldiagnostik.
Senova rapid tests for point-of-care diagnostic are based on the well-established lateral flow technology or innovative 3D immunofiltration. Senova develops new test systems or establishes new tests on existing platforms on behalf of its clients. The team can take advantage of a wide range of tools and methods which have emerged in recent years through intensive technology development and cooperation with research partners.
The company is certified ISO 13 485 and ISO 9001 since 2011 and features a fully certified quality management system.
IMMS serves small and medium-sized industrial enterprises through preliminary research. It acts as their strategic partner in the development of micro-electronic and mechatronic products and of systems technology.
This entails devising extremely precise and energy-efficient comprehensive solutions for the fields of automation, semi-conductors, medical technology, life sciences, and environmental or automotive engineering. A further role of IMMS is to contribute research to the technology of a range of industrial techniques: communications, measuring and control technologies and micro-/nano-engineering.
For its partners, IMMS is the cutting edge , slicing through the barriers between science and manufacturing, so that in many cases its partners will be five or ten years ahead of the competition. IMMS is thus a veritable bridge between science and industry.
The IMMS motto, "Wir verbinden die IT mit der realen Welt", emphasizes the need and the challenges inherent in connecting IT to the real world. Consequently, the Institute concerns itself with designing and creating sensor and actuator systems, control and feedback systems, and signal processing systems, then also integrating the systems and linking them to their environment. The work is to develop and optimize all the individual system elements, components and circuits and to achieve communication not only between those elements but between them and their environment.
Currently, there are 80 staff members working at this Institute, which was founded in 1995 as an associated research institute of the TU.