The goal: rapid, precise testing for prostate cancer diagnosis

During diagnosis and care of prostate cancer, PSA concentration (prostate-specific antigen) is determined at all stages: early recognition, exploratory investigation, treatment monitoring and follow-up care. Even a few nanograms PSA per millilitre blood (ng/ml) are an indication of whether and which further tests and treatment are needed. Higher PSA concentrations may be a sign of cancer or its return. The physician takes blood and sends it away for analysis. The PSA test results usually take a few days to come back. Not only for PSA concentrations, science has been working on one new point-of-care (PoC) testing system after another which may obviate costly, time-consuming lab tests carried out on huge, complex apparatus and reduce to a minimum the usually very worrying wait for the patient.

In many cases, such solutions involve test strips which change colour enabling the doctor to assess concentrations in the consultation room. The colour changes vary in intensity and are caused by biochemical reaction. There has been a move in recent years towards using PoC devices with photodetectors or a camera for concentration testing.

Apparatus of this kind still labours under the disadvantage of inaccuracy in comparison with laboratory testing. In the case of PSA detection, the ”Rili-BÄK“ (the guidelines published by the German Medical Association (Bundesärztekammer) for quality assurance in medical laboratory tests) prescribe a lower detection limit of 0.2 ng/ml and a range up to 50 ng/ml. Confidence in the results depends on a coefficient of variation (CV) which is at most 15.5%. Measurements taken with a PoC reader and PSA test strip combination developed for reference purposes in the current research project, however, failed to reach these standards. 

Chip-based prototype detects and measures PSA at less than one nanogram per millilitre

In the INSPECT project, IMMS designed and developed a photometer as a portable reader in combination with a replaceable opto-electronic CMOS biochip and produced a demonstration model. Instead of the test strip employed to date in certain PoC systems with camera, the new version measures the biochemical reaction without a gap between photometer and sample, which is placed directly onto a microelectronic chip. IMMS’ partner in the project, the company Senova Gesellschaft für Biowissenschaft und Technik mbH, undertook the tasks firstly of providing the chip surface with its biochemical functions using immobilised prostate-specific antibodies and secondly of using the prototype to measure samples with various PSA concentration levels. If the sample contains PSA, this is shown by biochemical reactions which darken the sample to an extent that varies with the concentration and with photometry and electronics the differences in brightness are measured. It is a world first for the Senova and IMMS partnership that the presence of PSA on a CMOS biochip can be proven with a lower detection limit of 0.1 ng/ml. This degree of accuracy fulfils the requirements for clinical PSA tests set by ”Rili-BÄK“. The total time required for the test with the CMOS biochip is 14 minutes, there is digital output of the results and these can be processed on a computer connected to the diagnostic device.

For the test and characterisation of the developed integrated circuits, we used and further developed our modular and mobile test systems.