Patent DE 10 2024 138 869

High-precision medical diagnostic systems are large and expensive, they are primarily used in centralised laboratories and involve waiting times and travel times of several days. However, where rapid test results are essential or investment in a laboratory is not feasible, as, for example, in countries of the Global South, point-of-care (PoC) tests are an option. To this end, the IMMS is developing CMOS-based biosensors that enable structural dimensions in the µm range to be realised, thereby allowing properties to be measured at the molecular scale. A novel SPAD-based sensor for the time-resolved readout of fluorescence-labelled DNA microarrays contributes to more precise PoC measurements.

In the field of medical diagnostics (in vitro diagnostics), the concentration of analytes such as proteins or DNA can be determined using time-resolved fluorescence measurement. To test different analytes simultaneously, so-called microarrays with individual test spots are used. During the measurements, the microarrays are usually illuminated by a laser, which excites an added fluorescent dye to emit light depending on the concentration of an analyte. The concentration of an analyte can be determined from the ratio of excitation light to fluorescence light.

Single-photon avalanche diodes (SPADs) are suitable for measuring the fluorescence light; these allow individual photons to be detected with high temporal resolution (time-correlated single-photon counting, TCSPC). An SPAD arrangement comprising one or more SPADs corresponds to a test spot.

The excitation light is not distributed homogeneously across the entire microarray. However, the intensity of the excitation light must be known at every position on the microarray in order to enable the determination of the molar concentration of an analyte. Due to the properties of the excitation light, SPADs are not suitable for measuring it. Consequently, in the current state of the art, the excitation light is homogenised using complex and costly optical systems.

The concept behind the invention is a cost-effective solution that dispenses with homogenisation and involves placing additional photodiodes between the individual SPAD arrays in order to determine the intensity of the excitation light. Through normalisation and interpolation, the light can be calculated precisely for each test spot. This enables targeted correction of inhomogeneity, and a large number of test spots on a given microarray can be examined and analysed accurately at the same time.

Advantages of the invention 

• Elimination of complex and costly homogenisation optics
• Targeted correction of the inhomogeneity of the excitation light through its precise calculation for each test spot
• High-precision PoC measurements to determine the concentration of, for example, DNA or proteins