FluoResYst

Press Release: official Kick-off of the BMBF Project FluoResYst

Rapid Multiresistence detection system for Tuberculosis infections: eight partners from Research and Industry start the BMBF-funded FluoResyst Project

Ending the tuberculosis epidemic by 2030 is one of the goals of the United Nations. In 2020, approximately 10 million infection cases were recorded worldwide, with around 1.5 million individuals succumbing to the disease. This places tuberculosis as the second deadliest infectious disease globally, following COVID-19. Multidrug-resistant variants of Mycobacterium tuberculosis pose an increasing challenge in the diagnosis and successful treatment of the disease, primarily due to limited laboratory infrastructure in developing countries. A national consortium comprising eight companies and non-academic research institutions aims to address this issue with the assistance of photonics and presented their solutions at the kickoff meeting of the three-year BMBF-funded project FluoResYst on January 13th, 2022. The project’s objective is to develop a compact detection system for multidrug resistance in tuberculosis infections, enabling rapid diagnosis and effective treatment of affected individuals.

Photonics Point-of-Care Detection System Instead of Laboratory Diagnosis
To combat multidrug resistance in tuberculosis bacteria, suspected cases must be tested daily, and, in the event of a positive laboratory result, treated and isolated promptly. However, the necessary laboratory infrastructure and logistics are often lacking, as 95% of tuberculosis cases occur in developing and emerging countries. In the project “Time-Resolved Fluorescence Detection for Integrated Multiparameter Analysis of Multidrug Resistance, Exemplified by Tuberculosis,” abbreviated as FluoResYst, the partners will develop an innovative method for accelerated diagnostics of multidrug resistance in bacterial pathogens, using tuberculosis as an example. The goal is to create a compact and cost-effective photonics point-of-care detection system that allows tuberculosis diagnostics outside of laboratories, enabling rapid on-site testing.

Innovation: Combining Fast Fluorescence Effects with Rapid Detectors
The innovative method aims to shorten manual laboratory steps for biochemical detection, making them readily available within the device. It also achieves rapid detection and analysis through integrated optoelectronic components. Detection of the resistance genes of the pathogens is based on a fluorescence quenching effect, where the fluorescence of a dye attached to a DNA fragment is suppressed by antibody binding. When a sample contains the target gene segment, the antibody is released, and the DNA fluoresces.
To capture fluorescence, the relevant dye molecules are excited with light at a specific wavelength, which then emits light at another wavelength for measurement. To make the detection system cost-effective, it distinguishes excitation and fluorescence light not through expensive optical filters but through their decay times. The fluorescence dyes used for the quenching effect have very short nanosecond-scale decay times. To measure the multidrug resistance genes with time resolution, a very fast image sensor and an even faster laser for excitation light, switching on a picosecond scale, are required. New integrated circuits are being developed for both components as part of the project. The image sensor uses new single-photon avalanche diodes (SPAD). These highly sensitive photodiodes, mostly used in autonomous driving applications, can not only detect single photons but also achieve the required measurement speeds up to the gigahertz range.
Platform Adaptable for Other Multidrug Resistance Detection

The combination of these two innovations, the biochemical fluorescence quenching antibody assay with the photonics integration of time-resolved fluorescence measurement for short-lived fluorochromes, results in a new detection technology that significantly simplifies complex analyses, making them widely available. The development of this platform will not only enhance tuberculosis diagnostics and multidrug resistance determination but will also contribute to curbing the disease through accelerated on-site diagnostics. Its adaptability for other multidrug resistance detection will also optimize the diagnosis of other resistance-prone infections.
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Consortium partners include LIONEX GmbH (Consortium Coordinator), IMMS Institute for Microelectronics and Mechatronic Systems GmbH (IMMS GmbH), iC-Haus GmbH, X-FAB, DITABIS Digital Biomedical Imaging Systems AG, Fraunhofer Institute for Cell Therapy and Immunology, Bioanalytics & Bioprocesses Division (IZI-BB), microfluidic ChipShop GmbH, and the Institute for Molecular Diagnostics and Bioanalytics (IMDB) gGmbH.

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