Klaus Gerwert and Grischa Gerwert in a betaSENSE laboratory
Photo Credit: © Dennis Yenmez/Stadt Bochum
Scientific Frontline: Extended "At a Glance" Summary: Immuno-Infrared Sensor for Neurodegenerative Disease Detection
The Core Concept: A novel blood test utilizing an immuno-infrared sensor platform to detect the earliest biological signs of Alzheimer’s and Parkinson’s diseases prior to the onset of clinical symptoms.
Key Distinction/Mechanism: Unlike conventional symptom-oriented diagnostics, this technology uses specific antibodies immobilized on a sensor to isolate misfolded protein biomarkers—amyloid beta (Aβ) for Alzheimer’s and alpha-synuclein (α-Syn) for Parkinson’s—directly from complex body fluids. The degree of protein misfolding is then accurately quantified using highly sensitive quantum cascade laser technology combined with infrared spectroscopy.
Major Frameworks/Components:
- Biomarker Isolation: The strategic use of specific antibodies to capture targeted neurodegenerative proteins directly from blood samples.
- Quantum Cascade Laser Technology: Advanced infrared spectroscopy that sensitively detects secondary-structure-specific changes and misfolding in target proteins.
- Patented Surface Chemistry: A specialized sensor coating that successfully immobilizes antibodies, paired with a blocking layer that prevents non-specific binding from background fluids.
- Difference Spectroscopy: A computational and optical method to extract the targeted biomarker's precise spectrum from the complex background noise of the body fluid.
Branch of Science: Biophysics, Molecular Biology, Laser Spectroscopy, and Neurology.
Future Application: The technology's high scalability allows for parallel measurements, laying the groundwork for cost-effective, population-wide early screening. Additionally, it is currently utilized in clinical studies by the contract research company BetaSENSE to evaluate the efficacy of new pharmaceutical treatments, such as vaccines against Parkinson's disease.
Why It Matters: Irreversible brain damage occurs long before the clinical symptoms of Alzheimer's and Parkinson's appear. Because effective medications now exist, early detection is essential for successful therapeutic intervention. This non-invasive method allows treatments to begin proactively, addressing an unmet medical need and alleviating the growing strain on global healthcare systems.
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| Misfolding of α-synuclein (α-syn) deposited in Lewy bodies in the brain is a hallmark of Parkinson’s disease. Such misfolded α-syn is also observed in blood and therefore allows a biological classification of Parkinson’s, an unmet medical need. The immuno-infrared sensor (iRS) measures the degree of α-syn misfolding and thereby addresses this need by a non-invasive and cost-effective blood test. Image Credit: © Hartmann/betaSENSE | Cover Image |
An early start to treatment is crucial to successful therapy. A new sensor is helping with early detection.
For the first time, therapeutically effective medications are now available for Alzheimer’s disease. Effective symptomatic therapies also exist for Parkinson’s disease. However, a prerequisite for successful treatment is early diagnosis—ideally through a simple blood test conducted as part of a preventive screening, even before clinical symptoms appear. A research team led by Professor Klaus Gerwert from Ruhr University Bochum, Germany, has developed just such a blood test. It is based on the immuno-infrared sensor, a novel platform technology to which the Journal of Physical Chemistry B dedicates its cover story.
In our aging society, cases of Alzheimer’s and Parkinson’s disease are rising dramatically. This is not only immensely challenging for patients and their families, but it is also putting increasing strain on our health care systems.
Modern diagnoses are largely symptom-oriented and thus are usually made too late. The brain is already massively and irreversibly damaged by the time symptoms start to appear. “Because of this, there is a broad consensus in the scientific community that therapy needs to begin much sooner,” says Klaus Gerwert, “even before the typical insoluble protein deposits form in the brain—these being amyloid plaques in the case of Alzheimer’s or Lewy bodies in Parkinson’s.”
Analyzing Biomarkers in Complex Body Fluids
The sensor method developed by the research group is based on the concept of using specific antibodies to isolate misfolded biomarkers directly from body fluids—the amyloid beta protein (Aβ) for Alzheimer’s and alpha-synuclein (α-Syn) for Parkinson’s. The degree to which these biomarkers are misfolded is a very early indicator of neurodegenerative processes. This misfolding is detected utilizing modern infrared spectroscopy and highly sensitive quantum cascade laser technology.
A newly developed and patented surface chemistry is used to immobilize the antibodies on the sensor, while a specially developed blocking layer prevents nonspecific binding to the surface. This enables the secondary-structure-specific infrared spectrum of the biomarker to be directly isolated from the complex body fluid background spectrum using difference spectroscopy.
“These unique measurements are possible because of the combination of molecular biology, biophysics, and laser spectroscopy,” says lead author Dr. Grischa Gerwert. Furthermore, this interdisciplinary technology possesses broad application potential for the analysis of a wide variety of biomolecules in complex solutions.
“One special advantage of quantum cascade laser technology lies in its high scalability through parallel measurements,” Grischa Gerwert adds. “Consequently, this method holds promise for broad clinical application and population-wide screening in the future.”
Working Intensively to Obtain Approval
The immuno-infrared sensor is already being used in clinical studies by Gerwert’s company, BetaSENSE. This company evaluates new medications on behalf of the pharmaceutical industry, including a vaccine against Parkinson's disease, as part of contract research.
Approval according to the European In Vitro Diagnostic Medical Devices Regulation (IVDR) is required for the blood test to be available as an early detection test for the general public. This entails considerable regulatory effort and financial expense. “At BetaSENSE, we are working hard to advance the approval process and make the test available to the public as soon as possible,” says Grischa Gerwert.
Funding: The work was funded by the North Rhine-Westphalia Ministry of Culture and Science within the framework of the Center for Protein Diagnostics (PRODI).
Published in journal: Physical Chemistry B
Authors: Grischa Gerwert, Marvin Mann, Lennart Langenhoff, Nathalie Woitzik, Diana Hubert, Deniz Duman, Adrian Höveler, Sandy Budde, Jonas Simon, Léon Beyer, Martin Schuler, Sandrina Weber, Brit Mollenhauer, Carsten Kötting, Jörn Güldenhaupt, and Klaus Gerwert
Source/Credit: Ruhr-Universität Bochum
Edited by: Scientific Frontline
Reference Number: biph052126_01