Researchers from Helmholtz Munich and the Technical University of Munich have developed a novel method to track cancer treatment responses in individual cells – without the need for dyes or labels. Their mid-infrared optoacoustic microscopy (MiROM) technology enables real-time visualization of protein changes inside living myeloma cells, providing early insights into treatment effectiveness. By detecting protein misfolding, a key indicator of myeloma treatment response, MiROM offers a faster, more precise approach to personalizing therapy for multiple myeloma patients.
Spotting the Missteps: How MiROM Detects Protein Misfolding in Cancer Cells
MiROM identifies proteins by using mid-infrared light to detect molecular vibrations – essentially the natural “dance” of molecules within protein structures. Unlike optical spectroscopy, which measures light attenuation, optoacoustics capture ultrasound waves generated when proteins absorb infrared light. This absorption causes a tiny, localized temperature increase, leading to transient expansion of medium surrounding the protein and the emission of ultrasound waves. By analyzing these signals in real time, MiROM can detect structural changes in proteins, such as misfolding, by recognizing shifts in their molecular “dance”. This capability provides crucial insights into how cancer cells respond to treatment.
Overcoming Limitations in Myeloma Therapy Assessment
Multiple myeloma is a blood cancer that affects plasma cells in the bone marrow, leading to abnormal protein production, weakened immunity, and organ damage. Traditional methods for evaluating myeloma treatment often require large cell samples, complex preparation, and time-intensive measurements, making it challenging to monitor individual patient responses in a timely manner.
MiROM overcomes these limitations by analyzing single cells, requiring only a minimal number of patient samples, and providing fast, nearly real-time assessments of treatment effectiveness.
“Since MiROM can analyze individual cells in real time without the need for elaborate sample preparation, it offers fast insights into how treatments may impact protein structures at a cellular level,” says Francesca Gasparin, first author of the study. “Specifically, MiROM detects the formation of intermolecular beta-sheets (structures linked to protein misfolding) as well as apoptosis, the programmed cell death that indicates whether cancer treatments are working or if drug resistance is developing,” add Prof. Miguel Pleitez and Prof. Florian Basserman, senior investigators in the study.
By analyzing individual cells, MiROM can uncover variations in treatment response within a patient’s cancer, paving the way for personalized therapy adjustments.
One Tool, Many Applications
Beyond multiple myeloma, MiROM holds great potential for other diseases linked to protein misfolding, including Alzheimer’s and Parkinson’s. Ongoing advancements – including optimizing laser pulse duration and increasing imaging speed – could further enhance its sensitivity and broaden its clinical applications.
“We envision the use of MiROM in drug screening, diagnostic tests and home-based patient monitoring,” says Prof. Vasilis Ntziachristos, also a senior investigator in the study. Future clinical validation in larger patient cohorts will be the next step toward bringing this technology into routine medical practice.
About the Researchers
Prof. Vasilis Ntziachristos, Head of the Bioengineering Center and the Institute of Biological and Medical Imaging at Helmholtz Munich. He also holds the Chair of Biological Imaging at the Technical University of Munich (TUM) and is a founding member and in the Board of Directors of TranslaTUM, TUM's Central Institute for Translational Cancer Research. At TranslaTUM, researchers from medicine, engineering, and natural sciences collaborate to rapidly translate cancer research discoveries into clinical applications.
Francesca Gasparin, Researcher at the Institute of Biological and Medical Imaging at Helmholtz Munich and the Chair of Biological Imaging at the Technical University of Munich (TUM).
Prof. Miguel A. Pleitez, Group Leader for Translational Optoacoustics at the Institute of Biological and Medical Imaging at Helmholtz Munich, Chair of Biological Imaging at the Technical University of Munich (TUM), Group leader at TranslaTUM.
Prof. Florian Bassermann, Director of the Department of Medicine III (Hematology/Oncology), TUM University Hospital, Technical University of Munich (TUM), Group leader at TranslaTUM.
About Helmholtz Munich
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has around 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en
Prof. Vasilis Ntziachristos
E-Mail: vasilis.ntziachristos@helmholtz-munich.de
Gasparin et al., 2025: Label-free protein-structure-sensitive live-cell microscopy for patient-specific assessment of myeloma therapy. Nature Biomedical Engineering. DOI: 10.1038/s41551-025-01443-3
https://www.nature.com/articles/s41551-025-01443-3
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