Label-free Bioimaging Laboratory


"We aim to develop photonic-based tools in biomedicine that will ultimately create impact in health"


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We are a multidisciplinary research team based at King's College London and Guy's Hospital dedicated to the cutting-edge field of biophotonics and its applications in the realm of health and diseases. Our work is driven by a commitment to tackle fundamental challenges in biomedicine, with the overarching goal of pioneering innovative approaches to solve clinical challenges. Follow us on twitter: @Bergholtlab

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Our Research

We innovate new biomedical imaging instrumentation and methods to study interactions between light and cells/tissue in order to address fundamental biological questions for widespread diseases, in particular for cancers. Biophotonics, the science and technology of generating, detecting, and manipulating light for biological systems, has emerged as a transformative force in biomedical research. We work at the interface of several disciplines ranging from microscopy and spectroscopy, spatial biology, advanced endoscopy and artificial intelligence. We apply advanced imaging and spectroscopic technologies including multidimensional correlative imaging to preclinical disease models and in patients to shed new light on disease onset and progression. We have fully equipped biophotonic laboratories at Guys Hospital with core label-free bioimaging facilities including multi-photon/fluorescence lifetime imaging, confocal and conventional Raman microscopy, fiber-optic Raman spectroscopy, hyperspectral imaging, DESI- mass spectrometry imaging, endoscopic/laparoscopic imaging and actively collaborate with clinicians to apply these technologies in hospitals.

The key research interests of the group fall within 3 complementary topics:

  • Multidimensional molecular imaging
  • Artifical intelligence enabled biophotonics.
  • Biophotonic applications in regenerative medicine and in vivo translation

Multidimensional molecular imaging

We innovate instrument and new technologies for multimodal bioimaging at the molecular level. In label-free bioimaging the detected light originates directly from the interaction between the excitation light and the sample. The interaction can result in a variety of physical processes, such as scattering, absorption and fluorescence decay .


The major techniques that are under development in the laboratory include correlative imaging approaches based on multi-photon, fluorescence life-time, confocal Raman spectroscopic imaging, and optical coherence tomography. We also correlate optical spectroscopy with advanced mass spectrometry including Desorption electrospray ionisation (DESI) mass spectrometry imaging (MSI) and spatial transcriptomics.


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Artifical intelligence enabled biophotonics.

Artificial intelligence (AI) has recently experienced a surge in interest and rapid advancements in various fields, including natural language processing, computer vision, reinforcement learning, and autonomous systems. Label-free bioimaging offers a powerfull analysis of biological samples such as live cells or tissues without using exogenous contrast agents.


We develop advanced Ai approaches to label-free bioimaging and biophotonics in general. This enables enhanced imaging fidelity, speeds and diagnosis


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Development of clinical biophotonics technologies for early in vivo diagnosis of diseases

Early detection and intervention of cancers are essential to decrease the mortality rate. New cost-amenable biophotonic approaches for in vivo molecular analysis could transform clinical healthcare. The next generation cancer diagnosis strategies require technologies that offers detection, grading and staging of lesions in the earliest stage of the disease.

Our approach combines optical imaging, spectroscopy and OCT to develop systems capable of comprehensive characterisation of early cancer. We believe that a multimodal imaging approach such as simultaneous Raman spectroscopy and optical coherence tomography (OCT) could become the next generation technology for in vivo diagnostics of cancers. Far-reaching implications of Raman spectroscopy are already emerging for clinical applications including in vivo diagnosis of cancers, osteoarthritis as well as monitoring of implanted tissue engineered constructs. In addition, the lab actively studies the basic mechanisms of light-tissue interactions to understand light transport in tissue.


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Publications


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Selected publications

Opto-Lipidomics of Tissues (Advanced Science).

M. Jensen, S. Liu, E. Stepula, D. Martella, A. A. Birjandi, K. Farrell-Dillon, K. L. A. Chan, M. Parsons, C. Chiappini, S. J. Chapple, G. E. Mann, T. Vercauteren, V. Abbate,and M. S. Bergholt
In this study, opto-lipidomics, a new approach to optical molecular tissue imaging is introduced. The capability of vibrational Raman spectroscopy is expanded to identify individual lipids in complex tissue matrices through correlation with desorption electrospray ionization (DESI) – mass spectrometry (MS) imaging in an integrated instrument...

Raman needle arthroscopy for in vivo molecular assessment of cartilage (Journal of Orthopaedic Research)

Kimberly R. Kroupa, Man I Wu, Juncheng Zhang, Magnus Jensen, Wei Wong, Julie B. Engiles, Thomas P. Schaer, Mark W. Grinstaff, Brian D. Snyder, Mads S. Bergholt, Michael B. Albro,
The development of treatments for osteoarthritis (OA) is burdened by the lack of standardized biomarkers of cartilage health that can be applied in clinical trials. We present anovel arthroscopic Raman probe that can “optically biopsy” cartilage and quantify key extracellular matrix (ECM) biomarkers for determining cartilage composition, structure, and material properties in health and disease....

High-Throughput Molecular Imaging via Deep-Learning-Enabled Raman Spectroscopy (Analytical Chemistry)

C. C. Horgan, M. Jensen, A. Nagelkerke, J.P. St-Pierre, T. Vercauteren, M. M. Stevens, and Mads S. Bergholt,
Here, we present a comprehensive framework for higher-throughput molecular imaging via deep-learning-enabled Raman spectroscopy, termed DeepeR, trained on a large data set of hyperspectral Raman images, with over 1.5 million spectra (400 h of acquisition) in total....

Fiber-optic probe Manufacturing Facility (FMF)

Our state-of-the-art Fiber-Optic Probe Manufacturing Facility (FMF) is our new initiative to develop fiber-optic applications in biomedicine. Within FMF, we have a wide selection of equipment for prototyping to design and engineer complex probes tailored to various applications, including Raman spectroscopy, fluorescence analysis, optical coherence tomography (OCT), multiphoton imaging and more. Reach out to us if you are interested in collaboration or use of the equipment.

  • FMF is equipped with advanced fiber cutting and splicing machines: Angle fiber cleaver , fiber cleaver fiber , stripper, fiber fusion splicer, 4X microscope, magnifying lamp, UV curing lamp, fiber polish equipment.
  • Laser Systems: We house a wide range of laser systems 350, 488, 532, 633, 785 nm, including pulsed and tunable lasers, and other light sources. These lasers provide the essential light sources required for various optical sensing techniques, enabling our probes to deliver accurate and reliable results.
  • Spectrometers and Detectors: High-resolution spectrometers and sensitive detectors are employed to analyze the signals generated by our probes. These devices ensure that our probes provide accurate and detailed information for applications such as fluorescence, Raman or OCT.

Team

We are a multidisciplinary research team consisting of physicists, chemists, optical and biomedical engineers.

Mads S. Bergholt

Principal Investigator

Mads received his MSc. in optics from the University of Southern Denmark and his Ph.D. in Biomedical Engineering from National University of Singapore. He was a Marie Curie Fellow at Imperial College London. His research interests include biomedical optics, optical imaging, advanced endoscopy and artificial intelligence.

Shiyue Liu (Dora)

Postdoctoral Research Associate

Dora received her BSc. in Biomedical engineering and PhD in Biochemistry from The Chinese University of Hong Kong. She is currently a Postdoctoral Research Associate at King's College London. Her research interests include multimodal biomedical imaging, Raman and FTIR spectroscopy, laser and cell/tissue interaction.

Jianrong Qiu

Postdoctoral Research Associate

Jianrong Received his MSc. in information engineering and Ph.D. in optical engineering from Zhejiang University. He is currently a Postdoctoral Research Associate at King's College London. His research interests include optical coherence tomography, advanced endoscopy and Raman spectroscopy.

Marija Dimitrievska

PhD student

Marija received her MSci in Molecular Genetics from King’s College London. With a strong research background in gene editing and the investigation of cancer mutational signatures, she is now pursuing her PhD at the same institution. She works on developing a novel approach for molecular characterisation of chronic wounds in Recessive Dystrophic Epidermolysis Bullosa, utilising Raman spectroscopy and DESI-Mass Spectrometry.

Vishal Kumar

PhD student

Mr Vishal Kumar is currently a full-time doctoral student at King's College London. He received his integrated master's degree from Indian Institute of Science Education and Research (IISER) Mohali with a major in Physics and a minor in Data Sciences. He has research experience in applications of Artificial Intelligence (AI) and development of different biomedical diagnostic modalities such as Photoacoustic and Optical-CT systems. He is currently exploring Raman spectroscopy as a modality for Post-traumatic Osteoarthritis (PTOA) diagnosis.

Youxi Zhang

Research Assistant

Youxi received her MEng in Aeronautical Engineering from Imperial College London and her MSc in Physics at King’s College London. Her research interest includes optical instrumentation and deep learning

Alumni

Dr. Conor Horgan, Dr Elzbieta Stepula, Dr Steven Vanuytsel, Dr Magnus Jensen (PhD) Christina Gidarie (MSc), Kaur Palwinder (MRes), Khouj Osama (MRes), Ben Bowen (MSc), Margarita White (MSc), Chloe Roberts (MSc), Preveen Surendranathan (MSc),Youxi Zhang (MSc)

Contact us

We are located in a multidisciplinary clinical environment at Guy's Hospital, King's College London.

Contact Information

Label-Free Bioimaging Laboratory
King's College London
Centre for Craniofacial and Regenerative Biology
Floor 17, Tower Wing
Great Maze Pond, London SE1 9RT
mads.bergholt@kcl.ac.uk

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