The bright light of biophotonics

High speed, low cost and non-invasiveness – is biophotonics the future of clinical diagnostics? Professor Martin Leahy takes us through this growing and diverse discipline

Light is at the heart of all biophotonics research. Biophotonics is a relatively new but rapidly growing discipline which uses light to view and analyse living tissues and cells to detect, diagnose and treat diseases such as cancer, heart disease and Alzheimer’s. The interaction of light with matter results in absorption, fluorescence, reflection and scattering of the beam which can tell us information about the molecule or structure.

The European Commission identified photonics and imaging as technologies of exceptional importance for a knowledge-based economy, with the photonics industry in Europe worth approximately €58billion. Europe’s aging population means a substantial increase in the levels of many age related diseases and an associated increase in health care costs in the coming years. The speed of results and general non-invasiveness of biophotonic diagnostic methods have major cost advantages for public health systems.

The field brings together biologists, physicists, mathematicians, chemists and clinicians to harness advances in technology to meet clinical needs. This multi-disciplinary approach and collaboration is required to fully exploit the power of photonics for clinical applications. Biophotonics research has led to advances in medicine with which we are all familiar e.g. X-Rays, laser eye surgery and endoscopy. We now have the capability to view single molecule, cell, organ and whole body function using a range of complementary techniques including microscopy (Light, Electron, Atomic Force), Spectroscopic Imaging, and Mesoscopic Imaging (which capture 3D information). These advances in technology are being coupled with biology and medicine to revolutionise healthcare.

Researchers in the National Biophotonics and Imaging Platform, Ireland (NBIPI), are pushing the boundaries of imaging applications to understand biological processes underpinning both normal cellular function and disease, and to develop novel diagnostic tools for clinicians. The platform was established in 2007 following a €31M investment from the Higher Education Authority to provide an integrated national access and training infrastructure in research, education, technology development and industry collaboration. Over 500 high impact publications and an additional €25M awarded in competitive funding demonstrate the high quality research which is ongoing.

A number of innovative research strands involving applications such as label free imaging, vibrational spectroscopic characterisation of tissue and nanobiophotonics are producing results for the platform. Professor Martin Leahy based in the Tissue Optics and Microcirculation Imaging (TOMI) group in the National University of Ireland, Galway has established a world leading facility for microcirculation imaging. Their research focuses on ‘label free’ imaging techniques such as Optical Coherence Tomography (OCT), Laser Speckle and TiVi (Tissue Viability) Imaging to study the microcirculation, which is the movement of blood through the vasculature via arterioles, venules and capillaries. Aberrant microcirculation is a signature of many diseases including cancer, diabetes and macular degeneration. The application of these imaging techniques will lead to the development of inexpensive point of care tools for early detection of microvasculature deregulation.  Several imaging methods have already been developed by Prof Leahy’s group for the 6.5 billion people who don’t have access to high cost medical technology including development of a Cellular phone-based photoplethysmographic imaging monitoring of heart rate, heart rate variability and respiration. This was developed in response to World Health Organisation advice that resting heart rate alone is a strong indicator of impending cardiac failure. The app enabled Apps (e.g. instantheartrate and iPhysio) are available on Android and iPhone platforms with more than ten million users based on this algorithm and idea.

The group also are developing novel photoacoustic tomography (PAT) system technology for both microcirculation and deep tissue imaging. This technique couples optics with ultrasound imaging and can provide images comparable to a MRI or CT, but without the high associated costs. Commercially available imaging techniques such as MRI and CT typically use either extrinsic markers (labels) or harmful ionizing radiation which can cause problems ranging from toxicity, difficulty in delivery and system perturbations. PAT employs a label free methodology which will be of particular benefit to developing countries, where, even if medical imaging equipment is available, it often lies unused due to a lack of trained personnel and expensive running costs.

Researchers working in this area predict that in a few years PAT will be widely used in clinical practice. This is due to the fact that PAT works at far greater depths (up to 7cm) than other optical-imaging techniques such as confocal microscopy or optical-coherence tomography (> 1 mm). 3D images obtained of internal structures such as blood vessels and organs can be used to help guide biopsy needles and gastrointestinal endoscopies and measure oxygen levels in tissue, thereby helping to determine whether tumours are malignant or not. The information produced by PAT can also assess drug delivery and uptake within tissue; useful information for pharmaceutical companies.

Professor Hugh Byrne and Professor Fiona Lyng in the Focas Institute based in Dublin Institute of Technology have recently taken  a research project from the lab to a commercial reality. Raman and Infared microspectroscopic techniques were used to develop a novel diagnostic tool in cervical cancer diagnosis. The technology has been licensed following validation in clinical testing. Raman scattering can provide information on the types of bonds present in a structure, using a high intensity (laser) light source. The Raman process can be thought of as raising the energy of a molecule to a “virtual” state with re-emission at identical (Rayleigh) and shifted (Raman) frequencies which can be used to identify the molecule present. The research project was based on the capabilities of Raman spectroscopy to ‘finger print’ materials and therefore to characterise differences between normal and tumour tissue. A biobank of pathologically defined tissue and cellular material can be created and subjected to subsequent characterisation using Raman spectroscopy. In this way a database of normal, cancerous and precancerous spectral signatures can be established, against which unseen samples can be classified.

Using Nanobiophotonics to develop new assays for assessing cardiovascular system is another exciting collaboration between clinicians and NBIPI scientists. Nanobiophotonics involves a fusion of nanotechnology, biomedical science and photonics to study biological systems and offers huge potential benefits for intracellular diagnostics. Platelet assays are commonly used to detect the presence of activated platelets, which is a strong indicator of stroke and cardiovascular abnormalities. A range of novel dyes and nanoparticle probes which bind to integrins (the complexes involved in platelet activation) have been developed. These probes combine luminescence (fluorescence or phosphorescence) with resonance Raman and surface enhanced Raman imaging and environmental sensing ability (e.g. pH and O2) which provide detailed information about the molecule and enhance our understanding of the platelet events in thrombosis. An enhanced platelet activation assay using specifically engineered high brightness silica nanoparticles as ‘super-labels’ is also developed. The high brightness probe allows for more sensitive detection upon binding to activated integrins while the silica coating ensures biocompatibility, allowing the effective delivery of the nanoparticle containing the fluorescent probe into the cell without interferences from the cellular environment. These assays are also being modified to predict drug effect in cardiovascular diseases in patients taking antiplatelet therapy and clinical trials are ongoing for this.

High resolution imaging of the platelet surface using Atomic force microscopy and Electron microscopy is being used to identify morphological differences between platelets from healthy versus diseased patients by measuring cell height, surface area and roughness. A large population study is underway to more accurately identify these differences which may identify mechanisms involved in progression of the disease and develop assays for early detection. Biophotonics brings the in depth understanding of biological processes together with advanced technology to develop solutions to existing clinical problems. The future of biophotonics research and development is bright and promises to have enormous societal impact in the years to come.

Author: Professor Martin Leahy is Chair of Applied Physics at the National University of Ireland Galway. He is currently the scientific director of the National Biophotonics and Imaging Platform, Ireland (NBIPI) and an adjunct professor of the Royal College of Surgeons in Ireland. He is a Fellow of the Institute of Physics in Ireland, the Royal Academy of Medicine in Ireland and is a Fellow of SPIE.