Travel Grant for Adaptive Optics in CARS Microscopy

Lead Research Organisation: University of Strathclyde
Department Name: Inst of Photonics


Optical microscopy has provided scientists, and clinicians, with the ability to image living tissue with sub-cellular resolution for around four hundred years. This ability has lead to a number of scientific breakthroughs both in the life and physical sciences. Significant advances in general optics have frequently been achieved by the desire to image samples with increasing resolution so that the finest structures can be resolved. Indeed just over 130 years ago Abbe advanced the study of optics with his work on improved optical microscopy with the introduction of diffraction theory and the study of optical aberrations. However, crucial to all forms of microscopy is the ability to have contrast between the different structures present within the sample. For most of the last fifty years this has been provided by the addition of fluorescent labels to the sample culminating in the use of genetically modified samples so that they naturally express a fluorescent label. Even in this case the sample is not in its natural state and thus the method is not practical for a number of samples, and makes the application of microscopy to living tissue difficult, and impossible for many clinical applications.Coherent Anti-Stokes Raman Scattering (CARS) microscopy is a method by which optical microscopy can be undertaken using the spectral fingerprint of a specific molecule as the contrast agent. By tuning two laser sources to the correct wavelengths specific molecular spectral features can be excited enabling highly specific microscopy. The process is non-linear and hence the imaging volume is restricted in three dimensions offering the ability of the microscope to naturally generate high resolution optical slices which can be reconstructed to produce three dimensional images.However, as one wishes to image more deeply into a sample the laser light has to pass through the sample and is aberrated leading to a loss of signal and spatial resolution at depths much beyond 100microns. This problem is similar to that faced by ground based astronomers examining space through the atmosphere. Through the use of active optical elements (adaptive optics) they have demonstrated that the atmospheric aberrations can be removed, or at least minimised. Previously we have adopted the same technology to multiphoton and confocal microscopy with considerable success; however, both of these imaging modalities require the addition of fluorescent compounds to the sample in some form thus perturbing the natural state of the tissue. The aim of this project is to explore the use of adaptive optics (AO) in CARS microscopy by linking, for two weeks, world leading expertise in both the application of adaptive optics to microscopy and CARS imaging. By fitting the Institute of Photonics AO system to the Harvard CARS microscope we will rapidly be able to determine if AO has a role to play in CARS microscopy as is strongly suspected. This proposal thus offers a rapid, low cost route to the evaluation of AO for in-depth CARS microscopy.


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Description The project demonstrated that adaptive optics can be integrated into CARS microscopes and improve but the depth and resolution of CARS microscopy. Beyond the science the short but focused visit also demonstrated a very practical and efficient way that science can be undertaken between labs through an initial two day focused planning visit (by the PI) and then a two week laboratory visit by the two post docs who had worked on the method in the UK.
Exploitation Route The use of CARS is being considered for medical diagnosis and hence the increased depth and resolution offered by the AO route may have a longer term role to play. The work was published in peer reviewed journals and also in several conference proceedings and has since been included in two book chapters by the PI.

A patent was filed and discussions are taking place with Olympus and Leica who have the non-exclusive rights from the Harvard group to sell CARS microscopes.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

Description EPSRC Responsive Mode
Amount £506,510 (GBP)
Funding ID EP/I010173/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2010 
End 04/2014
Description Harvard link on AO In CARS Microscopy 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution We have developed a patent on the research undertaken
Collaborator Contribution Harvard brought the CARS microscopy skills, we brought the adaptive optics
Impact Several papers and publications as well as a patent listed elsewhere
Start Year 2007
Title System and Method for Employing Adaptive Optics to Provide Enhanced Signals in CARS Microscopy 
Description American Patent Submission December 2007 
IP Reference  
Protection Patent granted
Year Protection Granted
Licensed No