Final Report Summary - NULTIS (Next generation ultrafast continuously running imaging system for biomedical applications) In general, statistically rare phenomena are ubiquitous in almost every branch of science. Capture and investigation of these rare phenomena requires real-time high-throughput measurement instruments. In cancer research, for example, it is believed that metastasis, not the parent tumor, causes 90% of cancer deaths. Efficiently capturing circulating tumor cells (CTCs) from patient’s blood is essential for diagnosis of cancer metastasis. Unfortunately, these CTCs are so scarce that current diagnostic tools are incapable to monitor them with sufficient throughput and statistical accuracy. This project, under the support by the Marie-Curie CIG scheme, aimed to provide a step change in ultrafast optical imaging for high-throughput single-cell analysis by merging state-of-the-art optical communications hardware, advanced signal processing algorithms, with bioengineering technology.Over the past four years, work has been carried out following on the proposed research programmes. A summary of the research work performed to achieve the project’s objectives is summarized below.(1) A prototype ultrafast imaging system has been built at the University of Kent. With the support from this CIG grant, a PhD student has been recruited to work on this project. The PhD student has successfully graduated with fruitful outcome produced through this project. The University of Kent has also made significant investment in photonics research, which allows me to purchase a mode-locked fibre laser, a 100GS/s real-time oscilloscope and a 12GS/s arbitrary waveform generator, which are all essential equipment for the proposed research. (2) During the first half phase of the project, we successfully developed a new generation ultrafast single-pixel optical imaging system which addresses some remaining challenges in existing ultrafast imaging approach based on photonic time stretch. In particular, an all-fibre-compatible spectrally-encoded imaging system has been developed. The use of a highly-efficient in-fibre diffraction grating eliminates the need for bulky and lossy free-space gratings, hence reducing the volume of the imaging system, improves energy efficiency, and increases system stability. This work has been published in OSA journal Optics Letters. The all-fiber spatial disperser is particularly attractive to time stretch ultrafast imaging systems, as it is inherently compatible with optical fibers that provide chromatic dispersion. Complex and lossy light coupling between optical fibers and free-space gratings is therefore avoided. The developed ultrafast imaging system does not only improve the energy efficiency, but also the imaging resolution thanks to its full-aperture illumination structure. This work was presented at OSA FiO 2016 conference as a Post-deadline paper and later published in Nature journal Scientific Reports. In addition, phase-contrast imaging feature has been investigated and applied in ultrafast optical coherence tomography imaging. Compressive sensing concept has been implemented in the optical domain to significantly reduce the massive data volume, which is an inherent result of continuous ultrafast imaging capturing. This work has been published in IEEE Photonics Journal as an Invited Paper. Other work to address the data challenge in ultrafast imaging include: development of spatial-domain and spectral domain photonic implementation of compressive sensing based on spatial pattern modulation and real-time random spectral filtering. These work has been recently reported in several major international photonics conference. Moreover, spatial encoding fading effect in photonic time stretch systems has been investigated as well with results published in IEEE Photonics Technology Letters. (3) To fulfil the overall objectives of the project, in the last phase of the project, we focused on the application of the developed ultrafast imaging system for biomedical application, in particular advanced real-time high-throughput single cell screening. A new class of automated single-cell flow microscopy merging state-of-the-art optical communication, microfluidics and DSP technologies has been developed for image-based cell recognition. A high-speed cell recognition algorithm has been developed improve the detection speed by over 150% while maintaining good recognition accuracy. The algorithm provides a promising solution for high-throughput and automated cell imaging and classification in general ultrafast flow cytometer imaging platform. This work has been published in SPIE Journal of Biomedical Optics. The main outcomes of this project and their potential impact are summarized as follows. (i) This CIG grant has significantly helped the fellow to achieve important scientific results, with 7 journal papers so far published under acknowledgement of funding support of this grant in top journals such as Optics Letters, Scientific Reports, IEEE Photonics Technology Letters, IEEE Photonic Journals, et al. and 6 other conference papers related to this project presented in major international photonics conferences, including invited and post-deadline presentations. These publications made considerable contributions to the field of ultrafast imaging.(ii) This CIG grant has also greatly supported the fellow to develop his smooth transition in research from the USA to the UK as a Lecturer then promoted to a Senior Lecturer at the University of Kent. The fellow has created his independent research team at Kent, consisting of 4 PhD students, and 5 visiting academics. The PhD student directly supported by this CIG grant has successfully graduated and is currently working as a postdoctoral fellow in Kings College London on biomedical imaging research. In addition, wide research collaborations with UK, EU and overseas institution have been developed as well, supported not only by this CIG grant, but also by UK Royal Society, and China Scholarship Council. (iii) This CIG grant provides an essential initial support to the follow’s independent research at the University of Kent. The research programme developed within this project has not only produced significant publications, but also helped the fellow to obtain other funding opportunities supported by the Royal Society, and EPSRC to continue his research practice in ultrafast imaging in particular and photonics in general. This CIG grant together with other awarded grants all greatly help promote the research and generate impact beyond the academia. The fellow’s research has attracted interest from the newly created National Centre on Healthcare Photonics and the fellow is collaborating with the new centre to work towards practical imaging product, which has potential for commercialization as a preclinical imaging tool within five years and within a decade for clinical use and will fill a broad spectrum of medical device markets.
