We use light to develop advanced diagnostic tools, wearable sensors, and microscale robots for studying diseases and enabling minimally invasive treatments.
What we do
We use photonics to develop new technologies for medicine and to study the pathophysiology of disease. This includes new and improved diagnostic tools as well as microscale robotic devices for therapeutic applications. We use a variety of optical techniques for this purpose such as fluorescence, Raman and diffuse reflectance spectroscopy, as well as microscopy and interferometry. We develop devices ranging from wearable sensors and fibre-optic probes for minimally invasive diagnostics through to microscale robots for cellular-scale manipulation and therapy.
Why it is important?
Our research has a number of potential clinical applications including improved monitoring of clinical therapies and interventions (e.g. in inflammatory bowel disease and malnutrition), early diagnosis of infection, and even margin mapping in tumour resection surgery.
How can it benefit patients?
The devices we are developing can potentially provide less invasive and lower cost diagnostics. In turn, this may facilitate patient benefits including earlier diagnosis, earlier identification of relapse (e.g. in therapy response monitoring applications), more widespread deployment and more comfortable patient experiences (e.g. through use of less invasive probes and sensors).
Meet the team
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Journal articleThompson AJ, Power M, Yang G-Z, 2018,
A micro-scale fiber-optic force sensor fabricated using direct laser writing and calibrated using machine learning
, Optics Express, Vol: 26, Pages: 14186-14200, ISSN: 1094-4087Fiber-optic sensors have numerous existing and emerging applications spanning areas from industrial process monitoring to medical diagnosis. Two of the most common fiber sensors are based on the fabrication of Bragg gratings or Fabry-Perot etalons. While these techniques offer a large array of sensing targets, their utility can be limited by the difficulties involved in fabricating forward viewing probes (Bragg gratings) and in obtaining sufficient signal-to-noise ratios (Fabry-Perot systems). In this article we present a microscale fiber-optic force sensor produced using direct laser writing (DLW). The fabrication entails a single-step process that can be undertaken in a reliable and repeatable manner using a commercial DLW system. The sensor is made of a series of thin plates (i.e. Fabry-Perot etalons), which are supported by springs that compress under an applied force. At the proximal end of the fiber, the interferometric changes that are induced as the sensor is compressed are read out using reflectance spectroscopy, and the resulting spectral changes are calibrated with respect to applied force. This calibration is performed using either singular value decomposition (SVD) followed by linear regression or artificial neural networks. We describe the design and optimization of this device, with a particular focus on the data analysis required for calibration. Finally, we demonstrate proof-of-concept force sensing over the range 0-50 μN, with a measurement error of approximately 1.5 μN.
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Journal articleVysniauskas A, Lopez Duarte I, Thompson AJ, et al., 2018,
Surface functionalisation with viscosity-sensitive BODIPY molecular rotor
, Methods and Applications in Fluorescence, Vol: 6, ISSN: 2050-6120Surface functionalisation with viscosity sensitive dyes termed ‘molecular rotors’ can potentially open up new opportunities in sensing, for example for non-invasive biological viscosity imaging, in studying the effect of shear stress on lipid membranes and in cells, and in imaging contacts between surfaces upon applied pressure. We have functionalised microscope slides with BODIPY-based molecular rotor capable of viscosity sensing via its fluorescence lifetime. We have optimised functionalisation conditions and prepared the slides with the BODIPY rotor attached directly to the surface of glass slides and through polymer linkers of 5 kDa and 40 kDa in mass. The slides were characterised for their sensitivity to viscosity, and used to measure viscosity of supported lipid bilayers during photooxidation, and of giant unilamellar vesicles lying on the surface of the slide. We conclude that our functionalised slides show promise for a variety of viscosity sensing applications.
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Book chapterThompson AJ, Yang G-Z, 2018,
Tethered and Implantable Optical Sensors
, Implantable Sensors and Systems, Editors: Yang, Publisher: Springer, Pages: 439-505, ISBN: 978-3-319-69747-5Optical imaging and sensing modalities have been used in medical diagnosis for many years. An obvious example is endoscopy, which allows remote wide-field imaging of internal tissues using optical fibers and/or miniature charge-coupled device (CCD) cameras. While techniques such as endoscopy provide useful tools for clinicians, they do not typically allow a complete diagnosis to be made. Instead, physical biopsies may be required to confirm or refute the presence of disease. Furthermore, endoscopic procedures are both invasive and time-consuming. As such, much research is currently directed toward the development of devices that can provide a complete in vivo diagnosis without the requirement for a physical biopsy. Ideally, such devices should also be minimally or non-invasive, and they should provide immediate identification of disease at the point of care. Additionally, there is significant interest in the development of implantable diagnostic devices that can be left within patients’ bodies for extended periods of time (for several days or longer). Such systems could be used for automated disease diagnosis, and example applications include the detection of post-surgical infections as well as monitoring of the health status of patients undergoing chemotherapy. This chapter focuses on the development of optical instruments that can provide in situ diagnosis at the point of care, with an emphasis on progress towards miniature devices that may function as implants in the future.
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Journal articlePower MC, Thompson A, Anastasova-Ivanova S, et al., 2018,
A monolithic force-sensitive 3D microgripper fabricated on the tip of an optical fiber using 2-photon polymerization
, Small, Vol: 14, Pages: 1703964-1-1703964-10, ISSN: 1613-6810Microscale robotic devices have myriad potential applications including drug delivery, biosensing, cell manipulation, and microsurgery. In this work, a tethered, 3D, compliant grasper with an integrated force sensor is presented, the entirety of which is fabricated on the tip of an optical fiber in a single-step process using 2-photon polymerization. This gripper can prove useful for the interrogation of biological microstructures such as alveoli, villi, or even individual cells. The position of the passively actuated grasper is controlled via micromanipulation of the optical fiber, and the microrobotic device measures approximately 100 µm in length and breadth. The force estimation is achieved using optical interferometry: high-dimensional spectral readings are used to train artificial neural networks to predict the axial force exerted on/by the gripper. The design, characterization, and testing of the grasper are described and its real-time force-sensing capability with an accuracy below 2.7% of the maximum calibrated force is demonstrated.
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Conference paperSchmitz A, Thompson AJ, Berthet-Rayne P, et al., 2017,
Shape sensing of miniature snake-like robots using optical fibers
, IEEE International Conference on Intelligent Robots and Systems (IROS), Publisher: IEEE, Pages: 947-952, ISSN: 2153-0858Snake like continuum robots are increasingly used for minimally invasive surgery. Most robotic devices of this sort that have been reported to date are controlled in an open loop manner. Using shape sensing to provide closed loop feedback would allow for more accurate control of the robot's position and, hence, more precise surgery. Fiber Bragg Gratings, magnetic sensors and optical reflectance sensors have all been reported for this purpose but are often limited by their cost, size, stiffness or complexity of fabrication. To address this issue, we designed, manufactured and tested a prototype two-link robot with a built-in fiber-optic shape sensor that can deliver and control the position of a CO 2 -laser fiber for soft tissue ablation. The shape sensing is based on optical reflectance, and the device (which has a 4 mm outer diameter) is fabricated using 3D printing. Here we present proof-of-concept results demonstrating successful shape sensing - i.e. measurement of the angular displacement of the upper link of the robot relative to the lower link - in real time with a mean measurement error of only 0.7°.
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Journal articleThompson AJ, Hughes M, Anastasova S, et al., 2017,
The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction
, Nature Reviews Gastroenterology and Hepatology, Vol: 14, Pages: 727-738, ISSN: 1759-5045Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical biopsy techniques — which can provide minimally invasive or noninvasive alternatives to biopsy — could offer other routes to validation and could potentially be used as point-of-care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care.
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Conference paperPower M, Seneci CA, Thompson AJ, et al., 2017,
Modelling & characterization of a compliant tethered microgripper for microsurgical applications
, International Conference on Manipulation, Automation and Robotics at Small Scales, MARSS 2017, Publisher: IEEEThe development of microscale surgical tools could pave the way for truly minimally invasive microsurgical procedures. This work demonstrates the application of direct laser writing (DLW) using two-photon polymerization (TPP), a rapid prototyping microfabrication technique, to create a tethered, passively actuated three-dimensional gripper with potential applications in microbiopsy. A microgripper design was devised, modelled and optimized. The gripper was then fabricated and characterized for validation of the theoretical model. The results demonstrate that modelling the behavior of compliant microtools provides a useful approximation for the observed trends and, thus, can be utilized in the design of TPP tools. Future work on the incorporation of viscoelastic material into the model will further improve agreement between the predicted and experimental performance.
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Journal articleKuimova MK, Mika JT, Thompson AJ, et al., 2016,
Measuring the viscosity of the Escherichia coli plasma membrane using molecular rotors
, Biophysical Journal, Vol: 111, Pages: 1528-1540, ISSN: 1542-0086The viscosity is a highly important parameter within the cell membrane, affecting the diffusion ofsmall molecules and, hence, controlling the rates of intra-cellular reactions. There is significantinterest in the direct, quantitative assessment of membrane viscosity. Here we report the use offluorescence lifetime imaging microscopy (FLIM) of the molecular rotor BODIPY C10 in themembranes of live Escherichia coli (E. coli) bacteria to permit direct quantification of the viscosity.Using this approach we investigated the viscosity in live E. coli cells, spheroplasts and liposomesmade from E. coli membrane extracts. For live cells and spheroplasts the viscosity was measured atboth room temperature (23o C) and the E. coli growth temperature (37o C), while the membraneextract liposomes were studied over a range of measurement temperatures (5-40o C). At 37o C werecorded a membrane viscosity in live E. coli cells of 950 cP, which is considerably higher than thatpreviously observed in other live cell membranes (e.g., eukaryotic cells, membranes of Bacillusvegetative cells). Interestingly, this indicates that E. coli cells exhibit a high degree of lipid orderingwithin their liquid-phase plasma membranes.
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Conference paperThompson AJ, Koziej L, Williams H, et al., 2016,
Towards optical fibre based Raman spectroscopy for the detection of surgical site infection
, BiOS, SPIE Photonics West, Publisher: SPIESurgical site infections (SSIs) are common post-surgical complications that remain significant clinical problems, as they are associated with substantial mortality and morbidity. As such, there is significant interest in the development of minimally invasive techniques that permit early detection of SSIs. To this end, we are applying a compact, clinically deployable Raman spectrometer coupled to an optical fibre probe to the study of bacteria, with the long term goal of using Raman spectroscopy to detect infection in vivo. Our system comprises a 785 nm laser diode for excitation and a commercial (Ocean Optics, Inc.) Raman spectrometer for detection. Here we discuss the design, optimisation and validation of this system, and describe our first experiences interrogating bacterial cells (Escherichia coli) in vitro. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
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Journal articleThompson AJ, Cannon BC, Wackel PL, et al., 2016,
Electrocardiographic abnormalities in elite high school athletes: comparison to adolescent hypertrophic cardiomyopathy
, BRITISH JOURNAL OF SPORTS MEDICINE, Vol: 50, Pages: 105-+, ISSN: 0306-3674
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