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
Results
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Conference paperMaleki AN, Thompson A, Runciman MS, et al., 2023,
A soft hydraulic endorectal actuator for prostate radiotherapy
Despite advances in radiotherapy, motion error remains a challenge in prostate radiotherapy. Rectal obturators and endorectal balloons may reduce motion error and improve outcomes but have limitations. We aimed to create a deployable rectal obturator with precise angle control to personalise to a patient's rectal anatomy, by using an antagonistic pair of "muscle"actuators to flex and extend the device. Results on deployability, angle control, and radial stiffness are presented here. The device can be compressed down to 16 x 3 x 91 mm, and be deployed to maximum dimensions of 24 x 25.5 x 77 mm. The device provides radial stiffness that may be sufficient to stabilise the rectum during radiotherapy. Angle control can be achieved with an average change of 7.5°/ml inflation in the extensor actuator.
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Journal articleWei J, Monfort Sanchez E, Avery J, et al., 2022,
Non-invasive assessment of intestinal permeability in healthy volunteers using transcutaneous fluorescence spectroscopy
, Methods and Applications in Fluorescence, Vol: 10, Pages: 1-9, ISSN: 2050-6120The permeability of the intestinal barrier is altered in a multitude of gastrointestinal conditions such as Crohn's and coeliac disease. However, the clinical utility of gut permeability is currently limited due to a lack of reliable diagnostic tests. To address this issue, we report a novel technique for rapid, non-invasive measurement of gut permeability based on transcutaneous ('through-the-skin') fluorescence spectroscopy. In this approach, participants drink an oral dose of a fluorescent dye (fluorescein) and a fibre-optic fluorescence spectrometer is attached to the finger to detect permeation of the dye from the gut into the blood stream in a non-invasive manner. To validate this technique, clinical trial measurements were performed in 11 healthy participants. First, after 6 h of fasting, participants ingested 500 mg of fluorescein dissolved in 100 ml of water and fluorescence measurements were recorded at the fingertip over the following 3 h. All participants were invited back for a repeat study, this time ingesting the same solution but with 60 g of sugar added (known to transiently increase intestinal permeability). Results from the two study datasets (without and with sugar respectively) were analysed and compared using a number of analysis procedures. This included both manual and automated calculation of a series of parameters designed for assessment of gut permeability. Calculated values were compared using Student's T-tests, which demonstrated significant differences between the two datasets. Thus, transcutaneous fluorescence spectroscopy shows promise in non-invasively discriminating between two differing states of gut permeability, demonstrating potential for future clinical use.
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Journal articleFletcher E, Thompson A, Ashrafian H, et al., 2022,
The measurement and modification of hypoxia in colorectal cancer: overlooked but not forgotten
, Gastroenterology Report, Vol: 10, Pages: 1-13, ISSN: 2052-0034Tumour hypoxia is the inevitable consequence of a tumour’s rapid growth and disorganised, inefficient vasculature. The compensatory mechanisms employed by tumours, and indeed the absence of oxygen itself, hinder the ability of all treatment modalities. The clinical consequence is poorer overall survival, disease-free survival, and locoregional control. Recognising this, clinicians have been attenuating the effect of hypoxia, primarily with hypoxic modification or with hypoxia activated pro-drugs, and notable success has been demonstrated. However, in the case of colorectal cancer (CRC), there is a general paucity of knowledge and evidence surrounding the measurement and modification of hypoxia, and this is possibly due to the comparative inaccessibility of such tumours. We specifically review the role of hypoxia in CRC, and focus on: the current evidence for the existence of hypoxia in CRC, the majority of which originates from indirect positron emission topography (PET) imaging with hypoxia selective radiotracers; the evidence correlating CRC hypoxia with poorer oncological outcome, which is largely based on the measurement of Hypoxia Inducible Factor (HIF) in correlation with clinical outcome; the evidence of hypoxic modification in CRC, of which no direct evidence exists, but is reflected in a number of indirect markers; the prognostic and monitoring implications of accurate CRC hypoxia quantification and its potential in the field of precision oncology; and the present and future imaging tools and technologies being developed for the measurement of CRC hypoxia, including the use of blood oxygen level dependent (BOLD) MRI imaging and diffuse reflectance spectroscopy.
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Conference paperS√°nchez EM, Avery J, Darzi A, et al., 2022,
Development of a wearable fluorescence sensor for non-invasive monitoring of gut permeability
, The Hamlyn Symposium on Medical Robotics: "MedTech Reimagined", Publisher: The Hamlyn Centre, Imperial College London London, UK, Pages: 65-66<jats:p>Inflammatory bowel disease, coeliac disease, and malnutrition have all been linked to changes in intestinal function, particularly gut permeability [1]. Endoscopic biopsies and histopathology, together with chemical tests such as Lactulose:Mannitol assays, are the techniques currently used to assess permeability in the clinic. However, those methods are either invasive, unable to offer comprehensive diagnoses, or challenging to perform in infants [2]. Further, the mechanisms and in interactions behind function the the gut’s aforementioned (and additional) disorders are currently not well understood. As a result, novel diagnostic technologies that provide non-invasive and accurate measurements of intestinal permeability (and other aspects of gut function) could have major therapeutic implications [3]. Recent studies in both humans and animals have shown the potential of transcutaneous fluorescence spectroscopy to provide information relevant to gastrointestinal (GI) function – including gut permeability – in a non-invasive manner (e.g. [4-7]). This method entails oral administration of a fluorescent contrast agent combined with the use of a wearable probe to non-invasively measure the permeation of the contrast agent from the gut into the blood stream, thereby facilitating measurements of gut leakiness/permeability and other clinically relevant GI functions [4-7]. However, the devices that have been used for this purpose are laser-based, large and expensive, which make them unsuitable for large scale clinical deployment [4-7].To address the above limitations, here we report preliminary results from a compact fluorescence spectroscopy sensor for transcutaneous monitoring of gut function. The primary functionality of the device is to detect fluorescence signals at the skin
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Conference paperMonfort Sanchez E, Avery J, Darzi A, et al., 2022,
Development of a compact fluorescence spectroscopy sensor for non-invasive monitoring gut function
, Optica Biophotonics Congress: Biomedical Optics 2022, Publisher: Optica Publishing GroupMonitoring gut permeability is currently either invasive, inaccurate or difficult to perform in infants. We present a compact fluorescence sensor that overcomes some of these limitations, paving the way for non-invasive gut permeability monitoring.
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Journal articleWei J, Nazarian S, Teare J, et al., 2022,
A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn’s disease
, BMC Gastroenterology, Vol: 22, ISSN: 1471-230XBackground:A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn’s disease.Methods:A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn’s disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn’s disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn’s, active Crohn’s, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model.Results:Pooled LMR in healthy controls was 0.014 (95% CI: 0.006–0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089–0.178) and 0.037 (95% CI: 0.019–0.055). In active and inactive Crohn’s disease, pooled LMRs were 0.093 (95% CI: 0.031–0.156) and 0.028 (95% CI: 0.015–0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (4) healthy controls and inactive Crohn’s (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (5) healthy controls and active Crohn’s (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (6) active Crohn’s and inactive Crohn&rsquo
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Journal articleMbuki R, Chileya S, Thompson AJ, et al., 2021,
Rapid testing of gut permeability using oral fluorescein and confocal laser endomicroscopy in Zambian adults
, TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, Vol: 115, Pages: 1226-1228, ISSN: 0035-9203- Author Web Link
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Journal articleThompson A, Bourke C, Robertson R, et al., 2021,
Understanding the role of the gut in undernutrition: what can technology tell us?
, Gut, Vol: 70, Pages: 1580-1594, ISSN: 0017-5749Gut function remains largely underinvestigated in undernutrition, despite its critical role in essential nutrient digestion, absorption and assimilation. In areas of high enteropathogen burden, alterations in gut barrier function and subsequent inflammatory effects are observable but remain poorly characterised. Environmental enteropathy (EE)—a condition that affects both gut morphology and function and is characterised by blunted villi, inflammation and increased permeability—is thought to play a role in impaired linear growth (stunting) and severe acute malnutrition. However, the lack of tools to quantitatively characterise gut functional capacity has hampered both our understanding of gut pathogenesis in undernutrition and evaluation of gut-targeted therapies to accelerate nutritional recovery. Here we survey the technology landscape for potential solutions to improve assessment of gut function, focussing on devices that could be deployed at point-of-care in low-income and middle-income countries (LMICs). We assess the potential for technological innovation to assess gut morphology, function, barrier integrity and immune response in undernutrition, and highlight the approaches that are currently most suitable for deployment and development. This article focuses on EE and undernutrition in LMICs, but many of these technologies may also become useful in monitoring of other gut pathologies.
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Journal articleLett A, Lim A, Skinner C, et al., 2021,
Rapid, non-invasive measurement of gastric emptying rate using transcutaneous fluorescence spectroscopy
, Biomedical Optics Express, Vol: 12, Pages: 4249-4264, ISSN: 2156-7085Gastric emptying rate (GER) signifies the rate at which the stomach empties following ingestion of a meal and is relevant to a wide range of clinical conditions. GER also represents a rate limiting step in small intestinal absorption and so is widely assessed for research purposes. Despite the clinical and physiological importance of gastric emptying, methods used to measure GER possess a series of limitations (including being invasive, slow or unsuitable for certain patient populations). Here, we present a new technique based on transcutaneous (through-the-skin) fluorescence spectroscopy that is fast, non-invasive, and does not require the collection of samples or laboratory-based analysis. Thus, this approach has the potential to allow immediate reporting of clinical results. Using this new method, participants receive an oral dose of a fluorescent contrast agent and a wearable probe detects the uptake of the agent from the gut into the blood stream. Analysis of the resulting data then permits the calculation of GER. We compared our spectroscopic technique to the paracetamol absorption test (a clinically approved GER test) in a clinical study of 20 participants. Results demonstrated good agreement between the two approaches and, hence, the clear potential of transcutaneous fluorescence spectroscopy for clinical assessment of GER.
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Journal articleKim J, Yeatman E, Thompson A, 2021,
Plasmonic optical fiber for bacteria manipulation—characterization and visualization of accumulation behavior under plasmo-thermal trapping
, Biomedical Optics Express, Vol: 12, Pages: 3917-3933, ISSN: 2156-7085In this article, we demonstrate a plasmo-thermal bacterial accumulation effect usinga miniature plasmonic optical fiber. Combined action of far-field convection and a near-fieldtrapping force (referred to as thermophoresis)—induced by highly localized plasmonicheating—enabled large-area accumulation of Escherichia coli. The estimated thermophoretictrapping force agreed with previous reports, and we applied speckle imaging analysis to mapthe in-plane bacterial velocities over large areas. This is the first time that spatial mapping ofbacterial velocities has been achieved in this setting. Thus, this analysis technique providesopportunities to better understand this phenomenon and to drive it towards in vivo applications.
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