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
Dr Belal Ahmad
Dr Belal Ahmad
Imperial College Research Fellow
Dr Qian Chen
Dr Qian Chen
Clinical Research Fellow
Dr Ahmed Ezzat
Dr Ahmed Ezzat
Research Postgraduate
Dr Nilanjan Mandal
Dr Nilanjan Mandal
Research Associate in Optical Sensing for LMICs
Dr Alexander J Thompson
Dr Alexander J Thompson
Senior Lecturer in Biomedical Sensing
Mr Zeyu Wang
Mr Zeyu Wang
Research Postgraduate
Results
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Journal articlePhiri T, Weatherill J, Monford-Sanchez E, et al., 2024,
Novel gastrointestinal tools (GI Tools) for evaluating gut functional capacity in adults with environmental enteropathy in Zambia and Zimbabwe: A cross-sectional study protocol [version 1; peer review: awaiting peer review]
, F1000Research, Vol: 13, ISSN: 2046-1402Environmental enteropathy (EE) is a highly prevalent subclinical inflammatory intestinal disorder associated with growth failure, impaired neurocognitive development, poor response to oral vaccines, and micronutrient deficiencies. However, EE research and clinical trials are hampered by the lack of non-invasive tools for measuring intestinal function in detail. This study aims to develop new tools for the measurement of multiple domains of gut functional capacity. Methods The GI TOOLS project is a cross-sectional study that will recruit adults aged 18-65 years with EE in Lusaka, Zambia. Each participant will undergo assessment of gut functional capacity using novel near-point-of-care tools and provide multiple samples for detailed laboratory analyses. Participants will also undergo endoscopy for collection of duodenal biopsies. Novel techniques include stable isotopes approaches to measuring digestion, absorption, and bidirectional transmucosal amino acid flux, a non-invasive fluorescence tool for real-time evaluation of gut permeability, and assessment of reverse permeation of intravenous antibiotics to be carried out separately in Zimbabwe. Stool and duodenal microbiome sequencing using MinION sequencing, metabolome analysis applied to plasma and intestinal fluids, blood immune cell phenotyping, in vitro epithelial barrier models, and duodenal immunohistochemistry will also be used to explore EE in depth. These will all be integrated with gold standard histology and mucosal morphometry, alongside lactulose permeation data, and stool and plasma biomarker analysis. The protocol has been approved by ethics committees and regulators in Zambia, Zimbabwe, and the UK. Participants will give informed consent before they can participate Anticipated outcomes Based on this extensive phenotyping, tests will be developed which can be simplified and refined for use in adults and children with EE, and for clinical trials. Findings from this project will be disseminated through i
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Conference paperWatson AF, Haanaes N, Chambers R, et al., 2024,
Towards label-free flow cytometry for automated cell identification using diffuse reflectance spectroscopy
, SPIE PHOTONICS EUROPE, Publisher: SPIEFlow cytometry is widely used for cell identification and characterization and involves labelling biological and clinical samples with fluorochrome-conjugated antibodies specific to cell markers. This requires use of expensive exogenous reagents and necessitates complex pre-processing of samples. Additionally, extensive challenges arise in clinical samples consisting of highly plastic and heterogenous cell types observed in diseases such as cancer. As such, it is challenging to apply flow cytometry to point-of-care diagnostic applications. To address this issue, we investigated the combination of diffuse reflectance spectroscopy (DRS), microfluidics and machine learning to offer rapid, low-cost, label-free cell identification for potential deployment at the point of care. To achieve this, we utilized a compact fibre-optic diffuse reflectance spectrometer with multi-depth sensing capability. This system was applied to a proof-of-concept cell identification study where we were able to discriminate triple negative breast cancer cells from healthy fibroblasts using commercially available flow channel slides (Ibidi GmbH, channel dimensions: 5 mm width, 0.4 mm height). However, we observed high interexperimental variability, which was partially attributed to the relatively large fluidic channels. Thus, we investigated in-house fabrication of microfluidics of varying channel widths (0.6-2mm). To this end, we used a Mars ELEGOO 3D printer and commercially available printing materials to batch fabricate optically and mechanically viable microfluidic chips that were both cheap and customizable. Using these in-house microfluidic devices, we demonstrated DRS-based discrimination of cancer cells of different origins, further indicating the potential of this approach for point-of-care cell identification/characterization. Ultimately, we hope this work will lead to the development of cheap, deployable, and accurate point-of-care tools for rapid, label-free cell identification.
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Conference paperMandal N, Sanchez EM, Avery J, et al., 2024,
A wireless semi-wearable sensor for assessment of gut function in low-resource settings
, Optics and Biophotonics in Low-Resource Settings X, Publisher: SPIEEnvironmental enteric dysfunction (EED) is a subclinical disorder of intestinal function common in tropical countries and settings of poverty and economic disadvantage. EED manifests during infancy and is associated with undernutrition, poor sanitation, and gut infections. EED is characterised by inflammation, reduced absorptive capacity, and reduced barrier function (i.e., increased permeability) in the small intestine. The precise mechanisms underlying changes in gut barrier function (and other aspects of intestinal function) in EED remain elusive. Furthermore, current diagnostic methods to assess gut permeability (e.g., endoscopic biopsies or permeability assays such as the Lactulose:Mannitol test) are invasive, unreliable and/or challenging to perform in infants and patients with other coexisting urological conditions. Consequently, there is an urgent need to develop diagnostic technologies that can non-invasively and affordably monitor intestinal permeability in low-resource settings where EED is prevalent.To address this need, we present a prototype semi-wearable, wireless sensor for non-invasive assessment of intestinal permeability via transcutaneous fluorescence spectroscopy. The approach relies on the ingestion of a fluorescent contrast agent (fluorescein) and the subsequent detection of its permeation from the gut into the bloodstream using a wearable probe. We outline the development of the semi-wearable sensor and report preliminary in vivo deployment. This showcases the potential of transcutaneous fluorescence spectroscopy as a wearable and non-invasive diagnostic tool for assessing gut function in low-resource settings.
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Journal articleMonfort Sanchez E, Avery J, Wei J, et al., 2024,
Transcutaneous fluorescence spectroscopy: development and characterization of a compact, portable, fiber-optic sensor
, Journal of Biomedical Optics, ISSN: 1083-3668 -
Journal articleEnnis A, Nicdao D, Kolagatla S, et al., 2023,
Two‐photon polymerization of sugar responsive 4D microstructures
, Advanced Functional Materials, Vol: 33, ISSN: 1616-301XStimuli-responsive hydrogels have attracted much attention owing to the versatility of their programmed response in offering intelligent solutions for biomimicry applications, such as soft robotics, tissue engineering, and drug delivery. To achieve the complexity of biomimetic structures, two photon polymerization (2PP) has provided a means of fabricating intricate 3D structures from stimuli-responsive hydrogels. Rapid swelling hydrogel microstructures are advantageous for osmotically driven stimuli-response, where actuation speed, that is reliant on the diffusion of analytes or bioanalytes, can be optimized. Herein, the flexibility of 2PP is exploited to showcase a novel sugar-responsive, phenylboronic acid-based photoresist. This offers a remarkable solution for achieving fast response hydrogel systems that have been often hindered by the volume-dependent diffusion times of analytes to receptor sites. A phenylboronic acid-based photoresist compatible with 2PP is presented to fabricate stimuli-responsive microstructures with accelerated response times. Moreover, microstructures with programmable actuation (i.e., bending and opening) are fabricated using the same photoresist within a one-step fabrication process. By combining the flexibility of 2PP with an easily adaptable photoresist, an accessible fabrication method is showcased for sophisticated and chemo-responsive 3D hydrogel actuators.
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Journal articleKim JA, Hou Y, Keshavarz M, et al., 2023,
Characterization of bacteria swarming effect under plasmonic optical fiber illumination
, Journal of Biomedical Optics, Vol: 28, Pages: 1-15, ISSN: 1083-3668SignificancePlasmo-thermo-electrophoresis (PTEP) involves using plasmonic microstructures to generate both a large-scale convection current and a near-field attraction force (thermo-electrophoresis). These effects facilitate the collective locomotion (i.e., swarming) of microscale particles in suspension, which can be utilized for numerous applications, such as particle/cell manipulation and targeted drug delivery. However, to date, PTEP for ensemble manipulation has not been well characterized, meaning its potential is yet to be realized.AimOur study aims to provide a characterization of PTEP on the motion and swarming effect of various particles and bacterial cells to allow rational design for bacteria-based microrobots and drug delivery applications.ApproachPlasmonic optical fibers (POFs) were fabricated using two-photon polymerization. The particle motion and swarming behavior near the tips of optical fibers were characterized by image-based particle tracking and analyzing the spatiotemporal concentration variation. These results were further correlated with the shape and surface charge of the particles defined by the zeta potential.ResultsThe PTEP demonstrated a drag force ranging from a few hundred fN to a few tens of pN using the POFs. Furthermore, bacteria with the greater (negative) zeta potential ( | ζ | > 10 mV) and smoother shape (e.g., Klebsiella pneumoniae and Escherichia coli) exhibited the greatest swarming behavior.ConclusionsThe characterization of PTEP-based bacteria swarming behavior investigated in our study can help predict the expected swarming behavior of given particles/bacterial cells. As such, this may aid in realizing the potential of PTEP in the wide-ranging applications highlighted above.
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Journal articleDeLorey C, Davids JD, Cartucho J, et al., 2023,
A cable‐driven soft robotic end‐effector actuator for probe‐based confocal laser endomicroscopy: Development and preclinical validation
, Translational Biophotonics, Vol: 5, ISSN: 2627-1850Soft robotics is becoming a popular choice for end-effectors. An end-effector was designed that has various advantages including ease of manufacturing, simplicity and control. This device may have the advantage of enabling probe-based devices to intraoperatively measure cancer histology, because it can flexibly and gently position a probe perpendicularly over an area of delicate tissue. This is demonstrated in a neurosurgical setting where accurate cancer resection has been limited by lack of accurate visualisation and impaired tumour margin delineation with the need for in-situ histology. Conventional surgical robotic end-effectors are unsuitable to accommodate a probe-based confocal laser endomicroscopy (p-CLE) probe because of their rigid and non-deformable properties, which can damage the thin probe. We have therefore designed a new soft robotic platform, which is advantageous by conforming to the probe's shape to avoid damage and to facilitate precision scanning.
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Conference paperFletcher T, Monfort-Sanchez E, Keshavarz M, et al., 2023,
Quantifying hypoxia with diffuse reflectance spectroscopy for advanced prognostication and real-time response monitoring in rectal cancer: an in vivo feasibility study
, Optical Fibers and Sensors for Medical Diagnostics, Treatment and Environmental Applications XXIII, Publisher: SPIE, Pages: 1-6, ISSN: 1605-7422Tumour hypoxia is a critical factor in treatment failure and resistance, and its accurate measurement with diffuse reflectance spectroscopy (DRS) could be used for prognostic and response monitoring purposes. In this in vivo characterisation study, we sequentially measured oxygenation trends over the entire course of tumour growth in mice using a multi-depth, fibre-optic DRS probe. Results demonstrated a clear downtrend in oxygenation over time. This progression was not always linear, with significant heterogeneity over time and between mice. Our findings will be further validated against gold standards prior to investigating whether hypoxia can be used to predict radiotherapy responses.
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Journal articleLi X, Keshavarz M, Kassanos P, et al., 2023,
SERS detection of breast cancer-derived exosomes using a nanostructured Pt-black template
, Advanced Sensor Research, Vol: 4, Pages: 1-12, ISSN: 2751-1219At present, there are no cancer treatments that are both non-invasive and highly accurate. New tests that can diagnose cancer at an early stage would help to facilitate such improved therapies, and many recent studies have focused on the development of liquid biopsy tests for this purpose. Exosomes are extracellular vesicles secreted by cells as a means of communication that can be simply collected from blood samples. Current studies have shown the potential of surface-enhanced Raman spectroscopy (SERS) in differentiating cancerous cells from healthy cells. Herein, a bespoke platinum-black (Pt-black) SERS template is developed—via a cost-effective fabrication method of electroplating—to detect malfunctioned (cancerous) exosomes. The results demonstrate that the Pt-black SERS substrate exhibits stable and consistent spectra, which produces the high reproducibility required for a reliable diagnostic template. More importantly, using the Pt-black SERS template allows for the differentiation of cancer-derived exosomes (extracted from 4T1 cells—a triple-negative breast cancer cell line) and exosomes from healthy fibroblast cells with an 83.3% sensitivity and a 95.8% specificity. This study establishes the potential of the Pt-black template in detecting cancerous exosomes and lays a solid foundation for future studies in the clinical application of SERS in cancer diagnosis.
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Conference paperMonfort Sánchez E, Avery J, Gan J, et al., 2023,
A compact fluorescence sensor for low-cost non-invasive monitoring of gut permeability in undernutrition
, Optics and Biophotonics in Low-Resource Settings IX, Publisher: SPIE, Pages: 1-7, ISSN: 1605-7422Undernutrition is associated with approximately 45% of deaths among children under the age of 5. Furthermore, in 2020, around 149 million children suffered impaired physical/cognitive development due to lack of adequate nutrition. Environmental enteropathy (EE) is associated with undernutrition and is characterized by a multifaceted breakdown in gut function, including an increase in intestinal permeability that can lead to inflammatory responses. However, the role and mechanisms associated with EE (particularly gut permeability) are not well understood. This is partly because current techniques to assess changes in gut permeability, such as endoscopic biopsies, histopathology and chemical tests such as Lactulose:Mannitol assays, are either highly invasive, unreliable or difficult to perform on specific groups of patients (such as infants and patients with urine retention problems). Therefore, low-cost, non-invasive and reliable diagnostic tools are urgently needed for better evaluation of intestinal permeability. Here, we present a compact transcutaneous fluorescence spectroscopy sensor for non-invasive evaluation of gut permeability and report the first in vivo data collected from volunteers in an undernutrition trial. Using this technique and device, fluorescence signals are detected transcutaneously after oral ingestion of a fluorescent solution. Preliminary results demonstrate the potential use of the presented sensor for clinical assessment of gut permeability in low-income settings.
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