Page 1 Cancer Diagnostic Technology Summit 5 - 7 December 2023 Sponsored by:
Page 2 LifeArc takes science ideas and helps turn them into life-changing medical breakthroughs Our teams are experts in diagnostics discovery and data, alongside drug discovery, technology transfer, and intellectual property. Our goal is to help early ideas reach the next phase of development through advice, expertise, funding and collaboration. We are currently in the process of defining a new strategy for childhood cancer. To find out more, visit lifearc.org
Page 3 Welcome to the 4th Annual Cancer Diagnostic Technology Summit 2023. In this Book of Abstracts you will find abstracts for each presentation and brief biographies of each speaker. [Regrettably, at the time of publication one or two abstracts were still missing but we will add these back if possible] Please note that the abstract and biography information remains the copyright of each author. You should not share, publish or otherwise transmit this information without the written consent of the author. I would like to express my thanks to a number of people. Firstly to LifeArc for generously sponsoring this conference and for their commitment to the objectives of the conference - facilitating the adoption of new technology for the early diagnosis of cancer. Secondly to all the authors of the conference presentations. Your hard work in producing your conference contribution is very much appreciated, as are your efforts in developing new cancer diagnostic tests. Finally to Ian Cree and Pedro Estrela for help in developing the program, and to Maryam Daneshpour and Suzanne Sisto Brand for doing the background research. The Conference would not have happened without you. I hope you will find the conference interesting, valuable and inspiring. Your comments after the event are invited and are always appreciated. Michael Brand PhD SM FRSC michael@sensor100.com Conference Chair
Page 4 Early cancer detection: challenges for implementation Prof Ian Cree CanTech Limited Detection of cancers at an early stage benefits patients, who have improved chance of survival, and healthcare systems, which have fewer costs to bear as a result. However, early cancer detection is not easy, despite the success of screening programmes for common cancer types. In the UK, current screening programmes for breast cancer (mammography), colorectal cancer (FIT), and cervical cancer (HPV) are successful, but have issues of coverage which remains just over 70% for breast and cervical cancer screening, but only 60% for colorectal cancer screening. There is interest in new programmes for lung and prostate cancers, but these have issues of cost effectiveness which are hard to overcome. A general blood test that would detect all (or even most) cancers at a stage when they are limited in size would be game-changing (1,2), but despite some progress, this remains a matter for research.While it may be feasible to develop a high sensitivity general test for cancer, using multiple biomarkers (2,3), there will be need to fit these into existing diagnostic pathways without over-stressing the existing service by potential over-diagnosis (4). 1. Cree IA. Improved blood tests for cancer screening: general or specific? BMC Cancer. 2011 Nov 30;11:499. PMID: 22128772 2. Uttley L,Whiteman BL,Woods HB, Harnan S, Philips ST, Cree IA; Early Cancer Detection Consortium. Building the Evidence Base of Blood-Based Biomarkers for Early Detection of Cancer:A Rapid Systematic Mapping Review. EBioMedicine. 2016 Aug;10:164-73. PMID: 27426280 3. Cree IA, Uttley L, Buckley Woods H, Kikuchi H, Reiman A, Harnan S,Whiteman BL, Philips ST, Messenger M, Cox A,Teare D, Sheils O, Shaw J; UK Early Cancer Detection Consortium.The evidence base for circulating tumour DNA blood-based biomarkers for the early detection of cancer: a systematic mapping review. BMC Cancer. 2017 Oct 23;17(1):697. PMID: 29061138 4.Yadav K, Cree I, Field A,Vielh P, Mehrotra R. Importance of Cytopathologic Diagnosis in Early Cancer Diagnosis in Resource-Constrained Countries. JCO Glob Oncol. 2022 PMID: 35213215 Ian Cree MBChB, PhD, FRCPath Ian Cree is a pathologist, currently working as a consultant to the medical diagnostics industry. He is recently retired from his post as an international civil servant, based at the International Agency for Research on Cancer (IARC) in Lyon where he lead the WHO Classification of Tumours, responsible for the ‘WHO Blue Books’ and the Evidence Synthesis and Classification branch, responsible for the IARC Monographs and the IARC Handbooks. He is an Honorary Professor of Pathology at the Institute of Ophthalmology, part of University College London; and at the University of Coventry. He has previously held posts as the foundation Yvonne Carter Professor of Pathology at Warwick Medical School, Consultant Pathologist at University Hospital Coventry and Warwickshire, Professor of Histopathology at the University of Portsmouth and as the founding Director of the Efficacy and Mechanism Evaluation (EME) programme for the UK National Institute of Health Research (NIHR) Evaluation Trials and Studies Coordinating Centre. Until April 2015 he was a member of the UK National Institute of Clinical Excellence (NICE) Diagnostics Advisory Committee, joining at its inception. He was founding Chair of the Inter-specialty Committee on Molecular Pathology for the Royal College of Pathologists (2011 – 2015) and chaired its Research Committee (2015 – 2017).Trained as a general pathologist with a PhD in immunology, Ian’s research career has been based on investigating disease mechanisms to improve diagnosis and treatment, particularly for cancer. He has a developed a number of molecular diagnostics methods and led the UK Early Cancer Detection Consortium (2012 – 2017). He has a major interest in the management of translational research. He has published more than 300 papers, and 11 books.
Page 5 The PinPointTest, a Machine Learning-based test for Cancer in symptomatic patients. Dr Nigel Sansom PinPoint Data Science ‘PinPoint Data Science has for the last six years been developing ‘The PinPoint Test’, an AI Machine Learning-based blood test for cancer. It comprises regulated software medical devices for nine NHS urgent cancer referral pathways and is designed to assist clinicians by providing the risk that a given patient has cancer. It is affordable, cost-effective, and has been deployed in the NHS for service evaluation since 2020. Because the core technology of the PinPoint Test is a combination of machine learning and statistical modelling, it is possible to use improved training data sets to produce new versions of the test with improved diagnostic accuracy performance. Such improved data sets arise naturally from use of the test, and post-market surveillance (clinical follow-up). In partnership with the West Yorkshire and Harrogate Cancer Alliance and the broader NHS West Yorkshire ICS, the recent service evaluation has produced promising results for the Lower GI, Breast, Urological and Skin urgent pathways for symptomatic patients. PinPoint is now working with NHS partners to clinically deploy the test, and through continual improvement as we collect more and more data, will look to move the dial on early detection’. Dr Nigel Sansom Originally trained in molecular pathology, Nigel has over twenty year’s-experience of senior level roles in the pharmaceutical and biotech industries, academia, consultancy and the NHS. He has developed an international reputation for his involvement in innovation and the commercial development of medical technology and diagnostics having been one of the founding managers of the NHS National Innovation Centre. Nigel advises governmental grant awarding bodies on life sciences, and medical technology, and has been a mentor to participants in numerous technology accelerators. He joined the founders’ team at PinPoint Data Science in 2017 as Executive Chair and as part of the Business Team, Nigel plays an active role in helping the company develop a Machine Learning-based blood test for cancer.
Page 6 Harnessing data mining for predictive modeling in ocular melanoma cancer care Dagmar Schneider, nandatec research GmbH, Germany Data mining, a crucial element of Personalized Medicine, improves pattern recognition by analyzing extensive datasets, identifying genetic markers, and assessing treatment responses. Uveal melanoma, the predominant eye malignancy, presents significant treatment challenges. Early diagnosis, detection of gene mutations (GNA11, GNAQ), tumor dimensions and individual pathophysiological factors play a crucial role for patient outcome.The rarity, coupled with high mortality and metastasis rates of uveal melanoma, poses obstacles for clinical studies for personalized and targeted therapies. Here we present the combination of predictive modeling and a microfluidic human cell-based eye model for drug development.(3,4) Next-generation sequencing and imaging techniques are used to obtain the genetic and clinical data for predictive modeling. This cost-efficient eye model reveals new targeted treatment pathways and optimizes interventions for patients with uveal melanoma. Furthermore, the combination of artificial intelligence with a human cell based eye model enables long-term research, transforming how we approach the complexity of this challenging malignancy. 1. Shain,A.H., Bagger, M.M.,Yu, R. et al.The genetic evolution of metastatic uveal melanoma. Nat Genet 51, 1123–1130 (2019). 2. Riechardt AI, Kilic E, Joussen AM.The Genetics of Uveal Melanoma: Overview and Clinical Relevance. Klin Monbl Augenheilkd. 2021 Jul;238(7):773-780. 3. Schneider D., Lange T., Jamrozik M.: Microfluidic artificial eye with AI for COVID-19 testing; NIBS- Nanotech for Life Science;Technical Digest; p.19, 05.08.2021. 4. Schneider D., Lange T., Jamrozik M.: 3 D-printed artificial eye with artificial intelligence for allergy testing; Berlin-Brandenburger Optik Tag, excellence in photonics,WFBB, online conference; 31.08.2020. Dagmar Schneider studied Human Medicine at Philipps-University of Marburg and University Hamburg and Biochemistry/Molecular Biology at the Christian-Albrechts-University of Kiel, Germany. She is educated in Biostatistics, clinical epidemiology and clinical trials by Harvard Medical School. D. Schneider has a strong background in Bioinformatics, basic research and led cross-functional teams at the Fraunhofer EMB, Lübeck, as Head of the Cell Technology Laboratory. Her experience, innovative ideas and deep understanding of complex issues in different research areas led to her work as Scientific Business Manager at the Technology Transfer platform Tandem/Medisert, Center of Excellence for Technology and Engineering in Medicine and the BioMedTech Campus in Lübeck. In 2013 Schneider founded nandatec GmbH, a Nanobiotechnology research SME located in Lübeck and Innovation Center Itzehoe, where she functions as Managing Director until today. In 2015 nandatec received the KfW-award Gründerchampions Schleswig-Holstein 2015. She was nominated for the Publikumspreis KfW-Award and Startup of the Year Award at the Micronano conference,Amsterdam in 2016. 2017 Schneiderwas one of three finalists of the IB.SH entrepreneurship award. During her career she was involved in fundraising for projects of over 28 million €. D. Schneider was a member of the selection committee Gründungsstipendium Kiel. Until today she is member of the extended Board of Life Science Nord e.V. and Supervisory Board of LSN Management GmbH. In order to strengthen the technology transfer D. Schneider has memberships in the Signal Transduction Society, the German Society for Stem Cell Research, and functions as Ambassador for nandatec at Biopeople Denmark.
Page 7 The challenges of sample size in liquid biopsy Matthew Owens BioCaptiva Dr Matthew Owens is the Lead Scientist with BioCaptiva, a medical device manufacturer working to resolve the common challenge of low cfDNA inputs in liquid biopsy. Dr Owens is the originator of the msX™ polymer technology for the recovery of DNA directly from biological fluids.This has been applied in their BioCaptis™ device for the recovery of cfDNA directly from circulating plasma as part of an apheresis circuit, which is shortly commencing first-in-human trials. Dr Owens has a background in biomaterial research, completing his PhD in high throughput biomedical polymer discovery at the University of Edinburgh in 2016.
Page 8 Evolution trial: Proof-of-mechanism for a diagnostic probe using an on-breath volatile reporter for lung cancer Dr Mariana Ferreira Leal Owlstone Medical Analysis of volatile metabolites in breath represents an attractive non-invasive diagnostic modality, and potential screening tool, for lung cancer. One of the key challenges is the optimization of the signal-tonoise ratio in a complex matrix as breath. Exogenous Volatile Organic Compound (EVOC®)-probes can be used to detect a cancer-associated enzyme activity and therefore utilised to generate sensitive and specific on-breath signals for lung cancer.We ran a proof-of-mechanism study to evaluate whether administration of D5-ethyl-β-D-glucuronide EVOC-probe specific to tumor-associated extracellular β-glucuronidase results in the production of a unique marker on breath. For this, we first demonstrate that β-glucuronidase is present in the lung cancer microenvironment independent of the tumor stage or histological subtype and therefore an attractive target for a lung cancer diagnostic test. In vitro, we confirmed the probe cleavage by β-glucuronidase. In humans, the administration of the EVOC-probe demonstrated an excellent safety and tolerability profile and D5-ethanol was detected on breath of a subset of individuals after intravenous probe administration.This study provides a proof of mechanism for the cleavage of D5-ethyl-β-D-glucuronide in humans and lay the foundation of a follow-up study to evaluate the diagnostic performance of this breath test for early detection of lung cancer. Dr Mariana Ferreira Leal is a Lead Translational Scientist – Team Lead at Owlstone Medical. At the beginning of her career, she focused on the investigation of gastric cancer diagnostic and prognostic biomarkers. She led her own projects and team before moving to The Institute of Cancer Research in London, where she became interested in the investigation of biomarkers of response to hormone therapies given to breast cancer patients as well as the investigation of mechanism of action and resistance to several compounds in breast cancer models. This knowledge brought her to work in a drug discovery biotech focusing on the modulation of transcription factors in breast cancer. At Owlstone Medical, Dr Mariana Ferreira Leal is focused on the discovery and development of non-invasive tests for lung cancer diagnosis and/or screening based on Breath Biopsy.
Page 9 Optical biosensing of hypermethylated DNA biomarkers in urine for early cancer diagnostics Dr MarkVerheijden1 and Dr Luc Scheres2 1. Qurin Diagnostics 2. Surfix Diagnostics Qurin Diagnostics and Surfix Diagnostics form a partnership with the aim to develop a platform for diagnosis of cancer starting with urine as liquid biopsy. Specifically, hypermethylated DNA markers will be used to allow early diagnostics. Qurin works in 3 pillars: biomarker discovery, PCR development and optical biosensing. In the biomarker discovery pillar, Qurin developed an AI-based bioinformatics pipeline to analyze (public) datasets to distill the most relevant biomarker panels for cancer detection. In the PCR development pillar, these panels are translated into methylation specific PCR (qMSP) IVD tests.The first qMSP test is currently in the Design and Development process, aiming to bring selected high performing biomarker panels to the patient as soon as possible.This approach will pave the way for future market entry of the optical biosensing platform, which will provide faster, cheaper and lab-free analysis with no need for bisulfite conversion.The optical platform is being co-developed together with Surfix diagnostics. It consists of a read-out system as well as a disposable microfluidic cartridge containing the small (3x3.5mm) optical chip which allows a 6-plex detection with internally referenced sensors.These chips are transformed to highly sensitive biosensors by Surfix’ wafer-scale, surface selective coating technology and subsequent probe immobilization. Mark L.Verheijden, PhD Program Director Biosensing Mark studied chemical engineering with a master in material science. His PhD has been at the interface of supramolecular chemistry, material science and biology. He studied the interactions of cells, viruses and peptides at functionalized sensor surfaces. At Qurin Diagnostics, he applies this multidisciplinary background to develop a highly sensitive biosensing pipeline for the detection of methylated DNA in urine for cancer diagnostics. In his role as program director, he oversees the technological development of both the urine sample preparation and the biosensing.
Page 10 CRISPR-Cas-amplified urinary biomarkers for multiplexed and portable cancer diagnostics Prof Liang Hao Boston University Integration of precision diagnostics and new personalized therapies holds significant promise to improve the management of a variety of diseases, including cancer. Besides the tumor-intrinsic genetic alterations, tissue-environmental features during tumor progression and invasion, such as the aberrant extracellular matrix remodeling, stromal composition, and immune components, open engineering opportunities to develop novel biomarkers and therapeutic targets. In this talk, I will focus on an emerging paradigm in precision diagnostics, the synthetic biomarkers, exogenous probes that can be locally activated by altered proteases in the tumor microenvironment to generate molecular reporters in the biofluid.To overcome the limitations often associated with molecular biomarkers (nonspecificity, dilution, and rapid degradation), we engineered the synthetic biomarker platform with enhanced specificity and clinical actionability by developing CRISPR-Cas-amplifiable urinary reporters to detect and differentiate disease states at the Point-of-Care.This study highlights the use of chemical tools with built-in cancer-reactive modules, embracing a vision for precision health through integrated strategies: identification, monitoring, and intervention in a personalized manner. Dr. Liangliang Hao is an Assistant Professor in the Department of Biomedical Engineering, Molecular Biology, Cell Biology & Biochemistry at Boston University, and Cancer Center at Boston Medical Center. She develops precision engineering solutions to improve the specificity, adaptability, and portability of cancer diagnostics and therapeutics. Prior to her professorship, she received her Ph.D. from Northwestern University under the guidance of Prof. Chad Mirkin and did her postdoctoral research in Prof. Sangeeta Bhatia’s lab at the Koch Institute for Integrated Cancer Research of MIT. Over her career, Dr. Hao has been awarded multiple honors and grants, including fellowships from the Howard Hughes Medical Institute, the American Cancer Society, an NIH Pathway to Independence Award, and a PhRMA Foundation Faculty Starter Award in Translational Medicine.
Page 11 Panel Discussion What is needed to take a diagnostic test from lab to clinic Panellists Prof Pedro Estrela (Moderator) Pedro Estrela is Professor of Biosensors and Bioelectronics at the Department of Electronic & Electrical Engineering and Director of the Centre for Bioengineering & Biomedical Technologies (CBio) at the University of Bath. Dr Simon Bayly Simon Bayly is Senior Business Manager -TranslationSenior Business Manager -Translation at The Francis Crick Institute, London Prof Ian Cree Ian Cree is a Director of CanTech Limited. He is a pathologist, previously Head of WHO Tumour Classification (WCT) Group and Head of the section of Evidence Synthesis and Classification, at the International Agency for Research on Cancer in Lyon, France. Dr David Jenkinson David Jenkinson is Head of Childhood Cancer Translational Challenge at LifeArc. He was formerly the Chief Scientific Officer at the Brain Tumour Charity.
Page 12 Decentralising cancer diagnostics using Lab-on-Chip technology – towards a lab-free model for clinical use Dr Melpomeni Kalofonou Imperial College London, Deparment of Electrical and Electronic Engineering The need for affordable and accessible diagnostic and monitoring technologies for cancer is now even greater, especially due to the recent repercussions of the pandemic and their indirect effect on patients with cancer.With the evolution of Lab-on-Chip technology for Point-of-Care testing, we are witnessing a convergence of engineering and sensing technologies for early screening, detection and monitoring of cancer, with advances in diagnostic testing, genotyping and DNA sequencing to have enabled a paradigm-shift in modern medicine and particularly in cancer research. From the moment of cancer diagnosis, to therapeutic monitoring and disease progression, the role of tumour-specific markers linked to different stages of tumour growth are of crucial importance. Liquid-biopsies can offer this through longitudinal monitoring of tumour specific molecular alterations for more targeted cancer profiling and prediction of therapeutic resistance. Molecular analysis platforms that are currently in use for target testing rely on laboratory-based equipment (qPCR/sequencing) and skilled operators and can be time-consuming and unaffordable for operation at a large scale, having not yet been clinically adopted for regular front-line testing. Lab-on-Chip technology in the form of sample-to-result systems has a great potential in Cancer Diagnostics, allowing the integration of thousands of chemical sensors, combined with electronics, instrumentation and microfluidics, capable of detecting molecular targets in minutes rather than hours. In this talk, I will present my research team’s latest developments in the design and testing of target-specific molecular methods, which are ‘microchip compatible’, for the detection of circulating-tumour DNA (ctDNA) mutations found in breast, colorectal and ovarian tumours, making the Lab-on-Chip approach as a viable option to assist future clinical evaluation and targeted treatment selection. Melpomeni Kalofonou is a Research Fellow and Cancer Technology Lead at the Centre for Bio-Inspired Technology, within the Department of Electrical and Electronic Engineering, Imperial College London. She has conducted pioneering work in the application of microchip technology for detection of cancer specific biomarkers, through design and fabrication of microchip devices, integrating chemical sensors with molecular biology assays, leading to the development of Lab-on-Chip systems for detection and computation of genetic and epigenetic targets. One of her key research areas is on ‘liquid-biopsy’ based cancer diagnostics using pH-sensitive microchip technology, which will enable detection of cancer specific mutations in the tumour derived fraction of circulating-free DNA in blood, providing a sample-to-result system for patient stratification and monitoring tumour progression. Dr Kalofonou graduated with an MEng Degree (Hons) in Electrical and Computer Engineering in 2007 from the University of Patras, Greece followed by an MSc in Biomedical Engineering, Department of Bioengineering in 2009 and a PhD in Biomedical Engineering, Department of Electrical and Electronic Engineering from Imperial College London in 2013. She continued as a Postdoctoral Researcher at the Centre for Bio-Inspired Technology where she became the Lead for Cancer Engineering and Technologies in 2016, starting a new research theme on the development of Lab-on-Chip devices and microchip compatible methods for detection of cancer-specific genetic and epigenetic markers linked to early detection, progression and personalisation of cancer therapy. Her CRUK-funded research focuses on the application of Lab-on-Chip technology for the detection of ctDNA mutations linked to breast cancer relapse and the prediction of resistance to treatment, expanding into other cancer types, such as ovarian and colorectal cancer, with her work to be currently focusing on the development of fast and accurate microchip-compatible chemistries for the detection of tumour-derived variants linked to early detection and prognosis of the disease.
Page 13 Point-of-care electrochemical sensors for cancer diagnosis and cancer management Prof Pedro Estrela Centre for Bioengineering & Biomedical Technologies (CBio) and Department of Electronic and Electrical Engineering, University of Bath, United Kingdom p.estrela@bath.ac.uk There is a great need for low-cost biosensor chips capable of parallel detection of cancer biomarkers to be used in portable instrumentation. In order to realise the promise of liquid biopsies, such devices need to be robust and provide a combination of high selectivity and sensitivity.As we move towards a telehealth model where patients under treatment or on surveillance test themselves or at community-level facilities, biosensors can further provide the speed, low cost and portability required for point-of-care testing. Electrochemical methods are inherently low-cost, miniaturisable and easily integrated into multiplexed systems for the parallel screening of panels of biomarkers. Of particular interest are biologically sensitive field-effect transistors (BioFETs) and impedance-based sensors (both Faradaic and non-Faradaic impedance). Improved selectivity and robustness can be provided by using synthetic molecules such as DNA aptamers, peptide aptamers (Affimers) and molecularly imprinted polymers as alternatives to antibodies. We have developed a range of biosensors for the multiplexed detection of protein biomarkers, microRNAs and cancer cells. Such biosensors can be integrated with microfluidics and electronic addressing for on-chip sample preparation (e.g. separation, pre-concentration), sensing and data transmission in fully functional Lab-on-Chip biodevices for point-of-care applications. Pedro Estrela is Professor of Biosensors and Bioelectronics at the Department of Electronic & Electrical Engineering and Director of the Centre for Bioengineering & Biomedical Technologies (CBio) at the University of Bath. He has a background in Physics (degree and Masters from the University of Lisbon, PhD from the University of Amsterdam) and started working in the field of biosensors in 2000 (University of Cambridge until 2008 and University of Bath since 2008). He is a member of the Steering Committee of the Centre for Therapeutic Innovation (CTI) and committee member of the Cancer Research at Bath (CR@B) network. Prof. Estrela’s research focuses on the development of label-free electrical, electrochemical and plasmonic biosensors for a wide range of applications such as medical diagnostics and environmental monitoring. He has over 165 peer-reviewed publications (Scopus h-index 39), many of them in high impact journals in the fields of biosensors and analytical chemistry. He is an Associate Editor for the journals Biosensors & Bioelectronics, Scientific Reports, Sensors, Frontiers in Sensors and Advanced Devices & Instrumentation and Specialty Chief Editor in Frontiers in Lab on a Chip Technologies.
Page 14 Electrochemical strips to manage cancer in decentralized settings Pro Stefano Cinti Department of Pharmacy, University of Naples Federico II Via D. Montesano 49, 80131 Naples stefano.cinti@unina.it Point-of-care testing (PoC) is revolutionizing the healthcare sector improving patient care in daily hospital practice and allowing reaching even remote areas. In the frame of cancer management, the design and validation of PoC enabling the non-invasive, rapid detection of cancer markers is urgently required to implement liquid biopsy. However, despite substantial advances in sensing technologies, the development, preparation, and use of self-testing devices is still confined to specialist laboratories and users. Decentralized analytical devices will enormously impact daily lives, enabling people to analyze diverse clinical, environmental, and food samples, evaluate them and make predictions to improve quality of life, particularly in remote, resource-scarce areas. In recent years, paper-based analytical tools have attracted a great deal of attention; the well-known properties of paper, such as abundance, affordability, lightness, and biodegradability, combined with features of printed electrochemical sensors, have enabled the development of sustainable devices that drive (bio)sensors beyond the state of the art.A wide overview regarding application ranging from DNA to miRNA detection will be provided, with the aim in showing the potentialities of portable electrochemical biosensors for improving society involvement in monitoring circulating nucleic acids (and not only) associated to cancer. Stefano Cinti is an Associate Professor at the Department of Pharmacy, University of Naples “Federico II”. He obtained a Ph.D. in Chemical Sciences in 2016 in the group headed by Prof. Giuseppe Palleschi at the University of Rome “Tor Vergata”. He leads the uninanobiosensors Lab (uninanobiosensors.com) at University of Naples “Federico II”, and his research interests include the development of electrochemical sensors, portable diagnostics, paper-based devices and nanomaterials. During his research activity, he had the opportunity to spend a period abroad in Finland, U.K., U.S., Germany, and Spain. He has published more than 80 papers in peer-reviewed journals, with an H-index of 35 and > 4000 citations.Among all the prizes and certificates, in 2022 he was awarded with the early career award from International Society of Electrochemistry in Analytical Electrochemistry, in 2022 he was awarded with Biosensors 2022 Young Investigator Award, in 2023 he was awarded a Sensor Division Early Career Award by ECS and in 2022 he has been recognized as the World’s Top 2% Scientists. He is the coordinator of the Chemical Cultural Diffusion group of Italian Chemical Society. He is the Chair of AMYC-BIOMED, a multidisciplinary conference for young chemists in the biomedical sciences. He is very active in communicating science to nonspecialized audience through TV shows, radio, and magazine.
Page 15 Improving triage and diagnosis of skin cancer patients in primary care setting through non-invasive sampling and detection of molecular bio markers from skin interstitial fluid Prof Sylvain Ladame Imperial College London, Department of Bioengineering Skin cancer diagnosis is most commonly derived from visual or digital inspection of a skin lesion by a trained professional, ideally including dermoscopy. Identification of suspicious skin lesions in primary care are typically followed by an urgent referral, leading to a skin biopsy and histopathological examination, in suspicious cases.Whilst primary care clinicians are generally very accurate at identifying melanoma skin lesions that require intervention, only 3% of patients sent on the urgent referral pathway end up being diagnosed in secondary care with melanoma.This means that a large volume of patients is subjected to unnecessary invasive procedures (tissue biopsies) resulting in unnecessary morbidity.A technology that could help general practitioners (GPs) in primary care more effectively screen out patients who do not require dermatological assessment and biopsy would allow significant savings from the £35M currently spent on unnecessary diagnostic procedures every year for suspected skin cancer. Our solution is to (1) identify and validate, within skin interstitial fluid (IF), highly specific and highly sensitive molecular biomarkers for melanoma; (2) develop new technologies capable of detecting these new biomarkers that could be used by care providers to improve the quality of referral.We will be presenting how microneedle patches made of highly swellable, bespoke hydrogels can be engineered to diagnose melanoma with high sensitivity and specificity based on the detection of cancer-specific microRNA biomarkers, sampled near the suspicious lesion, where their concentration is the highest.We will be demonstrating how sampling IF proximal to the lesion presents a highly promising strategy to achieve greater levels of deregulation of tumour-specific biomarkers and detect, thus enabling easier and more accurate diagnosis with unprecedented spatiotemporal resolution. Dr Sylvain Ladame did his undergraduate studies in Chemistry at the University of Poitiers (19941997). He then went to carry out a PhD at the University of Toulouse (1997-2001). He then travelled to the University of Cambridge (UK) to work for five years (2001-2006) as a post-doctoral researcher in the group of Sir, Prof. Shankar Balasubramanian within the department of Chemistry. In 2006, he joined the CNRS as an Assistant Professor (Chargé de Recherche 1ère classe, CR1) in Strasbourg (France) and started his independent academic career as a junior group leader within the ‘Institut de Science et d’Ingénierie Supramoléculaires’ (ISIS). Four years later, in 2010, he moved back to the UK and became lecturer in the department of Bioengineering of Imperial College London (UK) where he is still currently working as a Reader in Biosensor Development. His research group is focusing on the design and development of molecular probes and devices for the detection of circulating cell-free nucleic acid biomarkers in liquid biopsies.Working in close collaboration with clinicians, Dr Ladame has a strong interest in translational research (early cancer diagnosis and prenatal testing) and has recently focused his research on the development of novel technologies that can be easily implemented in clinic to maximise impact on patients.
Page 16 Poster Presentations 1 Joseph Broomfield Poster Pages 18&19 2 Fariza Aina Abd Manan
Page 17 Handheld ISFET detection ofYAP1 and Androgen Receptor mRNA from clinical samples fro prostate cancer prognosis Joseph Broomfield Imperial College London, Department of Electrical and Electronic Engineering This work presents a handheld lab-on-chip device developed collaboratively between the Centre for Bio-Inspired Technology and the Androgen Signalling group at Imperial College London. Previ- ous work has validated a panel of circulating mRNA biomarkers for prostate cancer (PCa) prognostics using loop-mediated isothermal amplification (LAMP) and ion-sensitive field-effect transistors (IS- FETs). These developed assays can specifically and sensitively detect mRNA from prostate cancer cell lines. This work presents the validity of these assays for minimally invasive detection of RNA extracted from blood plasma. On account of the low abundance and lability of circulating mRNA, an extraction methodology for detection from the blood was optimised. Clinical blood plasma samples from PCa patients indicated that the LAMP assays were sufficient to detect circulating YAP1 and androgen receptor mRNA. Both of these markers are associated with prostate cancer tumour aggressiveness and detection was corroborated with qPCR. Implementation of the benchtop LAMP assays onto the Lab-on-Chip is currently ongoing including a multiplexed device for simultaneous detection of multiple PCa biomarkers. Aptamer Conjugated Chitosan-based Nanocarriers for PossibleTargetedTheranostic of Non-Muscle Bladder Cancer Fariza Aina Abd Manan 1, Nor Azah Yusof 1,2,*, Jaafar Abdullah1,2 1 Institute of Nanoscience and Nanotechnology, Universiti Putra Malaysia, UPM Serdang, Serdang 43400, Selangor, Malaysia; jafar@upm.edu.my 2 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, UPM Serdang, Serdang 43400, Selangor, Malaysia * Correspondence : azahy@upm.edu.my (N.A.Y.) Bladder cancer (BC) is the most common genitourinary cancer that cause mortality across the world. Non-muscle invasive bladder cancer (NMIBC) accounts approximately 75-80% of incident cases of bladder cancer. Intravesical chemotherapy is an integral to the treatment of NMIBC with excellent curative effects. However, this method suffers from non-specific biodistribution, insufficient drug concentration at the lesion site, low therapeutic indices, and intolerable cytotoxicity. In present work, intravesical aptamer conjugated targeted drug delivery system (TDDS) using chitosan-based nanocarriers with high encapsulation efficiency of Mitomycin C (MMC) have been developed to improve drug biocompatibility in cells and tissues, preserve drug stability, accelerate intracellular uptake, facilitate drug biodistribution to the targeted cancer cells or tissues for cancer theranostics.The conjugated aptamer used as targeting ligand to bind with overexpressed biomarker,Vascular endothelial growth factor receptor 1 (VEGFR1) on the surface of cancerous cells. Preliminarily, the molecular docking studies of aptamer with VEGFR1 protein exhibits the binding free energy (ΔG) -15.3 kcal/mol. Further, experimental analysis using Enzyme Linked Oligonucleotide Assay (ELONA) validates that aptamer has excellent binding affinity (KD) 375 nM towards VEGFR1 protein. Overall, the developed aptamer TDDS synergistically elucidates the underlying efficient delivery of MMC with excellent targeted towards localized cancer sites to curb NMIBC reoccurrence and progression when applied to the real-time disease treatment.
Page 18 Motivation: Liquid Biopsies Circulating nucleic acids in the blood of cancer patients Blood vessel mRNA ctDNA miRNA Liquid biopsies are minimally invasive and can detect biomarkers without the requirement for a traditional biospy. Circulating mRNA are labile biomarkers and could provide temporal information on tumour state. The androgen receptor (AR) is a major oncogenic driver of prostate cancer. YAP1 mRNA is a marker of EMT in multiple cancer types, and its levels are reduced in metastatic castration-resistant prostate cancer. [1] How are we detecting mRNA? LAMP and ISFETs Loop-mediated isothermal amplification (LAMP) is an amplification technique that can be performed at one temperature (60 - 65oC). During an amplification event (i,.e mRNA is present) protons are released for each new nucleotide addition. (1) dNTP + dsDNAn= dsDNAn+1+ PPi +H+ Ion-sensitive field-effect transistors (ISFETs) can detect the rate of pH change. [2] In combination, these techniques can be utilised as a handheld device where the biosensor output can be recorded using a mobile phone. [3,4] ISFET biosensor with LAMP reaction on the array surface References (1): Selth, L. A. et al. A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer. Oncogene 36, 24–34 (2017). (2): Moser, N., Rodriguez-Manzano, J., Lande, T. S. & Georgiou, P. A scalable ISFET sensing and memory array with sensor auto-calibration for on-chip realtime DNA detection. IEEE Transactions on Biomedical Circuits and Systems 12, 390–401 (2018). (3): Broomfield, J. et al. Handheld ISFET Lab-on-Chip Detection of TMPRSS2-ERG and AR mRNA for Prostate Cancer Prognostics. IEEE Sensors Letters 7, (2023). (4): Broomfield, J. et al. Detection of YAP1 and AR-V7 mRNA for Prostate Cancer Prognosis Using an ISFET Lab-On-Chip Platform. ACS Sensors 7, 3389– 3398 (2022). Handheld ISFET detection of YAP1 and Androgen Receptor mRNA from clinical samples for prostate cancer prognostics
Page 19 Joseph Broomfield 1,2, Melpomeni Kalofonou 1, Costanza Guilli 1, Sue M. Powell 2, Nick Moser 1, Stephen Mangar 2, Charlotte L. Bevan 2, Pantelis Georgiou 1. Benchtop detection of YAP1 and AR mRNA Handheld Lab-on-Chip detection RNA was extracted from blood plasma samples from prostate cancer patients and tested for YAP1 and AR expression with RT-pHLAMP. In each case, 12 out of 13 samples RT-pHLAMP detection agreed with results obtained by RT-qPCR. qPCR primers designed to cover the exact region of the fragment detected RT-pHLAMP additionally showed concordance with 12 out of 13 samples. First frame of the ISFET array 'Amplification curve' from the ISFET biosensor Preliminary data indicates the ISFET Lab-on-Chip can detect YAP1 mRNA in clinical samples. Sensor output rises during an amplification event when the target mRNA is present. Generation of a multiplex device for simultaneous detection of YAP1 mRNA and AR is ongoing. This works presents the foundation for simultaneous handheld detection of circulating mRNA for prostate cancer prognostics. Positive (top) and negative (below) sensor outputs The authors of this work would like to thank all members of the Bevan and Georgiou groups for their insights. This work was funded by a CRUK convergence PhD Scholarship. (1) Centre for BioInspired Technology, Electrical and Electronic Engineering, Imperial College London, SW2 7AZ. (2) Imperial Centre for translational and experimental medicine, Surgery and Cancer, Imperial College London, W12 0NN. Lacewing Handheld Device Acknowledgements
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