Combining the Strengths of Mid-IR and Raman Spectroscopies on Single Chip for Rapid Bedside Biomarker Diagnostics
Lead Research Organisation:
University of Southampton
Department Name: Optoelectronics Research Centre (ORC)
Abstract
There is a pressing need for diagnostic tools that can produce results quickly from patients' bedsides and in doctors' surgeries. Rapid, accurate results will allow rapid therapeutic decisions and save lives at reduced cost. In contrast, existing technologies require transfer of samples to centrally located laboratories equipped with sophisticated instruments, and highly skilled personnel.
Bedside diagnostics using simplified, compact, versatile and efficient tools providing analysis results within a few minutes will therefore be a boon for many critically ill patients. In this project, we propose to develop two-in-one attenuated total reflection (ATR)/Raman chips that are compact, mass-producible, affordable, reliable, user-friendly and highly sensitive. The availability of such chips will enable the full potential and complementary nature of mid-IR molecular fingerprint and Raman spectroscopies to be exploited for bedside point-of-care diagnosis of critically ill patients who require rapid therapeutic decisions, meeting the ASSURED criteria set by the World Health Organisation (WHO).
For example, provision of rapid diagnostic information will be invaluable for preterm infants (24-30 weeks gestation), for whom treatment decisions must be made as soon after birth as possible. Due to their lung immaturity, such infants are at high risk of suffering from neonatal Respiratory Distress Syndrome (nRDS), which has a high rates of mortality and morbidity with a major long-term economic burden on healthcare services. Using nRDS as an exemplar, we propose to develop a compact, versatile, rapid and easily operable bedside diagnostic tool for the next-generation bedside point-of-care to provide a predictive diagnostic test for nRDS to inform treatment options.
The diagnostic device platform proposed here combines the complementary capabilities of fingerprint Mid-IR and Raman spectroscopies, each of which has been shown independently to be powerful biodiagnostic tool for specific biomarkers. In addition, we will employ a unique signal enhancement strategy that will simultaneously benefit both IR and Raman spectroscopies and significantly enhance their sensitivities. This new photonic technology and the portable diagnostic device proposed will not only underpin next-generation biomedical diagnostic applications but will also have major impacts in environmental monitoring and sensing including water pollution monitoring and trace toxic gas sensing.
Bedside diagnostics using simplified, compact, versatile and efficient tools providing analysis results within a few minutes will therefore be a boon for many critically ill patients. In this project, we propose to develop two-in-one attenuated total reflection (ATR)/Raman chips that are compact, mass-producible, affordable, reliable, user-friendly and highly sensitive. The availability of such chips will enable the full potential and complementary nature of mid-IR molecular fingerprint and Raman spectroscopies to be exploited for bedside point-of-care diagnosis of critically ill patients who require rapid therapeutic decisions, meeting the ASSURED criteria set by the World Health Organisation (WHO).
For example, provision of rapid diagnostic information will be invaluable for preterm infants (24-30 weeks gestation), for whom treatment decisions must be made as soon after birth as possible. Due to their lung immaturity, such infants are at high risk of suffering from neonatal Respiratory Distress Syndrome (nRDS), which has a high rates of mortality and morbidity with a major long-term economic burden on healthcare services. Using nRDS as an exemplar, we propose to develop a compact, versatile, rapid and easily operable bedside diagnostic tool for the next-generation bedside point-of-care to provide a predictive diagnostic test for nRDS to inform treatment options.
The diagnostic device platform proposed here combines the complementary capabilities of fingerprint Mid-IR and Raman spectroscopies, each of which has been shown independently to be powerful biodiagnostic tool for specific biomarkers. In addition, we will employ a unique signal enhancement strategy that will simultaneously benefit both IR and Raman spectroscopies and significantly enhance their sensitivities. This new photonic technology and the portable diagnostic device proposed will not only underpin next-generation biomedical diagnostic applications but will also have major impacts in environmental monitoring and sensing including water pollution monitoring and trace toxic gas sensing.
Planned Impact
We propose to develop optical devices that are simple and low-cost that are ideal for performing combined mid-infrared (mid-IR) and Raman spectroscopies providing complementary information to identify and quantify biomarkers in a clinical environment, for rapid bedside biomedical diagnostics. These chips will be capable of near-instantaneous disease detection to advance a healthy society with reduced medical costs.
This research will offer economic impacts by creating industrial growth through the realisation of novel photonic devices (one of the key enabling technologies) and will also make societal impact by the provision of new clinical devices for the bedside point-of-care diagnosis, benefiting clinicians and general public. The bedside diagnosis of critically ill patients will enable rapid therapeutic decisions, saving lives, reducing the economic burden on healthcare services and creating a resilient nation.
We will conduct roadshows and outreach programmes in schools and hospitals and demonstrate the potential benefits of these photonic devices developed in this project for the next-generation bedside point-of-care diagnostics.
Working in collaboration with SIME Diagnostics Ltd we are in a position to enhance the UK's already strong position in the medical diagnostics sensors market. As the technologies mature during the project, we will explore further routes to commercialisation as the possibility of low-cost, mass produced systems becomes clear. To enable this, the protection and exploitation of the results are important and at Southampton we are well supported for this by the University's Research and Innovation Services (RIS). RIS have expertise in IP protection, the identification of potential users of research results, licensing, business planning and spin-outs.
This programme will be of great value to the next generation of research scientists and it provides excellent opportunities for training PhD/MSc students and postdoctoral researchers in a highly multidisciplinary environment in a field with great practical potential, coupled with state-of-the-art technologies. They will interact with staff from multiple disciplines, and meetings of the team will foster cross-disciplinary engagement and an understanding of translation from fundamental science to practical application, providing an excellent foundation for the research leaders of the future.
This research will offer economic impacts by creating industrial growth through the realisation of novel photonic devices (one of the key enabling technologies) and will also make societal impact by the provision of new clinical devices for the bedside point-of-care diagnosis, benefiting clinicians and general public. The bedside diagnosis of critically ill patients will enable rapid therapeutic decisions, saving lives, reducing the economic burden on healthcare services and creating a resilient nation.
We will conduct roadshows and outreach programmes in schools and hospitals and demonstrate the potential benefits of these photonic devices developed in this project for the next-generation bedside point-of-care diagnostics.
Working in collaboration with SIME Diagnostics Ltd we are in a position to enhance the UK's already strong position in the medical diagnostics sensors market. As the technologies mature during the project, we will explore further routes to commercialisation as the possibility of low-cost, mass produced systems becomes clear. To enable this, the protection and exploitation of the results are important and at Southampton we are well supported for this by the University's Research and Innovation Services (RIS). RIS have expertise in IP protection, the identification of potential users of research results, licensing, business planning and spin-outs.
This programme will be of great value to the next generation of research scientists and it provides excellent opportunities for training PhD/MSc students and postdoctoral researchers in a highly multidisciplinary environment in a field with great practical potential, coupled with state-of-the-art technologies. They will interact with staff from multiple disciplines, and meetings of the team will foster cross-disciplinary engagement and an understanding of translation from fundamental science to practical application, providing an excellent foundation for the research leaders of the future.
Publications
Vincent Veluthandath A
(2022)
CMOS compatible design of photonic nanojet
Veluthandath A
(2023)
Quantification of lung surfactant lipid (dipalmitoylphosphatidylcholine/sphingomyelin) ratio in binary liposomes using Raman spectroscopy
in Journal of Raman Spectroscopy
Veluthandath A
(2021)
Photonic Nanojet Generation Using Integrated Silicon Photonic Chip with Hemispherical Structures
in Photonics
Veluthandath A
(2021)
Design of photonic nanojets on a silicon chip
Senthil Murugan G
(2020)
Mid-IR Spectroscopy: On-chip Devices and Biodiagnostic Applications (Invited)
Anthony Postle
(2023)
Surfactant therapy in acute Covid-19
Description | Biomarker detection and concentration prediction from the spectroscopic data using machine learning have been developed. This will be useful for the biomedical diagnosis in a point of care setting, especially in a near-bedside. We have performed electromagnetic modelling of microstructured silicon surfaces to enhance the strength of spectroscopic signal and thereby increasing the signal to noise ratio to detect very low level of biomarkers present in a liquid sample. We have completed the fabrication of first generation of microstructured chips for on-chip spectroscopy and they showed enhanced performance compared to conventional Mid-Infrared spectroscopy. We have also shown using Raman spectroscopy that biomarkers in aqueous samples (for example body fluids) can be detected and quantified. |
Exploitation Route | When the chips are fully characterised and compact instrumentation to contain the chip and perform spectroscopy devised, they will be tested under clinical condition for performing bedside biomedical diagnostics. |
Sectors | Agriculture Food and Drink Chemicals Digital/Communication/Information Technologies (including Software) Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
URL | https://doi.org/10.3390/s22051744 |
Description | We have developed a cost-effective Si-based photonic chip for mid-infrared spectroscopy, facilitating rapid disease detection and reducing costs and resources required for healthcare services. Machine learning-assisted on-chip spectroscopy we developed enhances biomarker detection and concentration prediction, while correcting for background interference, improving detectability. These innovations enable bedside biomedical diagnostics, fostering economic growth in photonic device manufacturing and improving healthcare outcomes. We are currently pursuing patent protection and collaborating with our university hospital for clinical validation, aiming to advance point-of-care diagnostics, save lives, and alleviate healthcare burdens. This innovation also holds potential for spin-off ventures. |
First Year Of Impact | 2023 |
Sector | Healthcare,Manufacturing, including Industrial Biotechology |
Impact Types | Societal Economic |
Description | COVID-19: Aerosolized Surfactant Clinical Trial |
Amount | $1,298,313 (USD) |
Funding ID | INV-016631 |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 03/2020 |
End | 10/2020 |
Description | Mid-infrared frequency comb generation using integrated chalcogenide microring resonators for on-chip spectrometers |
Amount | £11,825 (GBP) |
Funding ID | IEC\NSFC\201068 |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2023 |
Title | "Quantification of lung surfactant lipid (Dipalmitoylphosphatidylcholine / sphingomyelin) ratio in binary liposomes using Raman spectroscopy" |
Description | This dataset supports the publication: 'Quantification of lung surfactant lipid (Dipalmitoylphosphatidylcholine / sphingomyelin) ratio in binary liposomes using Raman spectroscopy', Journal of Raman Spectroscopy Doi:https://doi.org/10.1002/jrs.6631 |
Type Of Material | Database/Collection of data |
Year Produced | 2023 |
Provided To Others? | Yes |
Impact | This dataset supports the publication: 'Quantification of lung surfactant lipid (Dipalmitoylphosphatidylcholine / sphingomyelin) ratio in binary liposomes using Raman spectroscopy', Journal of Raman Spectroscopy Doi:https://doi.org/10.1002/jrs.6631 The datasets are shared in .dat format. Fig3.dat contains the data used for generating Fig. 3, Fig4.dat contains the data used for generating Fig. 4, and Fig5a.dat and Fig5b.dat contain the data represented in Figure 5 |
URL | https://eprints.soton.ac.uk/485032/ |
Title | A simplified approach to correct atmospheric absorptions in Infrared Spectra |
Description | A simple method utilising just two sample spectra to correct the absorption bands of water vapour and CO2. |
Type Of Material | Computer model/algorithm |
Year Produced | 2024 |
Provided To Others? | No |
Impact | We developed an algorithm to correct for spectral interference by obtaining atmospheric contribution by subtracting two spectra. |
Title | Machine learning and chemometric analysis of spectroscopic data |
Description | We have developed a machine learning model to diagnose the neonatal Respiratory Distress Syndrome (nRDS) in prematurely born infants based on the biomarkers present in the amniotic fluid or gastric aspirates. We have proved that the model effectively predicts the condition using the Mid-IR spectroscopic data collected from the mixture of biomarkers. |
Type Of Material | Data analysis technique |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Currently there are no quick diagnosis method to detect this symptom and appropriately treating them. Our approach will provide a rapid point of care diagnosis at the bedside and not only save many lives but will also reduce the economic burden on health services by reducing the longtime morbidity due to improper therapeutic decisions (because of the lack of diagnosis techniques). |
URL | https://www.spiedigitallibrary.org/conference-proceedings-of-spie/11651/2578818/ATR-based-infrared-s... |
Title | Modeling parameters of Si hemispherical domes for photonic nanojet generation |
Description | This data set provide the parameters used to model the on chip photonic nanojet. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | In this work we have explored photonic nanojet generation in in Si platform, which have established so far because usually the photonic nanojets (PNJ) are useful only when the refractive of the material is less than 2- and Si has a refractive index of 3.4. We have studied the PNJ geration from Si hemispherical domes on Si substrate and established that the proposed design can overstep the refractive index limit and possible to use Si to generate photonic nanojets which opens up a wide field of applications including on-chip optical tweezers, opto-fluidics and focal plane arrays. |
URL | https://eprints.soton.ac.uk/452810 |
Title | Prediction of Neonatal Respiratory Distress Biomarker Concentration by Application of Machine Learning to Mid Infrared Spectra |
Description | Dataset to support article by Ahmed, W.; Veluthandath, A.V.; Rowe, D.J.; Madsen, J.; Clark, H.W.; Postle, A.D.; Wilkinson, J.S.; Murugan, G.S. Prediction of Neonatal Respiratory Distress Biomarker Concentration by Application of Machine Learning to Mid-Infrared Spectra. In "Sensors" 2022, 22, 1744. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | Currently there are no dataset available for training machine learning algorithms to detect the ratio of lung surfactants DPPC and SM. Different ratios of DPPC and SM where prepared in lab. FT-IR spectrum of the lung surfactant are meticulously collected and analyzed. Data provided is corrected for humidity level and will be helpful in training future algorithms. |
URL | https://eprints.soton.ac.uk/455045/ |
Title | Training data set for chemometric analysis lung surfactants using FT-IR spectroscopy |
Description | We have collected an extensive set of data consists of IR spectrum of lung surfactant with different DPPC and SM ratio to train the machine learning algorithm. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | Currently there are no dataset available for training machine learning algorithms to detect the ratio of lung surfactants DPPC and SM. Different ratios of DPPC and SM where prepared in lab. FT-IR spectrum of the lung surfactant are meticulously collected and analyzed. Data provided is corrected for humidity level and will be helpful in training future algorithms. |
URL | https://doi.org/10.5258/SOTON/D1829 |
Title | Training data set for chemometric analysis of lung surfactants using Raman spectroscopy |
Description | We are collecting an extensive set Raman spectrum of lung surfactant in lipid vesicles are solid form to train the spectrum of lung surfactant to train the machine learning algorithm. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | No |
Impact | Currently there are no dataset available for training machine learning algorithms to detect the ratio of lung surfactants DPPC and SM using Raman spectroscopy. We have prepared different ratios of DPPC and SM and Raman spectrum was collected and analyzed. Data provided is corrected for humidity level and will be helpful in training future algorithms. |
Description | Collaboration with IIT Madras (India) on the newly formed Centre of Excellence: Centre of Excellence on Advanced Biochemical Sensing and Imaging Technologies (ABSIT) |
Organisation | Indian Institute of Technology Madras |
Country | India |
Sector | Academic/University |
PI Contribution | Initiating collaborative research on biochemical sensing based on the photonic platform we are developing. |
Collaborator Contribution | The Centre of Excellence brought together a multidisciplinary team of experts from departments of Physics, Electrical Engineering, Chemistry, Biotechnology with similar research interests in Sensing and Imaging. Collaborating with this team of scientists and engineers, will provide us opportunity to flourish with complementary skills and achieve wider impacts on the biomedical diagnostics research. |
Impact | This is a multidisciplinary collaboration involving Physics, Electrical Engineering, Chemistry and Biotechnology. |
Start Year | 2020 |
Description | Collaboration with University Hospital Southampton |
Organisation | University Hospital Southampton NHS Foundation Trust |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | This collaboration was initiated as part of effort to extened the phtonic chips for diagnois of ARDs. |
Collaborator Contribution | Our partners will collect samples from patients. |
Impact | Working on the ethical statment |
Start Year | 2022 |
Description | SIME Diagnostics Limited (Collaborating Project Partner) |
Organisation | SIME Diagnostics Limited |
Country | United Kingdom |
Sector | Private |
PI Contribution | The sensing platform developed will be first patented and then commercial exploitation will be sought through this partner. |
Collaborator Contribution | This partner will help with the clinical application and commercialisation of the sensing platform |
Impact | Yes, Multidisciplinary involving Photonics, Nanotechnology, Artificial Intelligence and clinical point of care. |
Start Year | 2020 |
Description | 'Scientists in the garden' at Light Up trails, Hillier Gardens |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Our lab member has done outreach, 'Scientists in the garden' at Light Up trails, Hillier Gardens (December 2023), explaining key photonics concepts including reflection, spectra, and diffraction to people of all ages. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.lightuptrails.com/events/light-up-hillier-gardens |
Description | 'Women in Photonics' careers workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Ms Eleanor Osborn attended the 'Women in Photonics' careers workshop in Jena, Germany 26th-30th November 2023, which had a specific focus on biophotonics. She also presented a poster on this project and gained a valuable insight into potential career pathways in addition to growing my network. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.asp.uni-jena.de/events/women-in-photonics |
Description | Interview about project and my experience as a PhD student |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | For International Women's Day 2023, our PhD student, Eleanor Osborne was interviewed about her project and my experience as a PhD student by the department's events coordinator. This was used on ORC social media to celebrate International Women's Day and emphasise the importance of women in STEM. |
Year(s) Of Engagement Activity | 2023 |
Description | Interview for NIHR BRC Southampton News letter |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | BRC Southampton has published a brief interview featuring the the results related to this work. |
Year(s) Of Engagement Activity | 2024 |
URL | https://www.southamptonbrc.nihr.ac.uk/post/using-light-to-diagnose-lung-injury-meet-aneesh-vincent-v... |
Description | Lab tours and demonstrations |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Ms. Eleanor Osborne, intriduced students to working in science and introduced them to the experience with tours and demonstrations in our labs, including FTIR spectroscopy. |
Year(s) Of Engagement Activity | 2023 |
Description | Light Express laser show |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Ms. Eleanor Osborn, co-organised the University of Southampton's Light Express laser show, reaching approximately 1200 people during shows at the University's Science and Engineering Festival (March 18th 2023) and at a local secondary school (5th December 2023). |
Year(s) Of Engagement Activity | 2023 |
URL | http://www.lightexpress.soton.ac.uk/ |
Description | Light Express laser show on Scinence and engineering day. |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | The University of Southampton runs a yearly Science and Engineering Day on campus which invites the public to explore research conducted at the university through interactive workshops and talks. A member of our group volunteered on the Science and Engineering Day with the University's Light Express laser show (7th May 2022) and has helped to organise the show at this year's festival (18th March 2023) as part of their role as Equity, Diversity and Inclusion and Outreach Officer for the University of Southampton Optics and Photonics Society. The show runs for approximately 40minutes, during which time the audience learn some important concepts in optics and photonics such as total internal reflection, and how light is used in their daily lives (i.e. optical fibres for the internet). |
Year(s) Of Engagement Activity | 2022 |
Description | Light wave road show |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Research group member had helped run workshops on campus for Year 8 (12-13 year old) students based on spectroscopy as part of the University of Southampton's award-winning Light Wave program on 24th November 2022. Participants made spectroscopes from CDs and card, enabling them to identify the gases in different lamps (i.e. helium) from their component colours. This introduced the ideas of absorption and emission, from which some research projects using spectroscopy were discussed, including our own work on biomolecular detection. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.lightwave.soton.ac.uk/about |
Description | News about the project in national online magazines |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | The main purpose of this news release was to create awareness among common public and show the potentials of multidisciplinary research, especially the role of photonic devices in rapid biomedical diagnostics in point of care settings. During the national lockdown restrictions, we thought that this is the alternative to reach the common public with our idea. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.theengineer.co.uk/nrds-rapid-test-southampton/ |
Description | Optics workshops for the general public |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Undergraduate students |
Results and Impact | A number of workshops on optics were run for the general public as part of Southampton Festival for Arts and Humanities. Activities included making kaleidoscopes and spectroscopes with a range of age groups from primary school to adults. Those attending gained an understanding of reflection and refraction, and how optical fibre communications work. These activities were also used to help explain some of the photonics research being carried out at the University of Southampton. |
Year(s) Of Engagement Activity | 2021 |
Description | Workshops at the University of Southampton |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Ms. Eleanor Osborne help run a workshops at the university (18th November 2023) explaining key photonics concepts including reflection, spectra, and diffraction to people of all ages. |
Year(s) Of Engagement Activity | 2023 |