The Multicorder

Lead Research Organisation: University of Glasgow
Department Name: School of Engineering

Abstract

We propose to create the world's first broad spectrum sensor technology - the Multi-Corder. We will do this by exploiting and advancing leading-edge microelectronic engineering. The world of electronics is dominated by complementary metal oxide semiconductor (CMOS) technology. CMOS has made modern computing and communications possible and has also made an enormous impact on sensing technology such as the digital camera chip. Most recently CMOS has enable the development of the personal genome machine - a next generation sequencing system. We propose to create technology to sense the personal metabolome. This is important since where the genome may indicate an individual's propensity towards a disease, the metabalome is an immediate measurement of body function, hence provides a means of diagnose. Not all possible afflictions are measurable using the metabalome. Using the same fundamental technology we also propose to detect microbial infectious agents. Bacterial affliction already in the body, or in the environment (e.g. a hospital ward) will be targetted, alleviating major problems such as hospital acquired infection. Further beneficiaries are in point of use diagnostic tools and highly portable systems capable of use in the developing world where there is limited infrastructural support.
We also foresee yet more ambitious outcomes from the research, and we expect to made progress towards their realisation. We envisage that once a full measurement and analysis of a patient or a contaminated area is achieved, the Multi-Corder technology will underpin new methods of chemical synthesis for drugs. We will demonstrate the use of the technology for direct, high-speed, visualisation of chemical activity, and the means by which the data can be used to control the chemical process required for synthesis.
The targets that we will address will take advantage of the ability of microelectronics to make many (millions if needs be) of devices on a single chip, or to integrate diverse technologies together. The core semiconductor technology will be augmented by chemical, lithographic and bio-technologies in order to build complex functions. Our approach is based on a combination of established track record, new insights, and emergent technologies for which we have established trial feasibility. Using our current knowledge as a springboard, we will exploit the flexibility and collaborative framework that a Programme Grant will afford us to create an exciting new technology.

Planned Impact

We propose to create a technology platform to visualise chemical processes in situ, investigate the personal metabolome, identify infectious agents and, from these data, work towards controlled synthesis of targeted therapeutics locally and autonomously. The heart of this ambitious system will be an integrated circuit containing many detectors, each of which is capable of functionalisation to make a Multi-Corder. Our research programme marries investigator track records and established feasibility, through early stage outputs, to a research vision with far-reaching, long-term, aims.
This programme will impact upon the capacity of semiconductor technologies and the expansion of their use, through design and application, into new markets. Through computer and communications technologies microelectronics has revolutionised every facet of our lives, and we will show that there is potential for much more to come. There will be new impacts on medical diagnostics, environmental sensing, food and drink quality control, analytical tools for chemical and biological sciences, and control of synthesis technologies. Stimulated by such possibilities, and driven by our expertise in Information and Communications Technology (ICT) and Micro-Nano Technology (MNT), the research team in this Programme Grant application will strive to develop new, open, integrated architectures leading to widespread use in many settings, from the clinic to the field. The knowledge generation will be cross-disciplinary, with each subject area exposing new scientists within their field to the power of interdisciplinary research. Specific impacts will occur upon patients, infection control professionals, UK industry, the wider community and the developing world.
The proposers are engaged with government and non-governmental agencies to provide advice and leadership. They have also worked extensively in knowledge transfer and have successfully seen their research commercialised. The team will therefore build on its track record to ensure the research achieves the best possible outcomes.
Traditional mechanisms for scientific dissemination remain the gold-standard for scientific quality assessment. We will publish our research in the leading scientific and technical peer-review journals. We will continue to accept invitations to present our work at international conferences, and we will support and encourage our post-doctoral researchers and PhD students to write and present papers at leading conferences and workshops, obtaining a two-fold impact of introducing new science and scientists to the international community. In addition to communication with our peers, we have, as a team, an excellent record of scientific engagement with the lay community of science funders and end-users. We will continue this work through the learned societies, and with the help of university corporate communications who have successfully engaged the interest of broadcast and print media.

Publications

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Accarino C (2020) Noise characteristics with CMOS sensor array scaling in Measurement

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Al-Rawhani MA (2020) Multimodal Integrated Sensor Platform for Rapid Biomarker Detection. in IEEE transactions on bio-medical engineering

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Anamimoghadam O (2015) Electronically Stabilized Nonplanar Phenalenyl Radical and Its Planar Isomer. in Journal of the American Chemical Society

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Caramelli D (2018) Networking chemical robots for reaction multitasking. in Nature communications

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Cheah B (2017) Metabolomics on Integrated Circuit in Procedia Technology

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Cheah BC (2016) An Integrated Circuit for Chip-Based Analysis of Enzyme Kinetics and Metabolite Quantification. in IEEE transactions on biomedical circuits and systems

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Duros V (2017) Human versus Robots in the Discovery and Crystallization of Gigantic Polyoxometalates. in Angewandte Chemie (International ed. in English)

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Giagkoulovits C (2018) A 16 x 16 CMOS Amperometric Microelectrode Array for Simultaneous Electrochemical Measurements in IEEE Transactions on Circuits and Systems I: Regular Papers

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Gromski P (2019) How to explore chemical space using algorithms and automation in Nature Reviews Chemistry

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Sartzi H (2015) Trapping the d Isomer of the Polyoxometalate-Based Keggin Cluster with a Tripodal Ligand. in Angewandte Chemie (International ed. in English)

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Shakoor A (2018) CMOS Nanophotonic Sensor With Integrated Readout System in IEEE Sensors Journal

 
Description Multimodal sensors on integrated circuits
Enzyme based assays
Ion sensors
Integration technologies
Immunoassays
Exploitation Route We have formed a new company called Multicorder DX and we are now in discussion with several potential investors. A CEO designate has been appointed.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://www.multicorderdx.co.uk
 
Description 2 patents have been filed and are now at international stage. A company has been formed called Multicorder DX and we are actively seeking investment.
First Year Of Impact 2019
Sector Agriculture, Food and Drink,Electronics,Healthcare
Impact Types Societal,Economic

 
Description Scottish Funding Council review of Research Pooling
Geographic Reach National 
Policy Influence Type Participation in a national consultation
URL https://www.universities-scotland.ac.uk/briefing-evidence/independent-review-scottish-funding-counci...
 
Description EPSRC Programme Grant
Amount £3,400,000 (GBP)
Funding ID EP/K021966/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 10/2013 
End 09/2017
 
Title 1D silicon nitride grating refractive index sensor suitable for integration with CMOS detectors 
Description  
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
 
Title Hybrid Amperometric and Potentiometric Sensing Based on a CMOS ISFET Array 
Description  
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Hybrid localized surface plasmon resonance and quartz crystal microbalance sensor for label free biosensing 
Description  
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
 
Title Immunoassay Multiplexing on a Complementary Metal Oxide Semiconductor Photodiode Array 
Description Images and data captured by the CMOS photodiode array and subsequent calculations as a result of immunoassay experiments. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Plasmonic Gold Nanodiscs using Piezoelectric Substrate Birefringence for Liquid Sensing 
Description  
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
 
Title Plasmonic sensor monolithically integrated with a CMOS photodiode 
Description  
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
 
Description Leonardo (Diagnostics) 
Organisation Selex ES
Department SELEX Sensors and Airborne Systems
Country United Kingdom 
Sector Private 
PI Contribution regular meeting, project IAB, joint grant applications
Collaborator Contribution Partnership, meetings, invitations to company, research collaboration, networking
Impact Actively pursuing new EU funding opportunities. Strategic development ongoing.
Start Year 2013
 
Title Licence(s) pending (Final Report data) 
Description we have designed a novel integrated circuit with an array of sensors for which we have obtained design rights. 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2016
Licensed No
Impact We have not licenced the design to anyone, but aspects of the design are of interest to IHP, Germany.
 
Title METABOLITE DETECTION APPARATUS AND CORRESPONDING DETECTION METHOD 
Description A CMOS-based chip having multiple sensing modalities that are able independently to detect multiple metabolites (for example cholesterol and glucose) present in a sample. In particular, the chip provides multiple sensing modalities capable of performing detection within the same physical test volume, i.e. the chip can simultaneously detect a plurality of chemical reactions occurring in the test volume, where each chemical reaction yields a result that is independently detectable. The chip may comprise an optical sensor (e.g. photodiode) and a chemical sensor (e.g. pH sensor, embodied as an ISFET). With this technique, multiple metabolites may be measured in real time using a small scale point-of-care device. 
IP Reference WO2018215553 
Protection Patent application published
Year Protection Granted 2018
Licensed No
Impact Collaboration with Leonardo and Maddison
 
Title METABOLITE DETECTION APPARATUS AND METHOD OF DETECTING METABOLITES 
Description A CMOS-based chip having one or more sensing modalities that are able independently to detect multiple metabolites present in a biological sample. The multiple sensing modalities may be provided at different locations with respect to the chip, whereby the chip can simultaneously detect a plurality of metabolites by measuring behaviour of a test material in the different locations. The chip may utilise paper as a transport mechanism for the sample. The paper either conveys the sample to the different locations or itself provides discrete testing zones in which different metabolites can be independently detected. With this technique, multiple metabolites may be measured in real time using a small scale point-of-care device. 
IP Reference WO2018215554 
Protection Patent application published
Year Protection Granted 2018
Licensed No
Impact Collaboration with Leonardo and Maddison
 
Description New Statesman Shakespeareomics 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article outlining scientific approaches, especially using "omics" technology to learn about the life and work of William Shakespeare
Year(s) Of Engagement Activity 2016
URL https://www.newstatesman.com/science-tech/2016/01/shakespeareomics-how-scientists-are-unlocking-secr...
 
Description Press announcement of major publication that received significant attention in the news media 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A Star Trek-inspired handheld device based on a silicon chip could help make rapid, sophisticated medical diagnostics more accessible to people around the world, scientists say.

In a new paper published in the journal Biosensors and Bioelectronics, researchers from the University of Glasgow describe the latest development in their 'multicorder' project, inspired by Star Trek's famous tricorder device, which the show's medics use to make quick and accurate diagnoses.
Multicorder

Their new device, which pairs a handheld sensor with a smartphone app, measures the levels of various metabolites in fluid samples from patients.

Metabolites are small molecules found in fluids from the human body. By measuring and monitoring their relative abundance, scientists can keep track of general heath or the progression of specific diseases.

The ability to rapidly detect and quantify multiple metabolite biomarkers simultaneously makes this device particularly useful in cases of heart attack, cancer and stroke, where rapid diagnosis is vital for effective treatment.

While metabolites can currently be measured by existing processes such as nuclear magnetic resonance and hyphenated mass spectrometry techniques, both approaches are expensive and require bulky equipment which can be slow to offer diagnostic results.

The researchers' new device is built around a new form of complementary metal oxide semiconductor (CMOS) chip. CMOS chips are inexpensive to produce and are often used in imaging devices.

The chip is smaller than a fingertip and is divided into multiple reaction zones to detect and quantify four metabolites simultaneously from body fluid such as serum or urine. The device can be operated via any Android-based tablet or smartphone which provides data acquisition, computation, visualisation and power.
Multicorder

Dr Samadhan Patil of the University of Glasgow's School of Engineering is lead author on the paper. Dr Patil said: "We have been able to detect and measure multiple metabolites associated with myocardial infarction, or heart attack, and prostate cancer simultaneously using this device. This device has potential to track progression of the disease in its early phase and is ideally suited for the subsequent prognosis".

Professor David Cumming, Principal Investigator of the project from University's School of Engineering said: "Handheld, inexpensive diagnostic devices capable of accurately measuring metabolites open up a wide range of applications for medicine, and with this latest development we've taken an important step closer to bringing such a device to market."

"It's an exciting breakthrough and we're keen to continue building on the technology we've developed so far."

Professor Mike Barrett of the University's School of Life Sciences, co-investigator of the project, said: "This new handheld device offers democratisation of metabolomics, which is otherwise confined within the laboratory, and offers low cost alternative to study complex pathways in different diseases".

The paper, titled 'An integrated portable system for single chip simultaneous measurement of multiple disease associated metabolites', is published in Biosensors and Bioelectronics.

The project was supported by funding from the Engineering and Physical Sciences Research Council (EPSRC).
Year(s) Of Engagement Activity 2018
URL https://www.gla.ac.uk/news/archiveofnews/2018/september/headline_613716_en.html