LCVD: Low-cost Cell-extract Viral Diagnostics

Lead Research Organisation: University of Cambridge
Department Name: Pathology

Abstract

Virus disease burden in South Africa
South Africa has one of the highest rates of HIV infection worldwide. For infected individuals, drug therapy depends on knowing their virus load (VL) that is, how much virus is in circulation. About 2.4 million HIV VL tests costing $25 to $40 each, were performed last year in SA but the test is still unavailable those without access to major health care centres. Human norovirus (HuNoV; "winter vomiting virus") is highly infectious and responsible for 90% of non-bacterial diarrheal disease and studies in sub-Saharan Africa suggest that a significant proportion of diarrhea-related deaths in children under 5 go unreported. Thus it is likely that HuNoV infection is an underestimated health threat in SA. Addressing both of these problems with low cost point-of care diagnostic tests would greatly improve diagnosis and treatment, reducing mortality and also the heavy economic burden these diseases.

Aims and goals of the proposal
Our ultimate aim is to co-develop methods to rapidly design and construct cost-effective point-of-care diagnostics for infectious disease agents responsible for high morbidity and mortality in South Africa and other low-income regions. We will target HIV virus load (VL) testing and human norovirus (HuNoV) diagnosis. Recently, biologically-based "biosensor" tests for Zika virus and Ebola virus have been developed that can be produced on paper strips. These tests have the potential to be very low cost because they use a soup or extract from cells to identify the virus. The "cell-free" extract can be spotted onto paper strips, which allows a type of "dipstick" biosensor test for the virus. We plan to refine this basic process by having a team of UK and SA researchers co-develop the cell-free biosensors for HIV and HuNoV. The co-development will both train SA researchers in method development but also allow the method to be taught to other researchers that can then apply the method to their own research. Hence, we aim to co-develop a sustainable technology for SA and other low-income areas. Our goals are:
1) to produce prototype low cost point-of-care diagnostic tests for HIV VL testing and HuNoV diagnosis
2) to use the co-development research process to generate a set of cell-free biosensor methods as a platform technology accessible to SA and other LMIC researcher and educators
3) to use the co-development research process to broadly train individual researchers (our research team) and teach the methods and train other researchers in SA. Our proposal is based on co-development of cell-free in vitro biosensor diagnostics using our research teamwork to drive innovation and integration of laboratories and personnel in the UK and South Africa.

Planned Impact

This project aims to produce prototype Point-of-Care cell-free paper based diagnostics for HIV Viral Load and Human Norovirus detection. The goal is to produce low-cost paper based sensors capable of accurately diagnosing HuNoV and reporting HIV viral load that have low equipment/infrastructure requirements such that they can be easily accessible and distributable in an LMIC setting.

Due to this, direct beneficiaries would include all LMIC's that would benefit from low-cost low-infrastructure compatible diagnostics for these two pathogens, and the list of these is fairly large, particularly in the African continent. This would benefit health organisations through lower costs, health professionals from faster turnaround and patients through increased accessibility.

The project includes extensive collaboration between UK and South African partners to both develop the prototype and build capacity locally in South Africa such that further biosensors can be developed in the future. The sensor being developed is essentially a platform technology that can be readily adapted to detection of other pathogens and environmental contaminants. This fact, combined with the knowledge transfer and infrastructural capacity enhancement coming from this project to the South African collaborators means that at the end of the granting period they will have the skills and equipment to develop further sensors suiting their needs in other areas.

Workshops and training events held by the team during the granting period will also serve to further disseminate the underlying principles of cell-free paper based biosensor technologies to the wider area. This will help engage the wider academic community in South Africa and other countries in the region and enhance their ability to further develop these technologies to suit their own needs.

The product development and capacity building resulting from this project will also mean that manufacture of the end product could take place in South Africa, providing high-skill jobs and potentially significant revenues which will serve to boost the local economy.

Publications

10 25 50

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Guzman-Chavez F (2022) Constructing Cell-Free Expression Systems for Low-Cost Access in ACS Synthetic Biology

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Gil Rosa B (2022) Multiplexed immunosensors for point-of-care diagnostic applications. in Biosensors & bioelectronics

 
Description LCVD is a grant aimed at developing diagnostic tests for key virus-borne disease. For infected individuals, drug therapy depends on knowing their virus load (VL) that is, how much virus is in circulation. For example, bout 2.4 million HIV VL tests costing $25 to $40 each, were performed last year in SA but the test is still unavailable those without access to major health care centres. South Africa (SA) has one of the highest rates of HIV infection worldwide. For infected individuals, drug therapy depends on knowing their virus load (VL) that is, how much virus is in circulation. About 2.4 million HIV VL tests costing $25 to $40 each, were performed last year in SA but the test is still unavailable those without access to major health care centres. We employed techniques from synthetic biology to do R&D to produce prototype diagnostics tests for HIV and for Hepatitis B (For a number of reasons, it was not deemed feasible to continue with Human Norovirus) so we have developed prototypes for HIV diagnostics, expanding our work to Hepatitis B and to Typhoid, both diseases having exceptionally high incidence rates in SA:

-Development of a testing pipeline to screen CRISPR Cas 12 assay designs: We developed an automated testing workflow to screen different combination of assay condition to identify the assays with the best diagnostic performance for Hepatitis B Virus. This involved combining isothermal amplification technologies with Cas 12 in a way that maximised the performance of each element. On top of this the assays were made in a modular manner and were lyophilised and able to work with mass-producible lateral flow designs.-

-Testing assay designs on clinical samples: Our research partners in South Africa were given the details of optimised assay and were able to achieve similar performance. They were then able to start testing the assay on Hepatitis B Virus clinical isolates to characterise performance on real world samples.

-Running workshop in South Africa (1-14 July 2019): A team of academics gave seminars and hands on demos to a cohort of African researcher on emerging technologies such as CRISPR Cas 12 and isothermal amplification techniques. Crucially this capacity-building through workshops and through developing educational guides, will enable local scientists in South Africa and elsewhere to carry on after the LCVD prototypes to design and build their own synthetic biology diagnostics.

-Along with these achievements, platform technologies from this project were used in NHS efforts in the Covid-19 pandemic (see Narrative Impact).
Exploitation Route The prototype diagnostics could be taken forward into further research and development for practical and commercial use as devices.

The wealth of educational materials that we have developed can be used by scientists in LMICs to develop their own prototypes

Our platforms can be scaled up for use in national campaigns as was demonstrated during the pandemic (see Narrative Impacts)
Sectors Education,Healthcare,Government, Democracy and Justice,Pharmaceuticals and Medical Biotechnology

 
Description The COVID-19 pandemic was an unprecedented time for researchers throughout the UK, with many forced to work from home for the duration of the lockdown periods. However, the nature of the LCVD project meant that we were perfectly poised to contribute and we were able to pivot our own research to target the challenges faced by the National Health Service. During early 2020 the NHS was under pressure, with very limited SARS-CoV-2 testing capacity. Imperial College worked closely with NHS colleagues at North West London Pathology to validate a SARS-CoV-2 testing platform that currently performs the majority of SARS-CoV-2 testing in North West London. Imperial College also collaborated with colleagues within the university to launch an Imperial College DHSC funded Lighthouse laboratory (and student and staff testing service). Both of these testing services are still running (with the Imperial College lighthouse lab scaled back to perform only staff and student testing) and have performed in excess of 1.5 million SARS-CoV-2 tests to date. Links: https://ukdri.ac.uk/news-and-events/team-behind-robotic-covid-19-testing-platform-publish-new-workflow-details-and-two-rapid-assays-to-help-others-scale-up-testing-efforts https://ukdri.ac.uk/news-and-events/robotic-coronavirus-testing-platform-developed-by-uk-dri-researchers-set-to-significantly-increase-uk-testing-capacity https://www.imperial.ac.uk/news/214173/imperials-covid19-testing-goes-live/ https://www.medcityhq.com/2021/02/25/setting-up-the-new-covid-testing-lab-at-imperial/ https://www.standard.co.uk/news/health/london-labs-give-boost-to-underfire-tracing-system-a4567496.html https://www.gov.uk/government/news/500000-daily-testing-capacity-reached-in-ongoing-drive-to-boost-test-and-trace https://www.imperial.nhs.uk/about-us/news/more-than-500-000-covid-19-tests-processed-by-nwlp https://bioengineeringcommunity.nature.com/posts/rapid-prototyping-and-validation-of-sars-cov-2-clinical-diagnostic-workflows https://thebiologist.rsb.org.uk/biologist-covid-19/covid-19-q-as-professor-paul-freemont
First Year Of Impact 2020
Sector Communities and Social Services/Policy,Healthcare,Government, Democracy and Justice,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Policy & public services

 
Description Chair, Diagnostics Subgroup of UN Technology Access Partnership
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a guidance/advisory committee
URL https://techaccesspartnership.net/
 
Description Fellow of World Economic Forum Global Futures Council on Synthetic Biology
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a guidance/advisory committee
URL https://www.weforum.org/communities/gfc-on-synthetic-biology
 
Description 2020 Research Development Programme (RDP)
Amount R100,000 (ZAR)
Organisation University of Pretoria 
Sector Academic/University
Country South Africa
Start 01/2020 
End 12/2021
 
Description AMPlify: redistributed manufacturing of antimicrobial peptides for wound care
Amount £68,622 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2021 
End 09/2021
 
Description Biomaker Africa Network (GCRF QR 2018-9 Pump Priming Fund)
Amount £80,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 01/2019 
End 08/2019
 
Description COVID-19 diagnostics for Africa
Amount € 499,933 (EUR)
Funding ID RIA2020EF-2918 
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country Netherlands
Start 10/2020 
End 01/2021
 
Description Equipping the Next Generation of INnovative biological Engineers to develop disease diagnostics for Africa (BioENGINE Africa STAR)
Amount £94,850 (GBP)
Funding ID BB/T01735X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 06/2020 
End 03/2022
 
Description GCRF Pump-priming Fund
Amount £80,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 12/2018 
End 07/2019
 
Description Health effects of a large scale drinking water intervention on arsenic levels in Goalmari, Bangladesh
Amount £79,000 (GBP)
Funding ID RG100049 
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 02/2019 
End 07/2019
 
Description Open microreactors for large scale manufacture
Amount £12,500 (GBP)
Organisation United Kingdom Research and Innovation 
Department Global Challenges Research Fund
Sector Public
Country United Kingdom
Start 06/2020 
End 05/2021
 
Description Paths to local manufacturing of affordable diagnostics in LMICs: a roadmapping approach
Amount £20,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 01/2021 
End 03/2021
 
Description Scaling up COVID-19 testing through open science hardware and local manufacturing
Amount £20,000 (GBP)
Organisation Cambridge-Africa Alborada Trust 
Sector Academic/University
Country United Kingdom
Start 05/2020 
End 05/2021
 
Description Spores against SARS-CoV-2
Amount € 110,000 (EUR)
Organisation Volkswagen Foundation 
Sector Charity/Non Profit
Country Germany
Start 01/2021 
End 06/2022
 
Description Synthetic Biology Strategic Research Initiative 2016-2019
Amount £165,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description Translating Cambridge Synthetic Biology to impact LMIC bioeconomies
Amount £166,886 (GBP)
Organisation University of Cambridge 
Department Isaac Newton Trust
Sector Academic/University
Country United Kingdom
Start 03/2021 
End 06/2024
 
Title Molecular Diagnostics Toolkit 
Description Enzymes are the heart of each and every diagnostic test. Enzymes are the means we can track, study and defeat old and new infectious diseases. However, enzymes are globally distributed from centralized foundries and, most often, require a cold chain for stability restricting their access to the many, even more in times of supply chain disruptions like is happening in the current COVID-19 pandemic. The Molecular Diagnostics Toolkit includes: 1) IPTG inducible, T7 promoter driven ready-to-use expression cassettes to produce essential enzymes used in diagnostic among which RT, Bst-LF, RPA enzymes, RNA inhibitors. Enzymes are His-tagged and cassettes design are based on literature and experimental evidence 2) A set of constructs for the production of Sars-CoV-2 RNA positive and negative controls 
Type Of Material Biological samples 
Year Produced 2020 
Provided To Others? Yes  
Impact The Molecular Diagnostics Toolkit has been distributed to > 40 researchers in >20 countries as of Feb 2021 and is being used for locally funded projects to manufacture enzyme for research and diagnostics in Chile, Peru, Argentina, Cameroon, Ethiopia and beyond. Impact will be tracked during 2021. 
URL https://stanford.freegenes.org/collections/open-genes/products/open-enzymes-diagnostic-collection#de...
 
Title OpenMTA 
Description Introduction of a new MTA, the Open Material Transfer Agreement (OpenMTA), that relaxes restrictions on the redistribution and commercial use of biomaterials while maintaining aspects of standard MTAs that support widespread adoption (for example, incorporation into semiautomated administration systems). In developing the OpenMTA, our motivation was to realize a simple, standardized legal tool for sharing biological materials as broadly as possible without undue restrictions, while respecting the rights of creators and promoting safe practices and responsible research. Importantly, we wanted the tool to work within the practical realities of technology transfer and to be sufficiently flexible to accommodate the needs of many groups globally (for example, providing support for international transfers and compatibility with public and philanthropic funding policies). 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact We are seeing increasing adoption of this OpenMTA for public distribution of materials, now adopted by twenty academic reseach institutions, and a similar number of companies. Being adopted by Addgene as a major international partner. 
URL https://www.openplant.org/openmta/
 
Title Configurable low-cost colorimetric reader test set-up development datasets 
Description The datasets in this item contain measurements performed using a configurable colorimetric readout set-up for automated readout from lateral flow test strips. The readout set-up consists of a 3D-printed enclosure device with detector module electronics contained inside, along with a mechanism into which a lateral flow test strip can be inserted. The set-up can be adjusted in x, y and z directions to allow for accurate positioning, alignment and optimization of measurements performed on both model and real lateral flow test strips. Lateral flow test strips can be analysed both without a cartridge housing or within a cartridge housing. The dataset contains the raw measurements and results of the data obtained from the generic test set-up for various configurations of test set-up and the lateral flow test strips analysed. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact The development of this research dataset enabled a compact and optimized prototype low-cost reader device to be realized. These developments were also submitted to the IEEE NANO 2021 international conference as part of an invited talk as well as a full conference paper. 
URL https://figshare.com/s/24ad0a2c7e1540c4e83d
 
Title Low-cost, packaged and wireless colorimetric reader for resource-limited point-of-care development datasets 
Description This dataset encompasses various datasets and results obtained during the Dr.-Ing degree entitled: Wireless colorimetric readout for resource-limited point-of-care. The work details a hybrid printed and packaged low-cost wireless color detector device. By combining the growing fields of paper-based diagnostics and printed electronics with Southern African clinic perspectives, a scalable, low cost, paper-based solution for result readout and communication was developed. Printed radio frequency identification devices with sensing capabilities were manufactured onto different low-cost and paper-based substrates to assess the practical functionality of these devices. Extensive images and results pertaining to this are included in this dataset. This work was further extended to target colour detection from lateral flow test strip devices and other typical paper-based rapid test formats. The results were compared to those obtained from manual readout using colour charts, a commercial lateral flow test strip reader and image analysis using ImageJ. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact These developments formed part of the Dr.-Ing degree of Dr Suzanne Smith, and resulted in several journal and conference paper publications. A patent was filed based on this work, demonstrating the potential future impact of these novel developments. Initial user testing of the devices shows promise for use as a tool in future developments towards effective point-of-care diagnostic solutions. 
URL https://figshare.com/s/32d18b29f78098b97aa3
 
Description Collaboration around Developing Diagnostics Workflows with North West London Pathology (NHS Diagnostic Lab) 
Organisation Imperial College Healthcare NHS Trust
Country United Kingdom 
Sector Hospitals 
PI Contribution We developed a SARS-CoV-2 RT-PCR diagnostic workflow from scratch that is being used for frontline diagnostic testing (pillar 1). We are also in the process of developing other diagnostic workflows that will directly impact on patient care in relation to SARS-CoV-2 infection and other infectious diseases.
Collaborator Contribution Obtained UKAS accreditation of the diagnostic workflow and worked together with Imperial College to train staff and run the workflow autonomously.
Impact Imperial College Lighthouse Laboratory RCPath Awards 2020: Significant Contribution to Specialty Multidisciplinary: Clinical, Operational and Scientific
Start Year 2020
 
Description Creating ultra-low-cost RNA sensors using in-house cell-free preparations 
Organisation Pontifical Catholic University of Chile
Country Chile 
Sector Academic/University 
PI Contribution We are optimizing drying protocols for cell-free systems (using a low-cost energy source) evaluating the stability of these samples after a shelf time and a transatlantic shipment. The outcome of this work will be directly used in our workshop 2020 at South Africa.
Collaborator Contribution They have designed toehold RNA sensors that can be programmed in house low-cost cell-free gene expression systems. We will use these results in our workshop 2020 at South Africa. Likewise, they will participate as speakers/ trainers in this workshop.
Impact A publication, "Ultra-low-cost RNA sensors using in-house cell-free preparations" (in preparation).
Start Year 2019
 
Description HIV and Hepatitis B Patient Sample Access in the UK 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution I and my research team will be contributing towards developing a Hepatitis B biosensor for use at the point of care. The Clinician involved (Professor Graham Cooke) is heavily involved with Hepatitis research in the UK and would profit from the development of a low cost diagnostic test.
Collaborator Contribution The Clinician is enabling our research team to access HIV viral load patient samples in the UK (and potentially Hepatitis B samples as well).
Impact None as of yet. We expect to begin testing patient samples by the end of the year.
Start Year 2018
 
Description Hepatitis B clinical sample access in South Africa 
Organisation National Institute for Communicable Diseases
Country South Africa 
Sector Public 
PI Contribution Our research team will be contributing towards the development of a low-cost, point-of-care (POC) test for Hepatitis B virus (HBV) detection and viral load quantification. The medical scientist with whom we have established a collaboration (Dr Nishi Prabdial-Sing) is the laboratory manager of the Hepatitis division at the National Institute for Communicable Diseases (NICD), South Africa. Dr Prabdial-Sing is also currently involved as a principal investigator in studies validating point-of-care tests for HBV and HCV viral load on patients attending the Liver clinic at Charlotte Maxeke hospital in Johannesburg.
Collaborator Contribution Dr Prabdial-Sing will provide our research team with Hepatitis B clinical samples in South Africa.
Impact None to date. We anticipate that clinical sample testing will begin by the end of the current year.
Start Year 2019
 
Description Hepatitis B clinical sample access in South Africa 
Organisation University of Pretoria
Country South Africa 
Sector Academic/University 
PI Contribution Our research team will be contributing towards the development of a low-cost, point-of-care (POC) test for Hepatitis B virus (HBV) detection and viral load quantification. The medical scientist with whom we have established a collaboration (Dr Nishi Prabdial-Sing) is the laboratory manager of the Hepatitis division at the National Institute for Communicable Diseases (NICD), South Africa. Dr Prabdial-Sing is also currently involved as a principal investigator in studies validating point-of-care tests for HBV and HCV viral load on patients attending the Liver clinic at Charlotte Maxeke hospital in Johannesburg.
Collaborator Contribution Dr Prabdial-Sing will provide our research team with Hepatitis B clinical samples in South Africa.
Impact None to date. We anticipate that clinical sample testing will begin by the end of the current year.
Start Year 2019
 
Description Riffyn 
Organisation Riffyn
Country United States 
Sector Private 
PI Contribution Introduction of Riffyn at Imperial College to training fellow researchers to use the software platform.
Collaborator Contribution Training of individuals to use the Riffyn software platform for experimental design, machine learning and data analysis. Continued support and advice on how to get the best out of the platform. Experimental and assay design advice.
Impact Training of Michael Crone in Oakland USA (January 2020) Training and introduction of Riffyn at Imperial and the London BioFoundry (Ongoing 2020)
Start Year 2020
 
Title Medical testing device and a manufacturing method therefor 
Description The invention relates to a medical testing device for capturing results from a microfluidic-based diagnostic test. The invention also relates to methods of manufacturing and preparing the medical testing device, as well as a method of capturing a diagnostic result from a microfluidic-based diagnostic test. The device includes: - a substrate which is foldable/bendable about one or more fold/bend lines; - an electronic circuit which is at least partially printed onto the substrate; and - a detection arrangement, wherein the device forms/defines a cavity/recess, when the substrate is bended or folded about the one or more fold/bend lines, for receiving at least part of a microfluidic-based diagnostic test, and wherein the detection arrangement is configured to detect/read a diagnostic result from the microfluidic-based diagnostic test, when inserted into the recess/cavity. The medical testing device may include a wireless communication arrangement/unit which is operatively connected to the detector arrangement via the circuit, in order to communicate a detected/read diagnostic result of the detector arrangement via wireless communication. 
IP Reference 1717113.3 
Protection Patent application published
Year Protection Granted 2018
Licensed No
Impact These developments enabled the successful completion of a PhD, and several journal article publications. South African patent filing application number: 2018/06947 UK patent filing application number: 1717113.3
 
Title Configurable low-cost colorimetric reader optimization set-up 
Description The technical prototype developed consists of a configurable set-up for optimization of colorimetric readout from lateral flow test (LFT) strip devices. The set-up consists of an x-y-z stage housed in a low-cost 3D printed enclosure with low-cost optical detection components. Limited research is available regarding optimization of lateral flow readout systems and the test set-up developed aims to provide further insights using low-cost, readily available components for colorimetric reader optimization. Printed circuit boards (PCBs) were designed and manufactured to enable different low-cost configurations consisting of surface mount device (SMD) light emitting diodes (LEDs) and photodiodes to be explored. A 523 nm green LED was used to maximize the absorbance of real world LFTs that utilize nanogold particles, along with a photodiode with a spectral sensitivity between 400 and 900 nm, adapted to human eye sensitivity. The 30 mm × 30 mm PCBs allow for adaptation to hybrid printed modules in future versions of the device. A 3D-printed housing with an x-y-z stage for positioning of the PCB detector modules in relation to the LFTs while preventing external light from interfering was developed. Different inserts were made to allow for both bare LFTs and LFTs housed in plastic cartridges to be tested. Processing was implemented using an Arduino UNO with serial interfacing to a PC for data collection and analysis, and for ease of investigating different front-end amplification stages for the detector modules. A Python-based graphical user interface (GUI) was developed for automated and configurable testing. A model LFT design was used for initial testing based on the Milenia HybriDetect Universal Lateral Flow Assay Kit (Milenia Biotech GmbH, Germany). Model LFTs with a range of RGB values in the pink-purple color spectrum were explored to model the expected results obtained using real world LFTs. Real world Milenia HybriDetect Universal Lateral Flow strips were also tested to validate and optimize the system further. 
Type Of Technology Detection Devices 
Year Produced 2021 
Impact The configurable test set-up enabled fast-tracking of the development of a low-cost colorimetric reader prototype as part of this project. It will assist in the streamlined and optimized development for future versions of low-cost colorimetric reader prototypes for automated readout of LFTs. This work was submitted to the IEEE NANO 2021 international conference as part of an invited talk and a peer-reviewed conference paper. This will assist researchers in streamlining developments for optical readout devices for LFTs. 
URL https://figshare.com/s/24ad0a2c7e1540c4e83d
 
Title Low-cost, portable luminescence detection system with automated sample dispensing 
Description A portable, low cost system to measure luminol concentration in either cuvettes or on glass slides was developed towards an effective point-of-need solution for luminescence detection. Luminol was used to elicit a chemiluminescent reaction at a wavelength of 470 nm within the blue color spectrum. The developed system includes automated dispensing of two reagents in a timed sequence into a cuvette or onto a glass slide to elicit the luminescence reaction. Two syringes, each with a 5 ml volume, are pre-filled with 1) a luminol-based solution and 2) a hydrogen peroxide and distilled water solution. The syringes are connected to a 3D printed housing containing the sample and the optical sensing module and the complete system was housed in a portable box. Volumes can be set by the user to range between 40 and 400 µL. Immediately after both reagents are dispensed and mixed, measurements from the sensitive photodiode optical sensor are recorded for a duration of 30 seconds. The measurements are amplified using a trans-impedance amplifier which converts the low currents measured into usable voltages values, followed by filtering to remove unnecessary noise. Averaging of the measurements over time were used to calculate the luminol concentration, ranging from 10 mg/L to 1 g/L. Further system characterization is currently underway to assess the limit of detection achievable. 
Type Of Technology Detection Devices 
Year Produced 2020 
Impact The low-cost luminescence detection system along with the automated sample dispensing and mixing components, will assist in the development of future versions of low-cost luminescence reader prototypes for automated readout of point-of-care diagnostics utilizing luminescence reactions. This work was submitted to the IEEE NANO 2021 international conference as part of an invited talk and a peer-reviewed conference paper. This will assist researchers in streamlining developments for luminescence detection systems for PoC using portable, low-cost and automated sample preparation mechanisms. 
 
Title Wireless colorimetric reader for resource-limited point-of-care 
Description A hybrid printed electronic prototype of an automated, low-cost colorimetric device employing standard packaging methods was realized. The device consists of cardboard packaging to house printed functionality components. This provides a maintenance-free device that could be used several times, and then disposed of. The device provides automated result readouts from diagnostic tests, and communicates the results wirelessly to a central database using printed radio frequency identification (RFID) tags. For this prototype, a photodiode is connected directly as a colour detector solution with built-in amplification is already provided by the sensor frond end of the RFID integrated circuit (IC) packaged chip. The device is low-cost, with the long-term goal of being environmentally friendly and able to be mass produced, using existing and modified industry processes for printing and packaging. Initial scale up of such devices has been explored, with pick and place techniques being a viable option for future work. 
Type Of Technology Detection Devices 
Year Produced 2018 
Open Source License? Yes  
Impact These developments formed part of the Dr.-Ing degree of Dr Suzanne Smith, and resulted in several journal and conference paper publications. A patent was filed based on this work, demonstrating the potential future impact of these novel developments. Initial user testing of the devices shows promise for use as a tool in future developments towards effective point-of-care diagnostic solutions. 
URL https://publikationen.bibliothek.kit.edu/1000105561
 
Company Name BENEFICIAL BIO LTD 
Description Beneficial Bio is a network of social enterprises run by biologists with the goal of helping labs around the world secure reagents quickly and economically. Beneficial Bio Ltd UK is a non-profit company which supports the development of manufacturing and sales nodes in the global South to produce open source reagents using materials including those emerging from OpenPlant, specifically the Open Enzyme Collection and Biomaker Challenge hardware. The initial pilot partner is in Cameroon with further partnerships being explored in Chile, Ghana, Ethiopia and Nigeria. 
Year Established 2019 
Impact Partnered with MboaLab Biotech in Cameroon to establish the country's first private sector biomanufacturing facility using synthetic biology techniques and open source tools. Employing four full time staff including two scientists. Six interns hosted from local universities, one of which has gone on to full time employment with the company and two have gone on to MSc or PhD programmes in Europe. Projected revenues of $250k+ in 2021 and further funding secured from Volkswagen Stiftung and Open Society Foundations.
Website https://beneficial.bio
 
Company Name Colorifix Ltd. 
Description Colorifix has developed a new method to dye textiles where microbes are used to produce, deposit and fix pigments to fabric. The patent pending process can use engineered microbes NB: Although the company was registered in 2016, we did not gain significant funding until 2018. It is at this point where the LCVD award (and Open Plant) award had positive impact on my profile for investors. 
Year Established 2016 
Impact The patent pending process can use engineered microbes The method developed by Colorifix is sustainable and can be made into a circular economy. Importantly, the production of pigments are from engineered microbes that are produced using synthetic biology methods developed in the UK, supported by RCUK (BBSRC, EPSRC). These include DNA assembly methods, LOOP and BASIC. Importantly the company also has engaged with DNA foundries in London and in Norwich (Earlham Institute). From an environmental standpoint, compared to conventional methods based on petrochemical dyes and dyeing: No hazardous chemicals (no taxes or fines for use/disposal) No extraction of pigment (80% cost of fermented products) 90% reduction of water use 30% reduction in energy use <1% dye waste (3x better than industry standard) Combines two processes: lower carbon footprint
 
Description 1st TReND in Africa (Teaching and Research in Natural Sciences for Development in Africa) Advanced Open Labware workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact The aim of the First Advanced Open Labware Workshop was to assist researchers to develop capabilities and local expertise to accelerate research and development in Africa. The workshop was a collaboration between TReND (Teaching and Research in Natural Sciences for Development in Africa) and the Universities of Cape Town (South Africa), Tuebingen (Germany), Sussex (United Kingdom) and Oxford (United Kingdom), as well as the Council for Scientific and Industrial Research (CSIR, South Africa) and funded by the Volkswagen Foundation.
The workshop was held in Muizenberg, Cape Town, South Africa in April 2018, with a number of facilitators and 24 participants developing the open labware projects: 8 teams with 3 participants per team from Nigeria, Ghana, Malawi, Cameroon, South Africa and Germany. Teams were required to submit proposals for their projects, and successful candidates were asked to formulate and submit a bill of materials required for the project. The various
components were procured prior to the workshop and distributed on the first day to the teams to streamline the progress of the projects.
The course took place over 2 weeks (6 days per week) from the 16th of April until the 28th of April. The daily schedule was structured with a morning presentation or lecture session at 09h00 and then building sessions for the remainder of the morning. Building continued in the afternoons after lunch, and the days were typically wrapped up with an hour long dedicated documentation session for groups to be able to capture the progress made and challenges faced, ultimately to feed back into the open labware space for others to utilize and build on to their work.
The participants reported advances made in their labs as a result of the workshop, with items procured as part of the workshop that they could utilize in their laboratories and institutions in their home countries.
Year(s) Of Engagement Activity 2018
URL https://trendinafrica.org/
 
Description Bahir Dar Biomaker 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 Biomaker Africa workshops were set up to get non-programmers up and running within a day or two. This is due to use of the no-code programming environment XOD, which can be used to introduce biologists to hands-on physical computing. This proves to be a great way of promoting co-creation in interdisciplinary teams - where both the engineers and the biologists can communicate properly! (https://www.hackster.io/jim-haseloff/biomaker-starter-kit-xod-023e8b). In addition, we've doubled down on the use of the 4D Systems touchscreens with XOD and the Biomaker Starter kits, to allow code-free communication between Arduino devices and the touchscreens, with their ViSi-Genie interfaces. We've built better tutorial materials to kick-start this (e.g. https://www.hackster.io/jim-haseloff/biomaker-tutorial-4-programming-the-4ds-touchscreen-3b2006). Details of the 2-day workshops and associated open resources can be found at https://www.biomaker.org
Year(s) Of Engagement Activity 2019
URL https://www.biomaker.org/visiting-workshops
 
Description Biomaker Challenge 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact The Biomaker Challenge calls on interdisciplinary teams to (i) build low-cost sensors and instruments for biology or (ii) develop some biological resource or outreach project. Over a number of years, the initiative has funded over 175 projects and involved hundreds of participants from a wide range of backgrounds. It has proved a great opportunity to learn new skills, collaborate with an interdisciplinary community and, in a short amount of time, develop tools and resources that are useful for real-world applications. Tools and resources developed during the Biomaker Challenge are openly documented and made freely available.
Year(s) Of Engagement Activity 2017,2018,2019,2020
URL https://www.biomaker.org/projectindex
 
Description CDT-Sumitomo online workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact UK-Japan online workshop to discuss advanced research topics and possible translation to applications
Year(s) Of Engagement Activity 2021
 
Description Cafe Synthetique 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Café Synthetique is the monthly meetup for the Cambridge synthetic biology community with informal talks, discussion and pub snacks.
We meet monthly at the Panton Arms to share the latest developments in synthetic biology and related approaches and techniques. Speakers range from students and group leaders to industry professionals and entrepreneurs.
Year(s) Of Engagement Activity 2016,2017,2018,2019,2020
URL https://www.synbio.cam.ac.uk/events/cafe-synthetique/events/cafe-synthetique/past-cafe-synthetique
 
Description Cambridge SynBio Forums 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact The SynBio Forums are sponsored by the University of Cambridge Synthetic Biology Interdisciplinary Research Centre, and feature prominent international speakers and excellent networking opportunities - they provide excellent opportunities to learn more about cutting edge synthetic biology.
Year(s) Of Engagement Activity 2015,2016,2017,2018,2019,2020
URL https://www.synbio.cam.ac.uk/events/forum
 
Description Cell-free Synthetic Biology workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Recent technical advances in the preparation of microbial cell-free extracts have given rise to a new class of highly efficient systems for gene expression that are cheap to deploy and have huge potential benefit for the provision of a wide variety of diagnostics, sensors, vaccines and research materials. Cell-free synthetic biology is thus a topic of growing interest to many groups in Cambridge and the Synthetic Biology IRC is pleased to share its programme of activities to promote and support interdisciplinary work in this space.
Year(s) Of Engagement Activity 2017,2018,2019,2020
URL https://www.synbio.cam.ac.uk/initiatives/cell-free-synthetic-biology
 
Description Creation and running of online training workshops for Biomaker 
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 In response to the COVID lockdown Stephanie Norwood and I, as organisers of the Biomaker initiative, introduced more easily accessible hardware resources and created novel training materials for online teaching of no-code programming techniques for biologists lacking in formal programming skills. (https://www.biomaker.org/nocode-programming-for-biology-handbook). We have distributed around 200 hardware kits and run a series of online workshops via Zoom.
Year(s) Of Engagement Activity 2020,2021
URL https://www.biomaker.org
 
Description Guest speaker for CRISPR genome engineering workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A small workshop was organised to teach participants about the use of CRISPR for genome engineering. I helped plan the workshop, provided technical advice and gave a guest presentation on the use of CRISPR systems for diagnostics.
Year(s) Of Engagement Activity 2020
URL https://www.meetup.com/Cambridge-Synthetic-Biology-Meetup/events/268612875/
 
Description International workshop on viral diagnostics development - South Africa 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We ran a free, 3-day workshop dedicated to practical and theoretical training in the use of cell-free synthetic biology technologies, paper-based microfluidic techniques and open-source electronics and detection systems for low-cost viral diagnostics (LCVD) applications. The workshop consisted of several modules focusing on: Diagnostic needs in South Africa, Application of the diagnostics life cycle, ASSURED criteria for diagnostic tests, Scaling up, Regulation and intellectual property, Practical training in cell-free synthetic biology and low-cost electronics. The workshop involved early- and mid-career academics, government and industry representatives and entrepreneurs in the diagnostics field.
Year(s) Of Engagement Activity 2019
URL https://www.lcvd.org/
 
Description Invited presentation at CRI, Paris 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited presentation: Open Tools for Engineering Biology
Year(s) Of Engagement Activity 2021
 
Description Invited talk at IEEE NANO 2020 Conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited speaker presentation entitled: Printed functionality for point-of-need diagnostics in resource-limited settings was delivered at the virtual IEEE NANO 2020 Conference with questions and discussions afterwards, particularly with focus on Humanitarian and Peace Engineering aspects.
Year(s) Of Engagement Activity 2020
URL https://2020.ieeenano.org/program/invited-speakers/
 
Description Kumasi Biomaker 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 Cambridge Biomaker organisers headed to Ghana to run a two-day workshop at Kumasi Hive, an entrepreneurship and innovation hub and one of the implementing arms of the Biomaker initiative. Twenty participants gathered in Kumasi for an accelerated course in programming hardware for low-cost, open-source bioinstrumentation. Half of the participants had worked with the Biomaker system before, and together with the new participants, further developed their projects by learning to program a customisable touchscreen interface for their existing hardware. The fast-paced, energetic training sessions were broken up by project presentations from the teams, talks from researchers from Cambridge and the nearby Kwame Nkrumah University of Science and Technology.
Year(s) Of Engagement Activity 2019
URL https://www.biomaker.org/news/2019/8/29/biomaker-in-ghana-conversations-from-a-2-day-workshop-with-i...
 
Description No-code programming online 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 Organised and delivered an online workshop to provide training for non-programmers in the use of microcontrollers for scientific applications. Distributed standard hardware for the training sessions ahead of the workshop. Dec 8th and 9th 2021.
Year(s) Of Engagement Activity 2021
URL https://www.biomaker.org
 
Description No-code programming workshop, University of Veracruz, Mexico 
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 Online workshop, co-sponsored with Prof. Mario Arteaga, University of Veracruz, Mexico - introducing research students to no-code programming for scientific instrumentation.
Year(s) Of Engagement Activity 2022
URL https://www.biomaker.org
 
Description Open Technology Week 
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 Open Technology Week showcases and celebrates open source technologies in research and education developed across Cambridge and beyond. This multi-day event includes lectures, demos and workshops that explore examples of open technologies and their implications, featuring projects by Biomaker Challenge teams as well as makers in the community.
Year(s) Of Engagement Activity 2015,2016,2017,2018,2019
URL https://www.synbio.cam.ac.uk/initiatives/Open_Technology_Week/
 
Description Presentation on open source and technology transfer at UK government meeting with World Health Organisation COVID Technology Access Pool 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Presentation on open source models and importance of technology transfer for diagnostics related biotechnology to UK government BEIS and FCO representatives, industry associations, companies. This was on behalf of UN Technology Access Partnership and drew on models of technology transfer being explored by OpenPlant. The event overall led to a longer discussion between C-TAP and the UK government.
Year(s) Of Engagement Activity 2020
 
Description Pretoria Biomaker 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 Biomaker Africa workshops were set up to get non-programmers up and running within a day or two. This is due to use of the no-code programming environment XOD, which can be used to introduce biologists to hands-on physical computing. This proves to be a great way of promoting co-creation in interdisciplinary teams - where both the engineers and the biologists can communicate properly! (https://www.hackster.io/jim-haseloff/biomaker-starter-kit-xod-023e8b). In addition, we've doubled down on the use of the 4D Systems touchscreens with XOD and the Biomaker Starter kits, to allow code-free communication between Arduino devices and the touchscreens, with their ViSi-Genie interfaces. We've built better tutorial materials to kick-start this (e.g. https://www.hackster.io/jim-haseloff/biomaker-tutorial-4-programming-the-4ds-touchscreen-3b2006). Details of the 2-day workshops and associated open resources can be found at https://www.biomaker.org.
Year(s) Of Engagement Activity 2019
URL https://www.biomaker.org/visiting-workshops
 
Description Production and distribution of Biomaker training materials for online training. 
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 Provision of free online training materials to complement a starter pack is based on the Grove All-in-One Beginner Kit for Arduino. We have developed a visual guide, which provides step-by-step instructions of how to control the board using the XOD visual programming environment. The first lessons are available for download now. XOD tutorial code is also available to accompany this guide. In addition, training videos can be viewed online.
Year(s) Of Engagement Activity 2020,2021
URL https://www.biomaker.org/nocode-programming-for-biology-handbook
 
Description Seminars at University of Cape Town 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Drs Jenny Molloy and Lalitha Sundaram were invited to give a seminar at the University of Cape Town's Research Contracts & Innovation division. Approximately 35 people attended the event; the audience was composed of researchers involved in intellectual property, innovation, and biotechnology.
Dr Molloy's talk was entitled "Open Intellectual Property as a Strategy for Innovation in the Bioeconomy" and Dr Sundaram's "Innovations in biotech: getting the regulation right". Both talks sparked discussions among the audience, on the state of regulatory frameworks in South Africa and on current practices surrounding intellectual property.

A number of contacts were made, notably with industrial actors in the plant biotech space as well as with biosafety analysts in South Africa.
Year(s) Of Engagement Activity 2019
 
Description Sequencing workshop in Ghana 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact We ran a sequencing workshop for scientists studying pathogens. This workshop provided hands on training in nanopore sequencing to ~20 scientists from over the African continent.
Year(s) Of Engagement Activity 2018
 
Description Smart Imaging Sandpit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Workshop to introduce the use of AI techniques, image processing and low-cost hardware for real world applications in low resource settings - co-organised by the Synthetic Biology IRC, Sensors SRN and Global Challenges SRI at the University of Cambridge, with support from BITRI Botswana, Royal College of Arts and Mathworks. The workshop led to 5 projects being conceived and funded, and competetive pitches.
Year(s) Of Engagement Activity 2019
URL https://www.gci.cam.ac.uk/events/cgc-co-creation-events/smart-imaging-development-sandpit-and-seed-f...
 
Description Talk and participation at SAIEE national 2019 workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Talk given entitled Functional Printing for a Future Africa, to align with the theme of the workshop: Engineering an Africa for the Future.
Parallel sessions were carried out in an interactive manner, with discussions and interactions in the various sessions, with approximately 50 participants per session.
Year(s) Of Engagement Activity 2019
URL https://www.saiee.org.za/calendar/EventDetails.aspx?eeid=29201
 
Description Xalapa Biomaker 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 This Biomaker workshop was run at the University of Veracruz, Xalapa, Mexico, and designed to get non-programmers up and running within a day or two. This was due to use of the no-code programming environment XOD, which can be used to introduce biologists to hands-on physical computing. This proves to be a great way of promoting co-creation in interdisciplinary teams - where both the engineers and the biologists can communicate properly! (https://www.hackster.io/jim-haseloff/biomaker-starter-kit-xod-023e8b). In addition, we've doubled down on the use of the 4D Systems touchscreens with XOD and the Biomaker Starter kits, to allow code-free communication between Arduino devices and the touchscreens, with their ViSi-Genie interfaces. We've built better tutorial materials to kick-start this (e.g. https://www.hackster.io/jim-haseloff/biomaker-tutorial-4-programming-the-4ds-touchscreen-3b2006). Details of the 2-day workshops and associated open resources can be found at https://www.biomaker.org
Year(s) Of Engagement Activity 2019
URL https://www.biomaker.org/visiting-workshops