US Partnering Award: "Nanoporous microsystems: A new view of epithelial physiology, on a chip"
Lead Research Organisation:
University of Nottingham
Department Name: Faculty of Engineering
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Organisations
- University of Nottingham (Lead Research Organisation, Project Partner)
- Rochester Institute of Technology (Collaboration, Project Partner)
- University of Rochester (Collaboration, Project Partner)
- Kode Biotech Ltd (Collaboration)
- UNIVERSITY OF NOTTINGHAM (Collaboration)
- Ibidi (Collaboration)
- University of Auckland (Collaboration)
- SiMPore Inc (Collaboration)
- University of Würzburg (Collaboration)
Publications
Abayzeed SA
(2017)
Sensitive detection of voltage transients using differential intensity surface plasmon resonance system.
in Optics express
Henry S
(2018)
Rapid one-step biotinylation of biological and non-biological surfaces.
in Scientific reports
Madeijski, G
(2017)
Magnesium Fluoride Nanomembranes for the study of biological cells by Raman Microspectroscopy
in ACS Nano
Madejski G
(2018)
TEM Tomography of Pores with Application to Computational Nanoscale Flows in Nanoporous Silicon Nitride (NPN).
in Membranes
McCloskey MC
(2022)
The Modular µSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro.
in Advanced healthcare materials
Petrova RS
(2018)
Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells.
in American journal of physiology. Cell physiology
Pérez-Cota F
(2015)
Thin-film optoacoustic transducers for subcellular Brillouin oscillation imaging of individual biological cells.
in Applied optics
Pérez-Cota F
(2020)
Picosecond ultrasonics for elasticity-based imaging and characterization of biological cells
in Journal of Applied Physics
Pérez-Cota F
(2016)
High resolution 3D imaging of living cells with sub-optical wavelength phonons.
in Scientific reports
Smith RJ
(2015)
Optically excited nanoscale ultrasonic transducers.
in The Journal of the Acoustical Society of America
| Description | We have nucleated through this award an international collaboration spanning academic (Universities of Rochester, Nottingham) and industrial (SimPore Inc, ibidi GmBH, Kode Biotech Ltd) partners in the creation and exploitation of novel technologies in the field of epithelial microdevices. In the future these novel devices may subsitute for animal work, provide platforms for novel biosensing and bioimaging assys, personalised medicine, and novel miniaturised devices for the study and manipulation of living systems using non-invasive photonic means. This consortium had its inaugural meeting in August 2016 in Rochester, NY and has so far shared team members internationally on 3 separate research visits and placements between Rochester and Nottingham. In addition, several serendipitous discoveries have been opened up to exploitation within the consortium, including novel surface chemistries, nanomaterials, and photoniclally-manipulable cell lines capable of modulating physiology non-invasively by optical means.We have developed a novel nanomaterial (very thin magnesium fluoride) which is an ideal, nanoporous substrate on which to grow epithelial cells. We have also confirmed both that cells can grow on these nanomaterials as well as their suitability for the latest high-resolution imaging methods using a Raman microspectrometry system also developed in our laboratory. Using these tools we are able to image the movement of water through and across the cells, with the goal of measuring epithelial transport as a platform for drug discovery, physiological research, and personalised medicine. We have further demonstrated that these methods are applicable to the real-time visualisation of fluid transport in living plant tissue, and obtained funding from the Leverhulme Trust to pursue the work in this important area of water resiliance and the assessment of plant physiology and water stress in real time. We have further discovered a novel biosensing technology based on these nanoporous membrane devices (SERS biosensors), with major potential to revolutionise current approaches to diagnostics and point-of-care monitoring of biomarkers and bioanalytes. This technology has been jointly patented between the Universities of Nottingham and Rochester and is being developed for commercial exploitation by industrial partners in the USA (SiMPore Inc, Rochester, NY) and Europe (ibidi GmbH, Munich, Germany). With industrial collaborators in New Zealand (Kode Biotech Ltd) we have further developed novel surface chemistries and molecules for the polarisation and differentiation of mature epithelial tissue models on arbitrary materials - both porous and non-porous. This work is being IP protected and will be commercialised by Kode Biotech Ltd via newly-created Kode Diagnostics Ltd, under a joint licensing agreement which is being negotiated between the parties. A serendipitously discovered family of small molecules has further been shown through our work as being capable of modulating tight junctions in a non-invasive and reversible fashion, which is currently being assessed as a drug delivery enhancement agent for immunotherapies and chemotherapies, aiding their delivery across tissue barriers to their targets within the body. This represents early-stage development which has already attracted the interest of NHS clinicians as an adjunctive prospective therapeutic delivery enhancer of macromolecular therapies across tissue barriers in a reversible fashion. New collaborations nucleated with Exeter (microbiology and microfluidics), Nottingham Respiratory Medicine (human lung barrier function and drug delivery), and Oncology at Nottingham (drug delivery and oncophysiology) |
| Exploitation Route | Our consortium is working to create the physical underpinnings for novel epithelial microdevices - embodying robust epithelial tissue barriers in vitro with the aim of replacing animal work with robust, reproducible assays for tissue physiology, barrier function, drug delivery, and toxicity. Physiological parameters can be adjusted and manipulated noninvasively using light, while reading out via electrical, electrochemical, biosensing (SERS) and non-invasive Raman microspectroscopy. In addition to mammalian and human physiology and pharmacology our non-invasive imaging methods have found application in the real-time study of water uptake and transport by living plants.Our novel devices and methods to grow and investigate cultures of epithelial cells may become a new standard for physiological studies, providing non-invasive readout of key transport processes against which novel drug targets, compounds, therapies, or personalised approaches may be tested. Our novel biosensor technology is a revolutionary platform allowing unprecedented sensitivity and functionality in the sensitive and reproducible quantitation of bioanalytes in healthcare as well as industrial contexts. Our drug delivery enhancement agents offer the potential to deliver next-generation macromolecular therapies across tissue barriers non-invasively, using a fraction (1/1000) of the currently required dose. Our non-invasive label free method of directly imaging water transport within and across living biological tissues is finding uptake across the field, including the physiological assessment of water transport and uptake in living plants. |
| Sectors | Agriculture, Food and Drink,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | We have organised the first of our annual workshops on nanoporous microdevices for physiology - this took place at the University of Rochester in August 2016. Audience included 15 academics from across the USA, local Rochester graduate and undergraduate students, invited participants from the wider photonics community at Rochester, and was be open to registration to any eligable student throughout the USA/Canada. Nottingham participants included members of the Webb lab as well as TTO representatives and collaborators on epithelial transport and physiology, and industrial collaborators from SimPore Inc, Rochester NY and Kode Biotech Ltd, Auckland, New Zealand. In addition to our inaugural workshop and symposium, which we are planning to repeat in Nottingham UK during summer 2017, we have instituted the third in our researcher exchance program between Rochester and Nottingham with a 9-month hosted visit of Mr Greg Madejski to Nottingham through August 2016. Mr Madejski has developed himself into a potent weilder of nanofabrication techniques to develop novel nanomaterials for cell culture and biosensing, resulting in the creation of a series of nanoporous and microporous substrates for cell culture and biosensors.Our research has provided a new platform for the study of epithelial transport processes, which may lead to a step change in personalised medicine by providing epithelia on a chipas well as new devices for market which are currently under technology transfer with a USA spinout company from the University of Rochester (Simpore Inc). In addition to these novel sample preparations and cell culture substrates, we have translated the nanoporous membrane technologies co-developed with Rochester into a new class of SERS biosensor which is presently in a rapid development phase for commercialisation between a consortium of academic (Nottingham, Rochester) and industrial (SimPore Inc, Ibidi GmBH) partners. We have transformed this family of novel nanomaterials into a platform technology capable of SERS biosensing, cell culture, and real-time assessment of small and macromolecular transport across and within living systems. In addition we have jointly created (with Kode Biotech Ltd) a pair of novel surface chemistries to encourage the proper polarisation of epithelial barrier tissue models on arbitrary substrates and material porosities. In addition we have used this platform of novel bioreactors to develop and test a novel family of drug delivery enhancement agents capable of booosting drug delivery across these layers in vitro. We have also developed in paralell a set of epithelial tissues from the gut, eye and lung which are capable of optical modulation of their fundamental physiology, with the goal of controlling and manipulating physiology in these important model systems non-invasively using photonic means. In the future, these new epithelial microdevices will offer a platform technology for the assessment of physiology, drug delivery and toxicity in vitro, and replace animal experiments by providing an alternative human-relevant means of assessing impact on physiology and health in vitro. A new, multi-lateral collaboration between academic (Nottingham, Rochester, RIT) and industrial (Kode Biotech, ibidi, SiMPore) partners, whose scope and scale will be further cemented and broadened by the upcoming Munch symposium in September 2018 and one additional international symposium at Nottingham in summer 2019 - approval for this further activity has been received from BBSRC, via a requested no-cost extension to the award. |
| First Year Of Impact | 2016 |
| Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | HERMES Travel Fellowship |
| Amount | £3,000 (GBP) |
| Organisation | University of Nottingham |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2013 |
| End | 06/2014 |
| Description | Hermes Innovation Fellowship |
| Amount | £27,500 (GBP) |
| Funding ID | Commercialisation of a nanoporous, re-writable, SERS biosensor |
| Organisation | University of Nottingham |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2016 |
| End | 07/2016 |
| Description | NSF PFI:ATT |
| Amount | $199,000 (USD) |
| Organisation | National Science Foundation (NSF) |
| Sector | Public |
| Country | United States |
| Start | 06/2016 |
| End | 06/2018 |
| Description | Proximity to Discovery |
| Amount | £16,500 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2016 |
| End | 02/2017 |
| Description | University of Nottingham Regenerative Medicine and Stem Cells Research Priority Area |
| Amount | £15,000 (GBP) |
| Funding ID | A2QRVX |
| Organisation | University of Nottingham |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 09/2017 |
| End | 07/2018 |
| Description | Whittaker Foundation International Scholars Program |
| Amount | $34,500 (USD) |
| Organisation | Whitaker Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 08/2015 |
| End | 07/2016 |
| Title | Novel surface chemistries for polarising epithelial tissues on arbitrary substrates |
| Description | In collaboration with Kode Biotech Ltd we have co-developed a set of novel molecules for the surface chemistry modification of arbitrary substrate, such that epithelial tissues can be adhered and polarised on any material - porous or non-porous - in contrast to decades of previous work. These molecules are presently under IP negotiation for protection in multiple jurisdictions globally. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | Epithelial tissues are classically viewed as incapable of proper differentiation, polarisation, or maturation towards normal physiological function on non-porous substrates. Requiring porous substrates has limited the use of epithelial tissues in epithelial microdevices especially in an imaging context. Opening the door for proper polarisation on arbitrary porous and non-porous substrates has major potential in the design of tissue-on-chip and lab-on-chip devices for the biosensing and bioimaging readout of biomarkers, physiology, fluid and molecular transport, and barrier function. This ability will be of wide interest to industry and academia, and is currently under IP review with a view to protecting the IP in several jurisdictions. |
| Title | PreFACE - Predictive Focus Automatic Correction Engine |
| Description | PreFACE is a novel image processing method capable of extracting, in real time, from a single image, accurate defocus correction signals for the instantaneous closed-loop control of focus in high-content imaging. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | Development of commercial product (Cairn Research Ltd), development of high-content screening platform (Ibidi GmbH), Development of open-source PreFACE engine for the open-source microscopy community (µManager). |
| Title | PreFACE - Predictive Focus Automatic Correction Engine |
| Description | This novel technology, arising from an industrially-focussed MEng project in conjunction with ibidi GmbH, addresses one of the major outstanding problems in biomedical science - that of maintaining the focus of a microscopy system over long time periods in the face of thermal and mechanical disturbance. This is especially important in the context of big pharma assays for behaviour and morphology, in addition to research and academic studies. The method is unique, patentable, and is capable of precisely determining both the magnitude and direction of defocus of an imaging system from a single image or series of images. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | ibidi GmbH has incorporated PreFACE into their new developmental imaging system product. Cairn Research Ltd, Faversham, Kent is in licensing discussions with the University of Nottingham tech transfer office about funding IP capture and developing the system to a full commercial product to install within the microscopy platforms of 3 of the 4 major global manufacturers - Nikon, Olympus, Leica. At this stage the IP is not yet protected, and the technology has been made available to the industrial partners for developmental and commercialisation purposes. |
| Description | Consortium for the real-time control of microscope focus in high-content screening |
| Organisation | Ibidi |
| Country | Germany |
| Sector | Private |
| PI Contribution | Resulting from a MEng industrially-focussed research project, a student-led technology development for the real-time extraction of defocus error signal from microscope images was invented (PreFACE - the Predictive Focus Automatic Correction Engine). This innovation is currently being developed by Cairn Research Ltd (Faversham, Kent) into a commercial product capable of being retrofitted to 3 of the major 4 microscope manufacturers globally (Nikon, Olympus, Leica). Etaluma Inc, who make in-incubator imaging devices, have also implemented this design in joint development with Cairn Research. |
| Collaborator Contribution | Cairn Research Ltd are key commercial implementors - funding IP protection and development under license from the University of Nottingham. |
| Impact | Commercial PreFACE product under industrial development, open-source PreFACE engine in development for the open-source microscopy community. |
| Start Year | 2017 |
| Description | Epithelia-on-a-chip Consortium |
| Organisation | Rochester Institute of Technology |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have developed a bespoke Raman microspectroscope which we are using to study the transport of fluid by layers of epithelial cells. We have provided cell cultures and assays, hosted a US graduate student in our lab, implemented epithelial cultures on novel nanoporous nanomembrane substrates, and begun to encapsulate cell cultures in microfluidic devices for physiological measurements. We have further advised the US group on approaches to live cell imaging and maintenance in vitro which has led to a step-change in operational workflow in the Nanomembranens Research Group (NRG) at Rochester. |
| Collaborator Contribution | The NRG have produced and characterised novel nanoporous nanomembrane materials for our project, including a world-first nanoporous magnesium fluoride nanomembrane which is compatible with Raman microspectroscopy in a regime appropriate for live cell work. the UoR group has contributed access to expertise and fabrication facilities unavailable in this country, and provided a leg up into the world of nanomaterials and bioengineering microdevices which has provided a step change in our own experimental approach. This partnership has been extended to a wider constortium involving Rochester Institute of Technology (RIT) as well as joint spinout company (SimPore Inc). In-kind contributions include bespoke wafer design and manufacture and multiple years of technical support as well as supply of novel nanostructured materials optimised for Raman microspectroscopy on living cells. |
| Impact | Two travel grants have been funded, allowing reciprocal research visits by Dr Webb (UoN) and Prof McGrath (UoR) to each others laboratories. In addition the travel funding provided for a 3 month secondment of Greg Madeijski (UoR) to Nottingham, and a week-long knowledge transfer interaction with Dr Pascut (UoN) embedded within the NRG for a short period. We are preparing major joint funding bids to fund both the interaction and the epithelia-on-chip concept, and Dr Webb is now co-supervising the PhD of Mr Madeijski along with Prof McGrath. TTO outputs are currently at the disclosure stage at both Rochester and Nottingham, under mutual NDA/CDA. In 2015-16 we have hosted Mr Madejski at Nottingham under a Whittaker Foundation international scholars programme award, which has led to the serendipitous discover of a novel biosensor based on nanoporous nanomembrane technology - this is described elsewhere. |
| Start Year | 2013 |
| Description | Epithelia-on-a-chip Consortium |
| Organisation | SimPore Inc |
| Country | United States |
| Sector | Private |
| PI Contribution | We have developed a bespoke Raman microspectroscope which we are using to study the transport of fluid by layers of epithelial cells. We have provided cell cultures and assays, hosted a US graduate student in our lab, implemented epithelial cultures on novel nanoporous nanomembrane substrates, and begun to encapsulate cell cultures in microfluidic devices for physiological measurements. We have further advised the US group on approaches to live cell imaging and maintenance in vitro which has led to a step-change in operational workflow in the Nanomembranens Research Group (NRG) at Rochester. |
| Collaborator Contribution | The NRG have produced and characterised novel nanoporous nanomembrane materials for our project, including a world-first nanoporous magnesium fluoride nanomembrane which is compatible with Raman microspectroscopy in a regime appropriate for live cell work. the UoR group has contributed access to expertise and fabrication facilities unavailable in this country, and provided a leg up into the world of nanomaterials and bioengineering microdevices which has provided a step change in our own experimental approach. This partnership has been extended to a wider constortium involving Rochester Institute of Technology (RIT) as well as joint spinout company (SimPore Inc). In-kind contributions include bespoke wafer design and manufacture and multiple years of technical support as well as supply of novel nanostructured materials optimised for Raman microspectroscopy on living cells. |
| Impact | Two travel grants have been funded, allowing reciprocal research visits by Dr Webb (UoN) and Prof McGrath (UoR) to each others laboratories. In addition the travel funding provided for a 3 month secondment of Greg Madeijski (UoR) to Nottingham, and a week-long knowledge transfer interaction with Dr Pascut (UoN) embedded within the NRG for a short period. We are preparing major joint funding bids to fund both the interaction and the epithelia-on-chip concept, and Dr Webb is now co-supervising the PhD of Mr Madeijski along with Prof McGrath. TTO outputs are currently at the disclosure stage at both Rochester and Nottingham, under mutual NDA/CDA. In 2015-16 we have hosted Mr Madejski at Nottingham under a Whittaker Foundation international scholars programme award, which has led to the serendipitous discover of a novel biosensor based on nanoporous nanomembrane technology - this is described elsewhere. |
| Start Year | 2013 |
| Description | Epithelia-on-a-chip Consortium |
| Organisation | University of Rochester |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have developed a bespoke Raman microspectroscope which we are using to study the transport of fluid by layers of epithelial cells. We have provided cell cultures and assays, hosted a US graduate student in our lab, implemented epithelial cultures on novel nanoporous nanomembrane substrates, and begun to encapsulate cell cultures in microfluidic devices for physiological measurements. We have further advised the US group on approaches to live cell imaging and maintenance in vitro which has led to a step-change in operational workflow in the Nanomembranens Research Group (NRG) at Rochester. |
| Collaborator Contribution | The NRG have produced and characterised novel nanoporous nanomembrane materials for our project, including a world-first nanoporous magnesium fluoride nanomembrane which is compatible with Raman microspectroscopy in a regime appropriate for live cell work. the UoR group has contributed access to expertise and fabrication facilities unavailable in this country, and provided a leg up into the world of nanomaterials and bioengineering microdevices which has provided a step change in our own experimental approach. This partnership has been extended to a wider constortium involving Rochester Institute of Technology (RIT) as well as joint spinout company (SimPore Inc). In-kind contributions include bespoke wafer design and manufacture and multiple years of technical support as well as supply of novel nanostructured materials optimised for Raman microspectroscopy on living cells. |
| Impact | Two travel grants have been funded, allowing reciprocal research visits by Dr Webb (UoN) and Prof McGrath (UoR) to each others laboratories. In addition the travel funding provided for a 3 month secondment of Greg Madeijski (UoR) to Nottingham, and a week-long knowledge transfer interaction with Dr Pascut (UoN) embedded within the NRG for a short period. We are preparing major joint funding bids to fund both the interaction and the epithelia-on-chip concept, and Dr Webb is now co-supervising the PhD of Mr Madeijski along with Prof McGrath. TTO outputs are currently at the disclosure stage at both Rochester and Nottingham, under mutual NDA/CDA. In 2015-16 we have hosted Mr Madejski at Nottingham under a Whittaker Foundation international scholars programme award, which has led to the serendipitous discover of a novel biosensor based on nanoporous nanomembrane technology - this is described elsewhere. |
| Start Year | 2013 |
| Description | Laser ultrasound dynamic imaging for the study of epithelial transport and cell volume regulation |
| Organisation | University of Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have partnered with a collaborating group in Advanced Optics, led by Prof Matt Clark, and jointly developed a laser ultrasound instrument capable of revealing mechanical contrast from living biological cells at below the optical diffraction limit. Through a joint PhD supervision (Fernando Perez-Cota, viva passed in Feb 2016) we have demonstrated and applied this method to an array of biological cell types to reveal morphology and subcellular detail. We have recently extended this approach into dynamic imaging of hydrodynamics by exploiting the availability of innocuous heavy isotopes of water (D2O) in order to reveal fluid fluxes into and across cells by monitoring changes in their accoustic properties in the presence of these denser solutions. |
| Collaborator Contribution | The Clark lab (SIOS) are experts in ultrasonic methods for non-destructive testing of materials. Together we have applied these methods at an unprecedentedly small scale, in order to target living biological cells. This involved the design and construction of a novel nanotransducer to launch ultrasonic waves under picosecond ultrasound interrogation, with the dual purpose of providing optical shielding from the exciting laser wavelengths which are injurious to living tissue. An entire bespoke microscope system has been created and implemented with phase contrast optics in order to perform correlative imaging with the novel method. Future work will focus on using picosecond ultrasound as a complementary method for revealing hydrodynamics to our main Raman microspectroscopy approach, which suffers certain crucial limitations in imaging at the required scales to probe dynamics across and between mammalian cells. This approach may result in a generalised method for contrast improvement or enhancement in cellular ultrasound imaging by manipulating density contrast within biomaterials - both living and fixed. As a dynamic method for assessing transmembrane or transcellular transport of fluid in living systems the method is under development, crossing engineering hurdles to make our imaging system compatible with life processes over extended periods. |
| Impact | The first ultrasonically-created images in living cells have been published in Nature Scientific Reports. The recent discovery that heavy water can reveal mechanical contrast and thus allow hydrodynamics to be directly visualised has yielded a novel method which will be an important correlative approach with which we can independently investigate epithelial hydrodynamics using this technologically-distinct and novel approach. |
| Start Year | 2014 |
| Description | Novel commercial bioreactors for dynamic cellular assays |
| Organisation | Ibidi |
| Country | Germany |
| Sector | Private |
| PI Contribution | We have developed novel microporous cell culture substrates in collaboration with the University of Rochester, NY. These devices are inherently designed to be compatible with the commercial bioreactor microfluidic platform currently marketed by ibidi GmBH, sold under cross-selling agreements with our other industrial collaborator SimPore Inc (Rochester, NY). |
| Collaborator Contribution | We have partnered with ibidi GmBH (Munich) - a leading market player in biomedical imaging consumables market, with a presence in 47 global markets. In collaboration with our other industrial partner, SimPore Inc (Rochester, NY) we are developing prototype consumable devices based on our novel Raman-silent microporous MgF2 membrane materials - developed jointly with the University of Rochester. This foundation has led to fruitful interactions including student placements with the company in Munich. This interaction has led to the in-kind supply of microfluidic constructs and components for the creation of prototype devices for testing in our lab. |
| Impact | Student research visit (August 2016) leading to development of prototype illumination device for development imaging system. Prototype bioreactor consumables for consideration in the Raman-silent cellular imaging market (epithelia on a chip). We have an agreement in principle for the creation of full commercial prototypes for market testing once the IP issues have been agreed between parties (in process). |
| Start Year | 2016 |
| Description | Novel surface chemistries for polarisation of epithelial tissues on arbitrary surfaces |
| Organisation | Kode Biotech Ltd |
| Country | New Zealand |
| Sector | Private |
| PI Contribution | Kode Biotech Ltd has contributed know-how and synthetic and analytical capacity to create a set of novel surface chemistry to our specifications, designed to coat in a single step any given surface and expose appropriate surface chemistries to actively drive the polarisation and maturation of epithelial tissues in vitro. Our Nottingham lab has contributed the cellular biology and functional imaging and analysis tools to assess the maturity and polarisation of these epithelial tissue mimics on a range of materials in vitro. Dr Webb was appointed as a Research Fellow of the Centre for Kode Technologies at the Auckland University of Technology, New Zealand in July 2017. |
| Collaborator Contribution | We have co-developed a set of proprietary surface modification agents based on the Kode FSL platform which, when applied to arbitrary surfaces, bind and expose surface chemistries appropriate for the attachment and proper differentiation, polarisation and maturation of in vitro models of epithelial tissues. Importantly these molecules are capable of this remarkable feat even on non-porous surfaces, in contrast to decades of previous work. The IP and scientific implications of these observations are under rapid development via the Tech Transfer apparatus at Nottingham and the company is aggressively leading their commercialisation. |
| Impact | A pair of manuscripts are under preparation, and an additional manuscript in Scientific Reports was published in Feb 2018. Two potential IP filings are in process. An invited talk has been delivered by Prof Steven Henry to Nottingham in Nov 2016 during a sponsored research visit to the Optics and Photonics Research Group. An invited talk was delivered by Prof Steven Henry to our inaugural Epithelia-on-a-chip consortium meeting in August 2016 at the University of Rochester, NY. |
| Start Year | 2015 |
| Description | Real-time functional volumetry via ratiometric fluorescence imaging in living systems |
| Organisation | University of Auckland |
| Country | New Zealand |
| Sector | Academic/University |
| PI Contribution | The Webb lab collaborates extensively with the Molecular Vision Laboratory, University of Auckland Department of Physiology, in the field of live-cell imaging and dynamic physiology of volume regulation and fluid transport in epithelia of the eye. This includes joint PhD supervision and the Honorary appointment of Dr Webb to the University of Auckland Department of Physiology through 2019. The collaboration continues to yield regular joint publications, research visits, and joint funding applications. |
| Collaborator Contribution | The Molecular Vision Laboratory are world experts in the mapping and functional imaging of epithelial transport systems in living and fixed tissues of the eye (ocular lens, retina). In addition to joint development of imaging technologies and assays for the real-time capture of dynamic events from living cells and tissues, the collaboration has resulted in 2 joint PhD students and a path to regular student and researcher exchanges under the Universitas21 framework (commencing Q4/18) |
| Impact | Petrova R.S., Webb K.F., Vaghefi E., Walker K., Schey K.L., Donaldson P.J. Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells. Am J Physiol Cell Physiol 314: C000-C000, 2018. doi:10.1152/ajpcell.00214.2017. |
| Start Year | 2014 |
| Description | Real-time hydrodynamic imaging in living systems |
| Organisation | University of Wurzburg |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | With colleagues at Würzburg, the Webb lab have developed a pair of related fluorescent nanoparticle biosensors capable of reading out in real time the diffusion of water within living systems at sub-micron resolution. The technologies have been synthesised at Nottingham in interdisciplinary collaboration with the Pharmacy school, and tested and calibrated at Würzburg. |
| Collaborator Contribution | Würzburg is a world centre of excellence in the subcellular dynamics of small-molecule signalling systems. Our novel nanosensors, jointly developed, are the perfect control system to establish the fundamental limits of diffusion of small molecules within living systems, thereby capturing the fundamental biophysics and constraints dictating the kinetics and distribution of water within living system, cells, and subcellular structures. |
| Impact | A pair of distinct nanoparticle biosensors (130nm polymer particles, 10nm semiconductor particles) have been developed and are currently under consideration for patent at the University of Nottingham |
| Start Year | 2016 |
| Description | Respiratory tissues on chip collaboration |
| Organisation | University of Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Respiratory medicine - new collaboration to establish and evaluate human primary lung epithelial/smooth muscle co-cultures as models of barrier function for drug delivery, and separately for the evaluation of toxic effects of engine-generated nanoparticles |
| Collaborator Contribution | Contribute human primary lung cells and expertise in co-culture to perform analysis of drug delivery, barrier function, and DNA methylation. |
| Impact | Joint award of MRC Confidence in Concept award to examine drug delivery in the human lung. Respiratory Medicine (Rachel Clifford) collaborates with Optics & Photonics (Kevin Webb) - multidisciplinary medicine/engineering |
| Start Year | 2019 |
| Description | SERS biosensing |
| Organisation | SimPore Inc |
| Country | United States |
| Sector | Private |
| PI Contribution | We have serendipitously discovered that a novel Surface Enhanced Raman Scattering (SERS) biosensor can be fabricated at scale using semiconductor processing methods. This novel technology has been patented by a team of inventors spanning Nottingham (Webb, Pascut) and Rochester (Madejski, McGrath), with a prior date of 1st October 2015. This method of sensor fabrication is a game-changer for the scalable manufacture of porous biosensors with novel functionalities, and will enable the design and optimisation of devices for diagnostics and point-of-care therapeutic information-gathering based on the highly sensitive detection of particular bioanalytes. The Nottingham contribution has been to complete the final manufacturing steps, and to assess the biosensor performance using our state-of-the-art bespoke Raman microspectrometer. The Nottingham TTO liased with Rochester to lead the patent, which was filed in the USA for strategic reasons. |
| Collaborator Contribution | The team at Rochester provided expert manufacturing design and silicon fabrication which provided the underpinning technology for the novel biosensor. Drawing on established background IP held by SimPore (as a spin-out company from Rochester) to add significant value to existing technology as well as enabling the creation of an entirely new class of scalably-manufactured biosensors. Mr Madejski, as co-inventor, has translated his tenure at Nottingham into a significant, serendipitous benefit with major potential to revolutionise disease diagnosis and biomarker detection in a range of contexts. |
| Impact | This collaboration is multidisciplinary, spanning semiconductor manufacture, bioengineering, optical engineering, and biochemistry/electrochemistry. The outputs so far include a patent-protected IP platform, as well as the creation of commercial-quality prototypes of a novel biosensor platform which are presently undergoing market feedback in collaboration with commercial partners (and logical licensees) SimPore Inc. |
| Start Year | 2015 |
| Description | SERS biosensing |
| Organisation | University of Rochester |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have serendipitously discovered that a novel Surface Enhanced Raman Scattering (SERS) biosensor can be fabricated at scale using semiconductor processing methods. This novel technology has been patented by a team of inventors spanning Nottingham (Webb, Pascut) and Rochester (Madejski, McGrath), with a prior date of 1st October 2015. This method of sensor fabrication is a game-changer for the scalable manufacture of porous biosensors with novel functionalities, and will enable the design and optimisation of devices for diagnostics and point-of-care therapeutic information-gathering based on the highly sensitive detection of particular bioanalytes. The Nottingham contribution has been to complete the final manufacturing steps, and to assess the biosensor performance using our state-of-the-art bespoke Raman microspectrometer. The Nottingham TTO liased with Rochester to lead the patent, which was filed in the USA for strategic reasons. |
| Collaborator Contribution | The team at Rochester provided expert manufacturing design and silicon fabrication which provided the underpinning technology for the novel biosensor. Drawing on established background IP held by SimPore (as a spin-out company from Rochester) to add significant value to existing technology as well as enabling the creation of an entirely new class of scalably-manufactured biosensors. Mr Madejski, as co-inventor, has translated his tenure at Nottingham into a significant, serendipitous benefit with major potential to revolutionise disease diagnosis and biomarker detection in a range of contexts. |
| Impact | This collaboration is multidisciplinary, spanning semiconductor manufacture, bioengineering, optical engineering, and biochemistry/electrochemistry. The outputs so far include a patent-protected IP platform, as well as the creation of commercial-quality prototypes of a novel biosensor platform which are presently undergoing market feedback in collaboration with commercial partners (and logical licensees) SimPore Inc. |
| Start Year | 2015 |
| Title | Nanostructured materials |
| Description | A novel nanoporous membrane and method of fabrication is taught, which confers an extremely sensitive surface enhanced Raman scattering (SERS)-based sensing substrate capable of large enhancements of Raman signatures of analytes bound to its surface. The material has the ability to perform flow-through sensing and is erasible using standard electrochemistry by virtue of its electrical contiguity. The material is fabricated using silicon wafer processing, lending itself to scalable and reproducible manufacture and solving a major barrier to the high-throughput fabrication of SERS sensors in the field. Licensing arrangements are under negotiation with SimPore Inc Rochester, NY and other parties via the University of Nottingham and University of Rochester technology transfer offices. |
| IP Reference | PCT 62/235 929 |
| Protection | Patent application published |
| Year Protection Granted | 2017 |
| Licensed | Commercial In Confidence |
| Impact | We have solved a major problem in the field - that of the scalable manufactur and reproducible enhancement factor associated with SERS-based measurements - allowing calibration, repeated usage, and erasible operating modes for SERS-based sensing platforms. |
| Title | PreFACE - Predictive Focus Automatic Correction Engine |
| Description | Presently under consideration for patent, funded by Cairn Research Ltd (Faversham, Kent), PreFACE is capable of extracting a focus error correction signal in real time from a single image with sub-micron accuracy for the closed-loop control of microscope focus during high-content screening and time-lapse assays. Patent relates to both software algorithm as well as hardware implementation. IP capture is being funded by industrial partner (Cairn) and commercialisation and licensing discussions are advanced between Cairn Research and the University of Nottingham tech transfer office. |
| IP Reference | |
| Protection | Copyrighted (e.g. software) |
| Year Protection Granted | |
| Licensed | Commercial In Confidence |
| Impact | PreFACE is being instrumented within the new high-content screening platform developed by ibidi GmbH (Munich) and will be released to the open-source microscopy community as a µManager plugin during Q4/18, following patent filing. A retrofittable product is under commercial development by Cairn Research Ltd for global sale in support of 3 out of 4 major microscopy manufacturers worldwide (Nikon, Olympus, Leica). |
| Title | PreFACE - Predictive Focus Automatic Correction Engine |
| Description | PreFACE is a novel image processing method capable of correcting the focus of a microscope imaging system indefinately in real time under closed-loop control. The underlying algorithm will be released to the open-source microscopy community as a µManager plugin in Q4/18 following patent filing, and will be sold in support of stand-alone imaging platforms (ibidi GmbH) and OEM components fitted to Nikon/Olympus/Leica microscope platforms. |
| Type Of Technology | Systems, Materials & Instrumental Engineering |
| Year Produced | 2017 |
| Impact | PreFACE will change the way that high-content and time-lapse imaging is performed across the world - presently a trade secret being developed for patent, the technology provides unprecedented functionality at extremely low cost, solving one of the crucial outstanding problems in the field - that of maintaining microscope focus for long periods under changing environmental conditions. |
| Description | Inaugural Symposium and Workshop - Epithelial Microdevices |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | an inaugural 3-day Symposium and workshop was held at the University of Rochester, NY on the theme of "Epithelial Microdevices". Participants were drawn from the UK, USA, and New Zealand and from several US states. Approximately 15 academics, 10 postgraduates and a similar number of undergraduates were brought together to focus on current themes in epithelial microdevices, with particular emphasis on the possiblities enabled by novel microporous and nanoporous membrane technologies and the ability to arbitrarily polarise epithelial tissues within devices and on surfaces. |
| Year(s) Of Engagement Activity | 2016 |