Biofilm Activity Analyser for Healthcare Applications
Lead Research Organisation:
University of Warwick
Department Name: Chemistry
Abstract
In this feasibility study, work will be carried out by Warwick in order to develop a biocompatible diamond based biofilm activity analyser, which is capable of placement within the small, non-disposable plastic tubing associated with the waterlines of dental unit water systems (DUWS's) and internal tubing of dialysis machines. Biofilm build-up is a huge problem as if left unchecked can led to potential life-threatening bacterial infections in the patient, particularly problematic with those already suffering from illness. The sensor will be designed to monitor biofilm growth continuously, based on electrochemical principles. The initial part of the research undertaken at Warwick will be to design an appropriate sensor geometry which is both small enough to fit into the associated tubing but also has the sensitivity to detect and monitor biofilm build-up on the sensor surface. Additional capabilities, such as the ability of the sensor to clean itself, will also be built in. Using personnel at Warwick, skilled in the art of processing diamond materials, inverse electrode structures will be laser machined into sheets of insulating diamond. The diamond will then be sent for conducting diamond overgrowth, and then be returned to Warwick for highly specialised polishing to produce co-planar insulating-conducting diamond structures (the sensor). The sensor will then be electrically contacted and test rigs at Warwick built which replicate the water /dialysate environments of DUWS's and dialysis units. The sensor(s) performance (in terms of an output current) will be monitored continuously and the sensor periodically assessed to ascertain the extent of biofilm build-up on the surface. Simultaneous measurements of microbial content in the water will also be taken. This is in order to relate extent of biofilm build up to numbers of colony forming units, such that it is possible to programme the sensor to notify the user when biofilm activity has risen above a "safe" level.
Technical Summary
In this feasibility study, work will be carried out by Warwick in order to develop a biocompatible diamond based biofilm activity analyser, which is capable of placement within the small, non-disposable plastic tubing associated with the waterlines of dental unit water systems (DUWS's) and internal tubing of dialysis machines. Biofilm build-up is a huge problem as if left unchecked can led to potential life-threatening bacterial infections in the patient, particularly problematic with those already suffering from illness. The sensor will be designed to monitor biofilm growth continuously, based on electrochemical principles. The initial part of the research undertaken at Warwick will be to design an appropriate sensor geometry which is both small enough to fit into the associated tubing but also has the sensitivity to detect and monitor biofilm build-up on the sensor surface. Additional capabilities, such as the ability of the sensor to clean itself, will also be built in. Using personnel at Warwick, skilled in the art of processing diamond materials, inverse electrode structures will be laser machined into sheets of insulating diamond. The diamond will then be sent for conducting diamond overgrowth, and then be returned to Warwick for highly specialised polishing to produce co-planar insulating-conducting diamond structures (the sensor). The sensor will then be electrically contacted and test rigs at Warwick built which replicate the water /dialysate environments of DUWS's and dialysis units. The sensor(s) performance (in terms of an output current) will be monitored continuously and the sensor periodically assessed to ascertain the extent of biofilm build-up on the surface. Simultaneous measurements of microbial content in the water will also be taken. This is in order to relate extent of biofilm build up to numbers of colony forming units, such that it is possible to programme the sensor to notify the user when biofilm activity has risen above a "safe" level.
Planned Impact
The most immediate impact of the feasibility study will be on improvements to patient safety during dental and renal healthcare. With a lack of continuous monitoring, and recognised testing procedures involving bacterial culturing of the water systems taking at least several days to complete, bacterial levels in the water pipes of dental waterlines and renal dialysis units can rise above recommended safety levels during patient treatment. This obviously impacts on patient well-being, more especially so for patients already compromised by illness, as in the case of e.g. renal failure patients.
Moreover, the treatment procedures adopted to clean the systems involves flushing with chemically unfriendly biocides. However, with no immediate feedback on efficacy, too much or too little can be administered. Too little, results in compromises to patient well-being and too much results in unnecessary use of potentially harmful chemicals. In contrast, continuous monitoring using our sensor, enables the right dose to be applied at the right time. Ultimately if the feasibility tests are successful, development of the proposed biofilm sensor, at a commercially viable cost, would result in take up by the international community and capture of a portion of a world-wide market share for a UK-based consortium. This in itself would also impact on job creation in a regionally deprived area; the industrial collaborating SME, Process Instruments is based in the North of England (Burnley).
Although the target market is sizeable, the diamond sensor technology is highly likely to have additional applications directly in biofilm monitoring in other water applications, such as potable water supply, swimming pools, heating/cooling water systems etc. Indirectly, the diamond also provides an ideal platform for the development of other sensors where chemical species monitoring in harsh environments, where diamond wins out over other electrochemical based sensors, is required. The diamond BAA sensor technology is thus expected to impact on, and underpin, a wide variety of applications and technologies that will be unlocked by Innovate UK Biofilm feasibility funding. All parties are committed to developing the diamond sensor technology. A successful feasibility study would also provide the necessary results to galvanise interactions between Process Instruments and both healthcare clinicians and providers of renal dialysis machines and dental unit water systems, in order to encourage take-up.
The biofilm sensor technology will also impact directly on the academic community. Through papers and conference presentations, given during this project, the academic community will be familiarised with developments made in miniaturised diamond biofilm sensing technologies (and related activities). This will act as a stimulant for future research and development into the use of such sensing platforms for a wide variety of different chemical species. This will pave the way for a new generation of diamond based electrochemical sensing devices both in the laboratory and in the commercial world.
Moreover, the treatment procedures adopted to clean the systems involves flushing with chemically unfriendly biocides. However, with no immediate feedback on efficacy, too much or too little can be administered. Too little, results in compromises to patient well-being and too much results in unnecessary use of potentially harmful chemicals. In contrast, continuous monitoring using our sensor, enables the right dose to be applied at the right time. Ultimately if the feasibility tests are successful, development of the proposed biofilm sensor, at a commercially viable cost, would result in take up by the international community and capture of a portion of a world-wide market share for a UK-based consortium. This in itself would also impact on job creation in a regionally deprived area; the industrial collaborating SME, Process Instruments is based in the North of England (Burnley).
Although the target market is sizeable, the diamond sensor technology is highly likely to have additional applications directly in biofilm monitoring in other water applications, such as potable water supply, swimming pools, heating/cooling water systems etc. Indirectly, the diamond also provides an ideal platform for the development of other sensors where chemical species monitoring in harsh environments, where diamond wins out over other electrochemical based sensors, is required. The diamond BAA sensor technology is thus expected to impact on, and underpin, a wide variety of applications and technologies that will be unlocked by Innovate UK Biofilm feasibility funding. All parties are committed to developing the diamond sensor technology. A successful feasibility study would also provide the necessary results to galvanise interactions between Process Instruments and both healthcare clinicians and providers of renal dialysis machines and dental unit water systems, in order to encourage take-up.
The biofilm sensor technology will also impact directly on the academic community. Through papers and conference presentations, given during this project, the academic community will be familiarised with developments made in miniaturised diamond biofilm sensing technologies (and related activities). This will act as a stimulant for future research and development into the use of such sensing platforms for a wide variety of different chemical species. This will pave the way for a new generation of diamond based electrochemical sensing devices both in the laboratory and in the commercial world.
People |
ORCID iD |
| Julie MacPherson (Principal Investigator) |
| Description | Studies have shown that a real risk exists to the health of dental and renal patients due to infections derived from bacteria present in the water used during treatment and these infections are directly associated with the growth of biofilm in the water lines. The health care industry has expended much effort in disinfecting the water used in dental procedures and dialysis units but there is no online method of measuring the efficiency of that disinfection with regard to its ability to prevent or remove biofilm growth. This project aimed to provide a new Biofilm Activity Analyser (BAA) sensor which is placed directly in the small plastic tubing of the dental unit water system and dialysis unit, is biocompatible, and capable of extended operation. The miniaturisation of the sensor to enable continuous monitoring of biofilm in small water lines of less than 8mm diameter provided technical risk. During the project specialist circuitry to measure the tiny signals the sensor produced had to be developed. New software algorithms were created to analyse the measurements and provide an indication of biofilm activity. Using this circuitry and software, the sensor is able to integrate with a commercially available analyser that can record data and issue alarm notifications when biofilm growth is detected. Many materials of construction were considered, some novel and required new manufacturing methods. Three designs were chosen to build and trial: a) A sensor consisting of consecutive rings of conducting electrodes and insulating bands. The water sample flows through the tube constructed by this arrangement. The materials used were conducting (carbon fibre loaded) and insulating polymers in an additive manufacturing process. This option is relatively low cost. b) A screen-printed electrode array using conductive inks. This sensor is lowest cost but designed to be disposable when biofilm is detected. c) A design of interdigitating electrodes of boron-doped diamond (BDD) encapsulated in a background of insulating diamond. BDD is a novel electrode material suitable for this application as it is able to withstand the harsh chemical environment associated with the biofilm cleaning procedures without requiring replacement or recalibration. The electrode is manufactured by first growing an unmodified diamond substrate. Trenches are then laser ablated into this substrate before overgrowth of diamond in an environment with controlled concentrations of boron. The boron is incorporated in to the growing diamond lattice making the BDD electrically conductive. The substrate is polished to reveal the original trench structure filled with BDD. A feasibility study using distilled water controls and feeds from bioreactors quickly ruled out sensor designs a) and b) as the results they produced where too noisy to discern biofilm growth events. The screen-printed electrodes also degraded too quickly to be of economical use. The BDD structures, however, gave clear signals with low noise that were able to distinguish biofilm growth. The manufacturing process for the BDD sensor was deemed to be too expensive, and the sensor design changed to use lower cost commercially available material. Wafers of electrochemical grade BDD where cut in to strips and embedded in an epoxy mould. This lower cost design gave consistent measurements with the encapsulated diamond design, achieving the key project aim. |
| Exploitation Route | Work will need to continue with further feasibility studies to understand the biofilm attachment process to the sensor in order to improve sensitivity. The signals generated by the sensor will need to be further analysed to determine a more robust biofilm detection algorithm. If successful it is expected this project will deliver high growth and jobs for a UK supply chain within five years; with the biofilm monitors fabricated, packaged, assembled and tested in the UK. The high value of the sensor and electronics result in it being a viable UK manufacturing activity. The jobs (estimated at up to 15, both direct and indirect in the supply chain) will be high value and largely in the North of England. |
| Sectors | Environment,Healthcare |
| Description | We successfully produced a prototype miniaturised biofilm activity sensor capable of producing current signals which alert to the presence of a growing biofilm - this prototype will be further developed by the collaborating SME, Process Instruments (Pi) - leading to job creation and commercial impact |
| First Year Of Impact | 2017 |
| Sector | Environment |
| Impact Types | Economic |
| Description | EU RESEARCH FRAMEWORK PROGRAMME: H2020 / Marie Sklodowska-Curie Actions |
| Amount | € 4,033,858 (EUR) |
| Funding ID | BREAK BIOFILMS Grant agreement ID: 813439 |
| Organisation | EU-T0 |
| Sector | Public |
| Country | European Union (EU) |
| Start | 09/2019 |
| End | 09/2022 |
| Description | Royal Society Innovation Award |
| Amount | £250,000 (GBP) |
| Organisation | The Royal Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2017 |
| End | 05/2019 |