Thin Film Acoustic Wave Platform for Conformable and Mechanically Flexible Biosensors

Lead Research Organisation: Northumbria University
Department Name: Fac of Engineering and Environment

Abstract

In this project, we will research a new platform technology to manufacture flexible devices enabling non-invasive and rapid medical diagnostics. Due to global ageing and the increased burden of cancer/chronic diseases, there is a huge demand worldwide for efficient and inexpensive mobile healthcare, e-care, and home/point-of-care systems. These will not only be able to stop the cycle of transmission in infectious diseases, thus reducing their impact, but also allow us to monitor health conditions frequently (e.g. with wearable sensors) and tailor treatment as required, thus providing more efficient therapies. A key challenge for such devices is to integrate all the functions required to perform advanced diagnostics, such as sample manipulation, purification and sensing, onto a low-cost, mechanically flexible diagnostic/treatment platform, such that testing can be performed rapidly and frequently (for example in wearable patch applications). To be widely and effectively adopted, flexible diagnostics need to be conformable to diagnostic/treatment surfaces or to adapt to changes in surface shape (such as the human body), as well as to be compatible with large scale and low cost manufacturing technologies such as roll-to-roll/printing, whilst providing versatile integrated sampling/purification/sensing functions. These flexible and body comfortable sensors are becoming a promising route for new generations of personalised biomedical tools.

Here, we will use the mechanical energy propagated by acoustic waves on the surface of flexible foils, onto which we deposited a structured piezo-electric thin film. By controlling the orientation of the film, we will be able, for the first time, to integrate a large variety of fluid manipulation functions together with highly sensitive sensing, using a single technology. This will enable us to simplify design and manufacturing constraints significantly, leading to the potential of using large scale and low-cost manufacturing, drastically enhancing the availability and usefulness of personalised diagnostic devices. Our platform is based on versatile acoustic wave modes (integrating both microfluidics and sensing) compatible with roll-to-roll manufacturing and thin film/microfabrication technologies.

In the past decades, a large number of microfluidic and molecular sensing technologies have been developed based on integrated lab-on-chip, however only a few have been successfully introduced into the market, with one key reason for this attrition being that sampling (sample selection, collection and preparation, e.g., mixing, purification, filtering, washing, and then delivering to sensors) has not been successfully integrated into complete diagnosis systems in a simple, low-cost and efficient manner. In particular, there have been significant challenges in the integration of microfluidics (for sampling) with biosensing (detection) technologies, due to the different technologies that each function relies on, rendering the instrumentation too complex for truly portable and conformable systems. In this research, in partnership with industry, we will develop an innovative solution to integrate different acoustic modalities, which can provide different actuations of the sample (sampling, purification, sensing), using the formation of inclined angled ZnO thin films, such that we are able to generate and control different wave modes, i.e., longitudinal and shear waves on one platform. This will realise low-cost/flexible acoustic wave devices with integrated sensing and microfluidic functions.

Planned Impact

The ultimate benefit to society from the outcomes of this project will come through the provision of efficient and inexpensive mobile healthcare, e-care, and home/point-of-care systems, using an integrated and flexible acoustic wave platform. This platform will create impact through improvement in diagnosis and treatment of disease by solving the commonly-faced limitations linked with the complexity of automation of bio-sampling (from blood, saliva or other biological fluids) and highly sensitive sensing. This is critical for both the developed world (in primary care, point of care or in home diagnostics) and the developing world (with limited infrastructures or resources).

In the context of global ageing and an increasing burden of cancer/chronic diseases, these technologies will enable early diagnosis, with the potential to link to better outcomes, along with more frequent monitoring, leading to more efficient treatment regimes and better standard of living. By creating a mechanically flexible acoustic wave microfluidic platform for medical diagnostics with a non-invasive, low cost, mass production and roll-to-roll capability, we aim to impact on research, both academically and industrially, as well as more widely on the healthcare industry (with the provision of disposable diagnostic devices) and on society, providing better healthcare through enhanced disease diagnostics.

This research programme will provide technologies enabling decentralised medical diagnostics. The project demonstrator is focused on specific detection of inflammation markers, however, the integration of inclined thin film SAW technology onto flexible platform provides access to an extremely sensitive generic sensor technology with very broad applications. An important impact of the proposed research will be on relevant manufacturing sectors in the UK, including thin film based technology and microfabrication, and healthcare device manufacturing. The flexible medical diagnosis and healthcare sectors in UK and worldwide are rapidly growing, but presently still in their infancy, thus it is timely for researchers to establish a leading role. The impact of having a partnership with industry in this project will be to directly translate product concepts to product production, reducing the timescales of the inevitable iterative steps required in the development of any new process or technology. OJ-Bio is interested in extending their wireless sensing capability into flexible devices, and applying new types of enzymes and molecules to expand their application focus. Through its links to the market, Epigem will help the team accelerate the developments towards manufacturability, in particular with roll-to-roll and printing techniques.

The proposed work will also lead to the development of highly skilled multidisciplinary researchers (PDRAs) who can successfully deploy mobile health and point-of-care knowledge/techniques and facilitate its integration with both existing and new technologies and material systems. There is a great demand for these skills in the UK as well as throughout the world, with such individuals being particularly sought after in the growing health care and lab-on-chip manufacturing sectors where the majority of existing companies are SMEs.

The outputs from this project will be made available to the wider research community in the fields of biomedical diagnosis, lab-on-chip, microfluidics, thin film process, acoustic wave technology, microsystems manufacturing, through workshops, conference presentations and published papers. The successful dissemination and external implementation of the project outcomes will in turn drive forward the profile and relevance of manufacturing technologies, advanced materials, microsystems, sensors, biology, which are the key supported areas within EPSRC's remit.

Publications

10 25 50

 
Description We have achieved a flexible microfluidics devices, which can be rolled into a tube, which can pump the droplet on its surface. This flexible can be stretched back into flat shape, and can be further wrapped to other curved surfaces. This types of the flexible acoustic wave based lab-on-chip has never been achieved before. It could have significant applications in medicine, drug, and wound treatment applications.
Exploitation Route We have come up with some patented ideas and we will explore with local company to make into a product.
Sectors Electronics,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The project produced flexible lab-on-chip device, which has been discussed and arranged with a North-East local company, Epigem to do some commercialisation of bio-detection analysis tool. The products have been designed and developed at this stage. Epigem Company will explore for the commercialisation of the products for TB analysis.
First Year Of Impact 2017
Sector Electronics,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description Microfluidic nano-bio-chip for rapid and precision cancer diagnostics 
Organisation Harbin Institute of Technology
Country China 
Sector Academic/University 
PI Contribution The objective of this proposal is to design and fabricate a highly sensitive biodetection platform integrated with sampling functions (generation, mixing, transportation, enhanced reaction) from acoustic wave technology and precision sensing function based on graphene field-effect transistor (FET). The proposal builds upon the advanced materials, device design, fabrication and characterization technologies, with which two partners have leading expertise, and provides challenges in integrating acoustic wave microfluidics, graphene FET and biosensing of protein to realise a lab-on-chip platform. This proposal will provide technology enabling rapid diagnostics aiming for the point-of-cares and dealing with an ageing global population and the increasing importance of cancer/chronic diseases.
Collaborator Contribution The increase in demand for fast, cheap and sensitive bio-detection systems has been relentless, for applications such as point-of-care devices, rapid detections of contagious diseases, cancer or HIV. Many common procedures for biosensing or disease diagnosis based on DNA and protein technologies involve three main procedures: (1) sampling and transportation of fluid with DNA/protein into an area which has been pre-deposited with bio-molecules; (2) Mixing/reaction of the DNA/protein with oligonucleotide or antibody binders; (3) Detection of an associated change in physical, chemical, mechanical or electrical signals. The main challenge in developing such bio-detection systems is to find efficient and sensitive technologies which can fulfil the basic sampling, microfluidic and biosensing functions required for lab-on-a-chip systems, in order to reduce the device size and cost, and enhance sensing accuracy and performance (i.e., multiple disease detection). Recently Dr. Fu has been working on lab-on-chip to integrate microfluidics, piezoelectric thin film and surface acoustic wave (SAW) technologies, and successfully demonstrated to remotely manipulate liquids for efficient mixing, concentration, pumping, ejection, and biosensing functions. The acoustic wave can also be used for bio-sensing based on the fact that reaction of a small quantity of a target molecule with pre-deposited molecules leads to a shift in the resonant frequency. However, it has its intrinsic problems such as large noise to signal ratio and low sensitivity. On the other hand, Prof. Hu has been working on nano-biosensors based on field effect transistors (FETs) and demonstrated a highly sensitive biosensor based on carbon nanotube FETs. Recently he successfully demonstrated novel FETs using graphene as the electrode due to graphene's high carrier mobility, superior electrical conductivity and large specific surface area. However, there are no sampling and microfluidic functions associated with it. Clearly, there are rich rewards if these two technologies can be integrated to form a lab-on-chip with both microfluidics and bio-sensing for precision cancer detection, taking advantages of extensive experience of acoustic and MEMS technologies (Dr. Fu's group) and nano-biosensor using graphene FET (Prof. Hu's group).
Impact A few paper submissions in the revision process.
Start Year 2017
 
Description 1. 2018 - UK Fluids Network Special Interest Group on Acoustofluidics - Acoustofluidics Forum and Olympics (Northumbria University, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact 2018 - UK Fluids Network Special Interest Group on Acoustofluidics - Acoustofluidics Forum and Olympics (Northumbria University, UK) 26/4/18-27/10/18

Invited Research Talk - Droplets/Microfluidics on Smart Surfaces 26/4/18
Glen McHale
Year(s) Of Engagement Activity 2018
 
Description 2018 - 4th International Conference on Bioinspired and Biobased Chemistry & Materials (N.I.C.E. 2018) (Nice, France 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited/Keynote Research Talk - Droplets on Smart Slippery Surfaces 16/10/18
Glen McHale
Year(s) Of Engagement Activity 2018
URL http://www.unice.fr/nice-conference/
 
Description 2018 Institute of Physics NE Branch Public Understanding Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact 2018 Institute of Physics NE Branch Public Understanding Talk

Nature's Raincoats - Surface Inspiration from Lotus Leaves to Pitcher Plants (Northumbria University, UK) 26/10/18

Glen McHale
Year(s) Of Engagement Activity 2018
 
Description 2018 Public Understanding - "Nature's Raincoats" at the East Midlands Big Bang Fair (Derby, UK) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact 2018 Public Understanding - "Nature's Raincoats" at the East Midlands Big Bang Fair (Derby, UK) 28/06/ 2018
Physical exhibition with demonstrations
Year(s) Of Engagement Activity 2018
 
Description 2018 Seminar - Department of Mechanical Engineering at University of Bath (UK) 27th November 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact 2018 Seminar - Smart Super-Slippery Surfaces
Glen McHale
Year(s) Of Engagement Activity 2018
 
Description 2018 Seminar - Department of Mechanical Engineering at University of Glasgow (UK) 9th March 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact 2018 Seminar - From Superhydrophobic to Super-Slippery Surfaces
Glen McHale
Year(s) Of Engagement Activity 2018
 
Description 2019 Seminar - Department of Mechanical Engineering and Materials at University of Minnesota (Minneapolis, USA) 15th February 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact 2019 Seminar - From Superhydrophobic to Super-Slippery Surfaces
Glen McHale
Year(s) Of Engagement Activity 2019
 
Description Special Interest groups on Acoustofluidics 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Special interest group of Acoustofluidics is focused on phenomena and physics of acoustic waves interacting with liquid (either in droplet format or in micro-channels), and on engineering and applications of acoustofluidics in diagnostic systems, biotechnology and biomedicine. It will include topics of microfluidics induced by ultrasonic, surface acoustic waves, bulk acoustic waves and flexural waves, and use of these for bio-sampling, microanalysis, and microfluidic diagnosis.The aim of this first SIG meeting is for members of the SIG and other researchers
• To meet and understand each other's interests and capabilities,
• To update the latest research work on ultrasonic and acoustic wave based fluidics.
• To discuss about the funding opportunities, collaborations, student/research staff exchanges/visiting. On 25th May 2017. We had a pre-organiser chairmen meeting was held in the evening before the official group meeting. Dr. Richard Fu, Dr. Julien Reboud, Dr. Jeremy Hawkes, Prof. Jack Luo attended (with an invited guest Dr. Alex Yue from Univ West England). On 26th May 2017, we planned one-hour welcome tea/coffee time, and people introduced each other when they arrived and exchanged their research interests and areas. We started the meeting at 10:30am to provide people with enough time for traveling to Newcastle.
Prof. Glen McHale firstly introduced Northumbria University's research work , mainly focusing on fluidics and acoustofluidics using smart materials and smart surfaces structures. He also introduced themes of other three SIGs which are closely related to the SIG on Acoustofluidics, and discussed potential collaboration, exchange, student joint meeting, etc. The invited speaker, Prof. Martyn Hills from Southampton University, gave a review talk on ultrasonic microfluidics manipulation using standing waves, focusing on manipulation of biological cells and particles. This followed by the talk from invited speaker, Dr. Julien Reboud from Glasgow University, who gave a review on acoustofluidics based on surface acoustic waves (with all different biosampling functions which can be achieved) as well as integration with other technologies and methods for manipulation of particles and cells, PCR, lab-on-chip multiple functions. After a short discussion on the collaboration opportunities and organisation of future meetings, the group members went downstairs to take photos. The following photo includes only part of the attendants (as some of the others are still in the meeting room for discussions). After lunch, Prof. Jack Luo from Bolton University gave a talk on thin film based acoustofluidics and sensing system. He has explained the advantages using thin films instead of bulk materials and focused more on designs of biosensing platform, lab-on-chip and integrated systems. The representatives of about 12 group universities presented their research areas, facilities and capabilities, research groups, funding supports and recent developments, which are very useful for seeking the potential collaborations and funding. Here are a few selected photos from the presenters. After these talks, the group members were separated into small groups to discuss the future plans, funding opportunities, collaborations, student/research staff exchanges/visiting.
Year(s) Of Engagement Activity 2017
URL https://fluids.ac.uk/sig/Acoustofluidics
 
Description Sschool visit (Newcastle Schools students) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact This is an engaged activities as plan for the impact case study.
Year(s) Of Engagement Activity 2018