Film Bulk Acoustic Resonator-based Ultra-Sensitive Biosensor Array Using Low Cost Piezoelectric Polymer as the Active Material

Lead Research Organisation: University of Cambridge
Department Name: Engineering

Abstract

Biosensors are a type of microdevices that are able to measure very small concentration of biological molecules or chemical substances through specific bio-binding or chemical absorption. Biosensors are extremely useful in diagnosis, fighting terrorist and prevention of pandemic disease spread. Through detection of associated molecules such as DNA and antibody-antigen, they are very promising in early diagnosis of cancers and genetic disorder. Widespread applications of thus biosensors will lead to fast and accurate diagnosis, thus preventing unnecessary mortality and saving thousands of lives. Deployment of biosensors at key public locations enables detection of disease or biological substances in time, preventing spread of diseases or biochemical attach. High quality biosensors must be very sensitive, easy to use, low cost and fast with integrated electronics. Also multi-detection of many molecules using arrays is essential for reliable diagnosis and detection. Although many technologies have been developed such as microarrays and label-free electrochemical and optical biosensors. they have various shortages: lack of sensitivity and resolution, bulky and precise control of the sample position, or a large device size and lack of scalability etc. A multi-disciplinary team from Universities of Cambridge (CU), University of Manchester (MU) and University of Bolton (BU) is formed to develop a technology platform for biochemical detection using the most advanced film bulk acoustic wave resonator (FBAR) technology. FBAR device has a structure similar to quartz crystal microbalance but with a submicrometer thick piezoelectric (PE) active layer. It consists of a thin PE-layer with electrodes on both sides. Application of A.C. signals generates a standing wave between the two electrodes through PE effect. The resonant frequency is extremely sensitive to mass attached on the electrode surface owing to small device dimensions (thus the small base mass) and high operating frequency. Extremely small concentration of biomolecules can be detected through specific bio-binding with pre-deposited probe molecules on the electrode surface. The device has the combined merits of all other biosensors: label-free, ultra-high sensitivity and low detection limit, small dimensions, suitability for multi-detection using FBAR arrays, electronic output signal and low cost. The project will initially focus on development of high performance FBARs using piezoelectric (PE) ZnO thin films owing to its relatively mature technology. Biosensing technology will be developed in parallel using prostate-specific antigens (PSA) and peptide aptamers that specifically bind to those PSAs. Peptide aptamers have much better stability and specificity than proteins. Development of ZnO-based FBAR biosensors enables us to clarify all issues in device modelling, fabrication and characterisation, immobilization and biodetection etc. At the second stage, the project will develop novel FBARs on glass and plastic substrates using low cost PE-polymers. PE polymers such as polyvinylidene fluoride (PVDF) and its copolymer PVDF/TrFE have a piezoelectric constant and coupling coefficient comparable to the piezoelectric ceramics, and are biocompatible and chemically inert. Owing to their flexibility, it allows fabrication on low cost glass and plastic substrates. The cost of these biosensors will be extremely low. BU has excellent facilities for modelling and design, and for material and device characterisation. They will be responsible for modelling, design and characterisation. CU has a world-class cleanroom housed with excellent deposition, etch and microfabrication facilities. They will offer the expertise and experiences in device fabrication. The MU has first class biolab environment and relevant facilities for biological research. They are experts in protein adsorption, interfacial conformation, structural unfolding, and synthesis and cloning of peptide aptamers.

Publications

10 25 50

publication icon
García-Gancedo L (2013) Direct comparison of the gravimetric responsivities of ZnO-based FBARs and SMRs in Sensors and Actuators B: Chemical

publication icon
García-Gancedo L (2011) AlN-based BAW resonators with CNT electrodes for gravimetric biosensing in Sensors and Actuators B: Chemical

publication icon
García-Gancedo L (2012) Room-temperature remote-plasma sputtering of c -axis oriented zinc oxide thin films in Journal of Applied Physics

publication icon
García-Gancedo L (2011) ZnO-based FBAR resonators with carbon nanotube electrodes. in IEEE transactions on ultrasonics, ferroelectrics, and frequency control

publication icon
He X (2012) Film bulk acoustic resonator pressure sensor with self temperature reference in Journal of Micromechanics and Microengineering

publication icon
Nathan A (2012) Flexible Electronics: The Next Ubiquitous Platform in Proceedings of the IEEE

 
Description The overall aim of the proposed project was to develop an integrated biosensor array for disease detection and illness
diagnosis. The project was divided into four sub-goals: (1) to develop a technology to fabricate a highly sensitive FBAR
sensor which can be used as an universal sensing technology platform employing special bio-binding systems and
chemical absorption layers; (2) to develop a technology to fabricate low cost, high performance FBAR devices using a PE
polymer on a glass substrate; (3) develop a biorecognition system based-on peptide aptamers which has specific binding
ability with prostate-antigens, immobilization of biomolecules on the device surface and biodetection. (4) to characterize the
device performance and to verify its biodetection functionality using specific biochemical systems. To realize these goals,
the project has achieved a number of measurable objectives:
1. To optimize device structure and dimensions to obtain the best FBAR device performance. Models have been
established which enable simulation of the device performance taking into account of the influence of the electrode and
active layer thicknesses, material quality, surface roughness and attached biological species. (Objective unchanged and
completed)
2. To optimize the deposition of ZnO thin films for FBAR devices. Particular attention was paid to the requirement for
detection in liquid, meaning that a TSM FBAR is needed with off c-axis crystal orientation. In practice, the deposition of offaxis
material was not achieved. However, by using a novel HiTUS sputtering deposition technology for the ZnO, a far
better on-axis alignment of ZnO crystals was achieved which has led to devices being fabricated with a world-leading
quality (Q) factor (~2000).
3. To develop a technology to process high quality PE polymer thin films. The technology addressed the issues of thin film
formation, adhesion with the substrate, patterning, etching, poling to obtain the piezoelectric properties, and the excessive
damping on the "soft" substrates. Such devices were successfully manufactured and measured. The Q-factor of these
devices was, as expected, lower than that of the devices made with ZnO. Also, as the quality of the ZnO was far better
than expected (see objective #2) the focus of the project was shifted to concentrate more on the ZnO material.
4. To develop high sensitivity FBAR sensors using ZnO and PE polymers as the active layer with operation frequencies up
to 2 GHz. A technology was developed to fabricate biosensor arrays. (Objective unchanged and completed).
5. To develop a bio-recognition system which has a strong binding affinity and specificity with ability to retain biological
identities when bound with probe molecules. To develop a technology to deposit bio-probe molecules on the device surface
and a method to interrogate them to bind with target molecules for detection. (Objective unchanged and completed).
6. To characterize the FBAR device with PE ceramic and polymer thin films, and to develop a method to quantify the target
molecules bound with the probe molecules. And to develop a method for multi-channel parallel detection. In practice,
biological measurements were not made with the PE polymer as the ZnO devices were of significantly better quality than
expected.
7. To develop a technology for replacing metal electrodes on FBAR devices with carbon nanotube electrodes. This was a
new objective, which was completed successfully. The new devices show significantly improved performance due to the
reduced mass of the CNT electrodes (compared with metal) and the suppression of surface travelling waves, resulting in
enhanced Q-factor. We were the first group worldwide to propose, realise and publish such CNT electrode-based devices.
Overall, the result of this work has been that we lead the field in high sensitivity FBAR devices with a mass detection limit of
~1E-15g (approximately the mass of a single virus).
Exploitation Route The results are being used by a diversity of industries with a requirement for physical or biological sensing. The University of Cambridge is licensing the IP associated with this project to a new spin-out, Sorex Sensors Ltd.
Sectors Agriculture, Food and Drink,Chemicals,Electronics,Environment,Healthcare

 
Description The results of this project havce been used to significantly advcance the use of film bulk acoustic resonator devices for a range of sensing applications, including in the biological sensing and physical sensing fields. It has resulted in sevela follow-on projects and collaborations with a number of industry partners. It has also resulted in a patent application that has been filed in Europe, the USA and Korea
First Year Of Impact 2012
Sector Chemicals,Electronics,Healthcare
Impact Types Economic

 
Description Cancer Research UK Cambridge Centre Early Detection 2015
Amount £61,656 (GBP)
Organisation Cambridge Cancer Centre 
Sector Academic/University
Country United Kingdom
Start 04/2016 
End 10/2017
 
Description EPSRC
Amount £22,065 (GBP)
Funding ID Cambridge University Knowledge Transfer - Pathways to I 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 01/2012 
End 06/2012
 
Description European Commission Research Directorate
Amount £490,015 (GBP)
Funding ID CP-IP 246334-2 
Organisation European Commission 
Department Directorate General for Research and Innovation
Sector Public
Country European Union (EU)
Start 10/2010 
End 09/2014
 
Description H2020 - H2020-SPIRE-2014
Amount € 888,270 (EUR)
Funding ID 636820 
Organisation European Commission 
Department Horizon 2020
Sector Public
Country European Union (EU)
Start 01/2015 
End 12/2017
 
Description Knowledge Transfer Partnership
Amount £101,539 (GBP)
Funding ID KTP010131 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 05/2016 
End 04/2018
 
Company Name Sorex Sensors Limited 
Description Sorex Sensors Limited aim to commercialise film bulk acoustic resonator technology for gravimetric sensing applications. 
Year Established 2017 
Impact None as yet.
Website http://sorexsensors.com/