Microelectronics-Based Biosensors Dedicated to the Detection of Neurotransmitters: A Review

Dysregulation of neurotransmitters (NTs) in the human body are related to diseases such as Parkinson's and Alzheimer's. The mechanisms of several neurological disorders, such as epilepsy, have been linked to NTs. Because the number of diagnosed cases is increasing, the diagnosis and treatment of such diseases are important. To detect biomolecules including NTs, microtechnology, micro and nanoelectronics have become popular in the form of the miniaturization of medical and clinical devices. They offer high-performance features in terms of sensitivity, as well as low-background noise. In this paper, we review various devices and circuit techniques used for monitoring NTs in vitro and in vivo and compare various methods described in recent publications

Biocompatible low-cost CMOS electrodes for neuronal interfaces, cell impedance and other biosensors

The adaptation of standard integrated circuit (IC) technology for biosensors in drug discovery pharmacology, neural interface systems, environmental sensors and electrophysiology requires electrodes to be electrochemically stable, biocompatible and affordable. Unfortunately, the ubiquitous IC technology, complementary metal oxide semiconductor (CMOS), does not meet the first of these requirements. For devices intended only for research, modification of CMOS by post-processing using cleanroom facilities has been achieved by others. However, to enable adoption of CMOS as a basis for commercial biosensors, the economies of scale of CMOS fabrication must be maintained by using only low-cost post-processing techniques. The scope of this work was to develop post-processing methods that meet the electrochemical and biocompatibility requirements but within the low-cost constraint. Several approaches were appraised with the two most promising designs taken forward for further investigation. Firstly, a process was developed whereby the corrodible aluminium is anodised to form nanoporous alumina and further processed to optimise its impedance. A second design included a noble metal in the alumina pores to enhance further the electrical characteristics of the electrode. Experiments demonstrated for the first time the ability to anodise CMOS metallisation to form the desired electrodes. Tests showed the electrode addressed the problems of corrosion and presented a surface that was biocompatible with the NG108-15 neuronal cell line. Difficulties in assessing the influence of alumina porosity led to the development of a novel cell adhesion assay that showed for the first time neuronal cells adhere preferentially to large pores rather than small pores or planar aluminium. It was also demonstrated that porosity can be manipulated at room temperature by modifying the anodising electrolyte with polyethylene glycol. CMOS ICs were designed as multiple electrode arrays and optimised for neuronal recordings. This utilised the design incorporating a noble metal deposited into the porous alumina. Deposition of platinum was only partially successful, with better results using gold. This provided an electrode surface suitable for electric cell-substrate impedance sensors (ECIS) and many other sensor applications. Further processing deposited platinum black to improve signal-to-noise ratio for neuronal recordings. The developed processes require no specialised semiconductor fabrication equipment and can process CMOS ICs on laboratory or factory bench tops in less than one hour. During the course of electrode development, new methods for biosensor packaging were assessed: firstly, a biocompatible polyethylene glycol mould process was developed for improved prototype assembly. Secondly, a commercial ‘partial encapsulation’ process (Quik-Pak, U.S.) was assessed for biocompatibility. Cell vitality tests showed both methods were biocompatible and therefore suitable for use in cell-based biosensors. The post-processed CMOS electrode arrays were demonstrated by successfully recording neuronal cell electrical activity (action potentials) and by ECIS with a human epithelial cell line (Caco2). It is evident that these developments may provide a missing link that can enable commercialisation of CMOS biosensors. Further work is being planned to demonstrate the technology in context for specific markets.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A basic review of integrated circuits and fabrication

Abstract: This paper provides the review of how integrated circuits have dominated the market, changing trends in its development and research work conducted in the field of integrated circuits

Integrated circuit & system design for concurrent amperometric and potentiometric wireless electrochemical sensing

Complementary Metal-Oxide-Semiconductor (CMOS) biosensor platforms have steadily grown in healthcare and commerial applications. This technology has shown potential in the field of commercial wearable technology, where CMOS sensors aid the development of miniaturised sensors for an improved cost of production and response time. The possibility of utilising wireless power and data transmission techniques for CMOS also allows for the monolithic integration of the communication, power and sensing onto a single chip, which greatly simplifies the post-processing and improves the efficiency of data collection. The ability to concurrently utilise potentiometry and amperometry as an electrochemical technique is explored in this thesis. Potentiometry and amperometry are two of the most common transduction mechanisms for electrochemistry, with their own advantages and disadvantages. Concurrently applying both techniques will allow for real-time calibration of background pH and for improved accuracy of readings. To date, developing circuits for concurrently sensing potentiometry and amperometry has not been explored in the literature. This thesis investigates the possibility of utilising CMOS sensors for wireless potentiometric and amperometric electrochemical sensing. To start with, a review of potentiometry and amperometry is evaluated to understand the key factors behind their operation. A new configuration is proposed whereby the reference electrode for both electrochemistry techniques are shared. This configuration is then compared to both the original configurations to determine any differences in the sensing accuracy through a novel experiment that utilises hydrogen peroxide as a measurement analyte. The feasibility of the configuration with the shared reference electrode is proven and utilised as the basis of the electrochemical configuration for the front end circuits. A unique front-end circuit named DAPPER is developed for the shared reference electrode topology. A review of existing architectures for potentiometry and amperometry is evaluated, with a specific focus on low power consumption for wireless applications. In addition, both the electrochemical sensing outputs are mixed into a single output data channel for use with a near-field communication (NFC). This mixing technique is also further analysed in this thesis to understand the errors arising due to various factors. The system is fabricated on TSMC 180nm technology and consumes 28µW. It measures a linear input current range from 250pA - 0.1µW, and an input voltage range of 0.4V - 1V. This circuit is tested and verified for both electrical and electrochemical tests to showcase its feasibility for concurrent measurements. This thesis then provides the integration of wireless blocks into the system for wireless powering and data transmission. This is done through the design of a circuit named SPACEMAN that consists of the concurrent sensing front-end, wireless power blocks, data transmission, as well as a state machine that allows for the circuit to switch between modes: potentiometry only, amperometry only, concurrent sensing and none. The states are switched through re-booting the circuit. The core size of the electronics is 0.41mm² without the coil. The circuit’s wireless powering and data transmission is tested and verified through the use of an external transmitter and a connected printed circuit board (PCB) coil. Finally, the future direction for ongoing work to proceed towards a fully monolithic electrochemical technique is discussed through the next development of a fully integrated coil-on-CMOS system, on-chip electrodes with the electroplating and microfludics, the development of an external transmitter for powering the device and a test platform. The contributions of this thesis aim to formulate a use for wireless electrochemical sensors capable of concurrent measurements for use in wearable devices.Open Acces

Digital CMOS ISFET architectures and algorithmic methods for point-of-care diagnostics

Over the past decade, the surge of infectious diseases outbreaks across the globe is redefining how healthcare is provided and delivered to patients, with a clear trend towards distributed diagnosis at the Point-of-Care (PoC). In this context, Ion-Sensitive Field Effect Transistors (ISFETs) fabricated on standard CMOS technology have emerged as a promising solution to achieve a precise, deliverable and inexpensive platform that could be deployed worldwide to provide a rapid diagnosis of infectious diseases. This thesis presents advancements for the future of ISFET-based PoC diagnostic platforms, proposing and implementing a set of hardware and software methodologies to overcome its main challenges and enhance its sensing capabilities. The first part of this thesis focuses on novel hardware architectures that enable direct integration with computational capabilities while providing pixel programmability and adaptability required to overcome pressing challenges on ISFET-based PoC platforms. This section explores oscillator-based ISFET architectures, a set of sensing front-ends that encodes the chemical information on the duty cycle of a PWM signal. Two initial architectures are proposed and fabricated in AMS 0.35um, confirming multiple degrees of programmability and potential for multi-sensing. One of these architectures is optimised to create a dual-sensing pixel capable of sensing both temperature and chemical information on the same spatial point while modulating this information simultaneously on a single waveform. This dual-sensing capability, verified in silico using TSMC 0.18um process, is vital for DNA-based diagnosis where protocols such as LAMP or PCR require precise thermal control. The COVID-19 pandemic highlighted the need for a deliverable diagnosis that perform nucleic acid amplification tests at the PoC, requiring minimal footprint by integrating sensing and computational capabilities. In response to this challenge, a paradigm shift is proposed, advocating for integrating all elements of the portable diagnostic platform under a single piece of silicon, realising a ``Diagnosis-on-a-Chip". This approach is enabled by a novel Digital ISFET Pixel that integrates both ADC and memory with sensing elements on each pixel, enhancing its parallelism. Furthermore, this architecture removes the need for external instrumentation or memories and facilitates its integration with computational capabilities on-chip, such as the proposed ARM Cortex M3 system. These computational capabilities need to be complemented with software methods that enable sensing enhancement and new applications using ISFET arrays. The second part of this thesis is devoted to these methods. Leveraging the programmability capabilities available on oscillator-based architectures, various digital signal processing algorithms are implemented to overcome the most urgent ISFET non-idealities, such as trapped charge, drift and chemical noise. These methods enable fast trapped charge cancellation and enhanced dynamic range through real-time drift compensation, achieving over 36 hours of continuous monitoring without pixel saturation. Furthermore, the recent development of data-driven models and software methods open a wide range of opportunities for ISFET sensing and beyond. In the last section of this thesis, two examples of these opportunities are explored: the optimisation of image compression algorithms on chemical images generated by an ultra-high frame-rate ISFET array; and a proposed paradigm shift on surface Electromyography (sEMG) signals, moving from data-harvesting to information-focused sensing. These examples represent an initial step forward on a journey towards a new generation of miniaturised, precise and efficient sensors for PoC diagnostics.Open Acces

Organic electronics for neuromorphic computing

Neuromorphic computing could address the inherent limitations of conventional silicon technology in dedicated machine learning applications. Recent work on silicon-based asynchronous spiking neural networks and large crossbar-arrays of two-terminal memristive devices has led to the development of promising neuromorphic systems. However, delivering a compact and efficient parallel computing technology, such as artificial neural networks embedded in hardware, remains a significant challenge. Organic electronic materials offer an attractive alternative for such systems and could provide biocompatible and relatively inexpensive neuromorphic devices with low-energy switching and excellent tunability. Here, we review the development of organic neuromorphic devices. We consider different resistance switching mechanisms, which typically rely on electrochemical doping or charge trapping, and discuss the challenges the field faces in implementing low power neuromorphic computing, which include device downscaling, improving device speed, state retention and array compatibility. We highlight early demonstrations of device integration into arrays and finally consider future directions and potential applications of this technology

INTEGRATION OF CMOS TECHNOLOGY INTO LAB-ON-CHIP SYSTEMS APPLIED TO THE DEVELOPMENT OF A BIOELECTRONIC NOSE

This work addresses the development of a lab-on-a-chip (LOC) system for olfactory sensing. The method of sensing employed is cell-based, utilizing living cells to sense stimuli that are otherwise not easily sensed using conventional transduction techniques. Cells have evolved over millions of years to be exquisitely sensitive to their environment, with certain types of cells producing electrical signals in response to stimuli. The core device that is introduced here is comprised of living olfactory sensory neurons (OSNs) on top of a complementary metal-oxide-semiconductor (CMOS) integrated circuit (IC). This hybrid bioelectronic approach to sensing leverages the sensitivity of OSNs with the electronic signal processing capability of modern ICs. Intimately combining electronics with biology presents a number of unique challenges to integration that arise from the disparate requirements of the two separate domains. Fundamentally the obstacles arise from the facts that electronic devices are designed to work in dry environments while biology requires not only a wet environment, but also one that is precisely controlled and non-toxic. Design and modeling of such heterogeneously integrated systems is complicated by the lack of tools that can address the multiple domains and techniques required for integration, namely IC design, fluidics, packaging, and microfabrication, and cell culture. There also arises the issue of how to handle the vast amount of data that can be generated by such systems, and specifically how to efficiently identify signals of interest and communicate them off-chip. The primary contributions of this work are the development of a new packaging scheme for integration of CMOS ICs into fluidic LOC systems, a methodology for cross-coupled multi-domain iterative modeling of heterogeneously integrated systems, demonstration of a proof-of-concept bioelectronic olfactory sensor, and a novel event-based technique to minimize the bandwidth required to communicate the information contained in bio-potential signals produced by dense arrays of electrically active cells

Alternative Electrode Materials for Prototyping Cell Model-Specific Microelectrode Arrays

Mikroelektrodimatriisi (MEA, microelectrode array) on biologien käyttämä väline solujen sähköisen toiminnan mittaamiseen in vitro olosuhteissa. Pelkkien satunnaisten soluryppäiden ja yksikerroksisten soluviljelmien tutkimisen rinnalla yleistymässä ovat biologiset tutkimuskysymykset, joissa tutkitaan ohjatusti muodostettuja soluverkkoja tai yksittäisiä soluja. Nämä aiheet asettavat sellaisia erityisvaatimuksia elektrodien koolle ja sijainnille MEA-levyllä, sekä ylipäätään MEA-levyn suorituskyvylle, että kaupasta saatavat vakiomalliset MEA-levyt eivät yleensä niitä täytä. Räätälöidyille MEA-levyille onkin tarvetta monella sovellusalueella perussolubiologiasta ja tautimallien kehittämisestä myrkyllisyystutkimuksiin ja lääketestaukseen. Tässä väitöstyössä on valmistettu mikroelektrodeja, joiden materiaalina on käytetty titaania, atomikerroskasvatettua (atomic layer deposition, ALD) iridiumoksidia (IrOx) sekä ionisuihkuavusteiselle elektronisuihkuhöyrystyksellä (ion beam assisten e-beam deposition, IBAD) tuotettua titaaninitridiä (TiN). Elektrodit on karakterisoitu mm. niiden impedanssin, kohinatason ja pinnan morfologian osalta. Lisäksi bioyhteensopivuus ja toimivuus on varmistettu kokeilla, joissa on käytetty ihmisperäisistä kantasoluista johdettuja hermo- ja sydänsoluja. Näiden tutkimusten tarkoituksena on tarjota MEA-valmistukseen lisää vaihtoehtoja, mistä valita eri sovelluksiin parhaiten sopivat ja käytettävissä olevat resurssit parhaiten huomioivat elektrodimateriaalit. Titaanin käyttöä puhtaasti metallimuodossa on mikroelektrodimateriaalina yleisesti vältetty sen johtavuusominaisuuksia häiritsevän hapettumistaipumuksen vuoksi. Valmistukseen kuluva aika ja kustannukset voivat kuitenkin olla räätälöityjen MEA-prototyyppien kehittämisessä olennaisempia tekijöitä kuin prototyypin huippuunsa viritetty suorituskyky, jota usein arvioidaan 1 kHz taajuudella mitatun impedanssin avulla. Kuten odotettua, titaanielektrodien impedanssi oli huomattavan korkea (>1700 kΩ), mutta silti solumittauksissa sekä hermo- että sydänsolujen tuottamat kenttäpotentiaalisignaalit olivat erotettavissa kohinasta. Titaanin etuihin elektrodimateriaalina kuuluvat yleisimpiin vaihtoehtoihin verrattuna vähäisempien ja yksinkertaisempien prosessivaiheiden tarve sekä noin sata kertaa pienemmät raaka-aine kustannukset kultaan ja platinaan verrattuna. IrOx ja TiN ovat yleisesti käytettyjä elektrodien pinnoitusmateriaaleja, joiden tarkoitus on laskea esimerkiksi titaanista tehtyjen elektrodien impedanssia ja kohinatasoa. Tässä työssä tutkittiin mahdollisuutta tehdä pinnoitukset vaihtoehtoisilla, MEA sovelluksissa uusilla menetelmillä, ALD:llä ja IBAD:lla. Vaikka näillä menetelmillä pinnoitettujen 30 μm elektrodien impedanssit (450 kΩ ALD IrOx:lle ja ~90 kΩ IBAD TiN:lle) eivät aivan laskeneetkaan yleisesti käytettyjen sputteroidun TiN:n (30-50 kΩ) ja huokoisen platinan eli Pt black:n (20-30 kΩ) tasolle, niin solumittauksissa etenkään IBAD TiN elektrodien ja sputteroitujen TiN elektrodien välillä ei ollut käytännössä lainkaan havaittavaa eroa kohinatasossa ja signaalipiikkien korkeuksissa. Täten IBAD TiN onkin täysin varteenotettava materiaalivaihtoehto niille, jotka suosivat TiN elektrodeja, mutta joilla ei ole sputteriointiin sopivaa laitetta käytettävissä. ALD:n ja IrOx:n yleiset ominaisuudet sen sijaan puoltavat ALD IrOx:n sopimista erityisesti geometrialtaan haastaviin tapauksiin tai sovelluksiin, joissa elektrodeilta vaaditaan erinomaisia stimulointiominaisuuksia. Lopuksi tässä väitöstyössä kehitettiin esimerkkinä räätälöidyn MEA-levyn vaativasta sovelluksesta yksittäisten sydänsolujen mittaamiseen soveltuva MEA-levy. Tällainen MEA-levy tarjoaa yleisesti käytetylle, mutta työläälle patch-clamp menetelmälle ainutlaatuisen soluja vahingoittamattoman vaihtoehdon yksittäisten solujen tutkimiseksi, sekä mahdollistaa yksittäisen solun ominaisuuksien havainnoinnin paremmin, kuin usein varsin heterogeenisen soluviljelmän tutkiminen vakiomallisella MEA-levyllä. Ratkaisuna tähän oli elektrodien sijoittaminen lähelle solualueen ulkokehää sekä elektrodien halkaisijan kasvattaminen 80 μm:iin tavanomaisesta 30 μm:stä, mikä helpotti solujen asettamista elektrodeille ja mahdollisti solujen sähköisen sykesignaalin mittaamisen. Indiumtinaoksidi (ITO) elektrodien läpinäkyvyys mahdollisti lisäksi mekaanisen sykinnän analysoimisen kuvaan perustuvan mittaamisen avulla.A microelectrode array, MEA, is a tool used by biologists for measuring the electrical activity of cells in vitro. Instead of only studying random cell clusters and monolayers, an increasing number of biological research questions are aimed at studying well- defined cell networks or single cells. This places special demands on the location, size, and overall performance of the MEA electrodes, which the standard, commercially available layouts cannot usually meet. Therefore, custom-designed MEAs are needed for a wide range of applications from basic cell biology and disease model development to toxicity testing and drug screening. This thesis focuses on the fabrication of microelectrodes made of titanium, atomic layer deposited (ALD) iridium oxide (IrOx), and ion beam-assisted e-beam deposited (IBAD) titanium nitride (TiN). These MEAs are characterized, for example, in terms of their impedance, noise level, and surface morphology, and their biocompatibility and functionality are verified by simple experiments with human stem cell-derived neuronal cells and cardiomyocytes. The aim of these studies is to offer more alternatives for MEA fabrication, enabling researchers and practitioners to choose the electrode material that best fits their application from their available resources. Pure titanium is commonly disregarded as an electrode material because of its oxidation tendency, which destabilizes the electrical performance. However, when prototyping customised MEAs, the time and cost of fabricating the subsequent iterations of the prototype can be more decisive factors than the device’s ultimate electrical performance, which is typically evaluated by the impedance value at 1 kHz. As might be expected, although titanium electrodes underperformed in terms of impedance (>1700 kΩ), when used in the cell experiments, the field potentials from both neuronal cells and cardiomyocytes were still easily distinguishable from the noise. There are a number of benefits to using titanium as an electrode material. Besides the fact that it is about hundred times cheaper than other commonly-used materials, such as gold or platinum, it usually requires fewer and often simpler process steps than the most common alternatives. IrOx and TiN are common electrode coatings which, when applied on top of e.g. a titanium electrode, can lower the impedance and the noise level of the electrode. In this study, two alternative deposition methods, ALD and IBAD, were used for IrOx and TiN in MEA applications. Even if the impedance of these 30 μm electrodes (450 kΩ for ALD IrOx and ~90 kΩ for IBAD TiN) did not quite reach the impedance levels of the industry standards, i.e. sputtered TiN (30-50 kΩ) and Pt black (20-30 kΩ), in cell experiments the IBAD TiN electrodes in particular showed no tangible differences in peak amplitudes and noise levels compared with sputtered TiN electrodes. This makes IBAD TiN an attractive alternative material for those who prefer to use TiN electrodes, but do not have access to a sputter coater, for example. ALD IrOx, on the other hand, relies on the potential of the general properties of ALD and IrOx (yet unverified) to provide exceptional performance in designs requiring excellent step coverage or stimulation capability. Finally, as an application example of a custom-designed MEA, a version capable of measuring cardiomyocytes at the single-cell level was developed. The benefit of such an MEA is to offer a unique noninvasive method to study single cells without destroying them with the time-consuming patch clamp method, and without losing cell-specific information, which often occurs if the cell clusters studied with standard MEAs are too heterogenous. This was achieved with a number of innovations. For example, the electrodes were placed near the perimeter of the cell culturing area and had a larger diameter (80 μm) than the usual 30 μm electrodes. This simplified the plating of the cells to the electrodes and enabled the beating of the cells to be electrically recorded. It is also possible to combine that with image-based analysis of mechanical beating through transparent indium tin oxide (ITO) electrodes

Novel flexible multielectrode arrays for neuronal stimulation and recording

This thesis will focus on developments in coupling the multidisciplinary research interests of Physics, Micro-engineering and neurobiology towards the development of a proof of concept retinal prosthetic device. With recent developments in low-power electronics and semiconductor fabrication techniques many applications in the life sciences have emerged. One such application is in the development of a retinal prosthetic device which relies on the ability to record information from and feed information directly to small retinal neuronal cells which are approximately 5mum diameter. Where successful, we achieve the possibility of restoring sight to people affected by degenerative visual diseases such as Age Related Macular Degeneration and Retinitis Pigmentosa. Both these conditions affect the photosensitive elements of the eye yet leave the remaining pathways to the visual cortex, the area of the brain responsible for our visual precept, intact. High-density electrode arrays axe becoming well established as tools for the measurement of neuronal signals. The fabrication of arrays on flexible materials allows for 2D position sensitive recording of cellular activity in vivo and for the possibility of direct in vivo stimulus. Using flexible polymer materials (Pryalin PI2545), compliant with semiconductor fabrication techniques, a process allowing the fabrication of flexible multi-site microelectrode neuronal recording and stimulating arrays is presented. The development of both 8 and 74 electrode arrays on polyimide substrates with 50mum and 5mum minimum linewidths respectively is described. Implementing low noise amplification, 8muV rms (bandpass typically 80-2000 Hz), the polyimide 8-electrode arrays have been used to stimulate and record electroretinogram and ganglion cell action potentials in vivo from the frog retina (Rana lemporaria). Such arrays coupled to our application specific pixellated CMOS sensors, the IPIX, incorporating an ability to apply neural network algorithms should allow for the recovery of basic functionality in the human retina. The IPIX detector is an Active Pixel Sensor which responds to incident light in the visible region. It responds to the varying intensity of light over 3 log units and outputs varying frequency voltage pulses of similar form to that of a healthy retina. Stimulation studies for electro-deposited platinum electrodes of 4 nA/mum2 indicate upper breakdown limits for charge density approaching 100 muCm-2. Investigations of lifetime stimulation of a 50 mum diameter electrode, of typical impedance less than 20 kO at 1 kHz, suggest operational limits over lifetime in the order of 10 muCm-2. These charge densities are adequate for neuronal cell stimulation. It is believed that the system described in this thesis can form the basis on which to deploy a retinal prosthetic device. Moreover, in the short term, the information provided by this system will allow for investigations into deciphering the 'wiring diagram' of the retina

Piezoelectric microsensors for semiochemical communication

Chemical communication plays vital role in the mediating the behaviour of an organism living in the “odour space”. The mechanisms by which odours are generated and detected by the organism has evolved over thousands of years and thus the potential advantages of translating this system into a fully functional communication system has opened new avenues in the area of multi-disciplinary research. This formed the basis of the Biosynthetic Infochemical Communications project – iCHEM whose central aim was to develop a new class of communication technology based on the biosynthesis pathways of the moth, S. littoralis. This novel infochemical communication system would consist of a “chemoemitter” unit which would generate a precise mix of infochemicals which after travelling through the odour space would be detected by a complementary tuned detector – the “chemoreceiver” unit comprising of a ligand specific detection element and an associated biophysical model functioning similar to the antennal lobe neuron of the moth. This combined novel system will have the capability of communicating by the help of chemicals only, in the vapour or liquid phase. For the work presented in this thesis, the novel concept of infochemical communication has been examined in the vapour and liquid phase by employing piezoelectric microsensors. This has been achieved and demonstrated throughout the thesis by employing chemo-specific acoustic wave microsensors. For vapour phase assessment, quartz crystal microbalance, were coated with different organic polymer coatings and incorporated in a prototype infochemical communication system detecting encoded volatiles. For liquid phase assessment, shear horizontal surface acoustic wave (SH-SAW) microsensors were specifically designed and immobilised within Sf9 insect cells. This GPCR based whole cell biosensing system was then employed to detect ligand specific activations thus acting as a precursor to the development of a fully functionalised OR based signalling system, thus contributing to the growing field of communication and labelling technology