Modulating Electrode Kinetics for Discrimination of Dopamine by a PEDOT:COOH Interface Doped with Negatively Charged Tricarboxylate

The rapidly developing field of conducting polymers in organic electronics has many implications for bioelectronics. For biosensing applications, tailoring the functionalities of the conducting polymer’s surface is an efficient approach to improve both sensitivity and selectivity. Here, we demonstrated a facile and economic approach for the fabrication of a high-density, negatively charged carboxylic-acid-group-functionalized PEDOT (PEDOT:COOH) using an inexpensive ternary carboxylic acid, citrate, as a dopant. The polymerization efficiency was significantly improved by the addition of LiClO4 as a supporting electrolyte yielding a dense PEDOT:COOH sensing interface. The resulting PEDOT:COOH interface had a high surface density of carboxylic acid groups of 0.129 μmol/cm2 as quantified by the toluidine blue O (TBO) staining technique. The dopamine response measured with the PEDOT:COOH sensing interface was characterized by cyclic voltammetry with a significantly reduced ΔEp of 90 mV and a 3-fold increase in the Ipa value compared with those of the nonfunctionalized PEDOT sensing interface. Moreover, the cyclic voltammetry and electrochemical impedance spectroscopy results demonstrated the increased electrode kinetics and highly selective discrimination of dopamine (DA) in the presence of the interferents ascorbic acid (AA) and uric acid (UA), which resulted from the introduction of negatively charged carboxylic acid groups. The negatively charged carboxylic acid groups could favor the transfer, preconcentration, and permeation of positively charged DA to deliver improved sensing performance while repelling the negatively charged AA and UA interferents. The PEDOT:COOH interface facilitated measurement of dopamine over the range of 1–85 μM, with a sensitivity of 0.228 μA μM–1, which is 4.1 times higher than that of a nonfunctionalized PEDOT electrode (0.055 μA μM–1). Our results demonstrate the feasibility of a simple and economic fabrication of a high-density PEDOT:COOH interface for chemical sensing, which also has the potential for coupling with other biorecognition molecules via carboxylic acid moieties for the development of a range of advanced PEDOT-based biosensor

Conducting polymer-reinforced laser-irradiated graphene as a heterostructured 3D transducer for flexible skin patch biosensors

Flexible skin patch biosensors are promising for the noninvasive determination of physiological parameters in perspiration for fitness and health monitoring. However, various prerequisites need to be met for the development of such biosensors, including the creation of a flexible conductive platform, bending/contact stability, fast electrochemical kinetics, and immobilization of biomolecules. Here, we describe a conducting polymer-reinforced laser-irradiated graphene (LIG) network as a heterostructured three-dimensional (3D) transducer for flexible skin patch biosensors. LIG with a hierarchically interconnected graphene structure is geometrically patterned on polyimide via localized laser irradiation as a flexible conductive platform, which is then reinforced by poly(3,4-ethylenedioxythiophene) (PEDOT) as a conductive binder (PEDOT/LIG) with improved structural/contact stability and electrochemical kinetics. The interconnected pores of the reinforced PEDOT/LIG function as a 3D host matrix for high loading of “artificial” (Prussian blue, PB) and natural enzymes (lactate oxidase, LOx), forming a compact and heterostructured 3D transducer (LOx/PB-PEDOT/LIG) for lactate biosensing with excellent sensitivity (11.83 μA mM–1). We demonstrated the fabrication of flexible skin patch biosensors comprising a custom-built integrated three-electrode system achieve amperometric detection of lactate in artificial sweat over a wide physiological linear range of 0–18 mM. The advantage of this facile and versatile transducer is further illustrated by the development of a folded 3D wristband lactate biosensor and a dual channel biosensors for simultaneous monitoring of lactate and glucose. This innovative design concept of a heterostructured transducer for flexible biosensors combined with a versatile fabrication approach could potentially drive the development of new wearable and skin-mountable biosensors for monitoring various physiological parameters in biofluids for noninvasive fitness and health management

Soft and flexible material-based affinity sensors

Recent advances in biosensors and point-of-care (PoC) devices are poised to change and expand the delivery of diagnostics from conventional lateral-flow assays and test strips that dominate the market currently, to newly emerging wearable and implantable devices that can provide continuous monitoring. Soft and flexible materials are playing a key role in propelling these trends towards real-time and remote health monitoring. Affinity biosensors have the capability to provide for diagnosis and monitoring of cancerous, cardiovascular, infectious and genetic diseases by the detection of biomarkers using affinity interactions. This review tracks the evolution of affinity sensors from conventional lateral-flow test strips to wearable/implantable devices enabled by soft and flexible materials. Initially, we highlight conventional affinity sensors exploiting membrane and paper materials which have been so successfully applied in point-of-care tests, such as lateral-flow immunoassay strips and emerging microfluidic paper-based devices. We then turn our attention to the multifarious polymer designs that provide both the base materials for sensor designs, such as PDMS, and more advanced functionalised materials that are capable of both recognition and transduction, such as conducting and molecularly imprinted polymers. The subsequent content discusses wearable soft and flexible material-based affinity sensors, classified as flexible and skin-mountable, textile materials-based and contact lens-based affinity sensors. In the final sections, we explore the possibilities for implantable/injectable soft and flexible material-based affinity sensors, including hydrogels, microencapsulated sensors and optical fibers. This area is truly a work in progress and we trust that this review will help pull together the many technological streams that are contributing to the field

Tunable 3D nanofibrous and bio-functionalised PEDOT network explored as a conducting polymer-based biosensor

Conducting polymers that possess good electrochemical properties, nanostructured morphology and functionality for bioconjugation are essential to realise the concept of all-polymer-based biosensors that do not depend on traditional nanocatalysts such as carbon materials, metal, metal oxides or dyes. In this research, we demonstrated a facile approach for the simultaneous preparation of a bi-functional PEDOT interface with a tunable 3D nanofibrous network and carboxylic acid groups (i.e. Nano-PEDOT-COOH) via controlled co-polymerisation of EDOT and EDOT-COOH monomers, using tetrabutylammonium perchlorate as a soft-template. By tuning the ratio between EDOT and EDOT-COOH monomer, the nanofibrous structure and carboxylic acid functionalisation of Nano-PEDOT-COOH were varied over a fibre diameter range of 15.6 ± 3.7 to 70.0 ± 9.5 nm and a carboxylic acid group density from 0.03 to 0.18 μmol cm−2. The nanofibres assembled into a three-dimensional network with a high specific surface area, which contributed to low charge transfer resistance and high transduction activity towards the co-enzyme NADH, delivering a wide linear range of 20–960 μM and a high sensitivity of 0.224 μA μM−1 cm−2 at the Nano-PEDOT-COOH50% interface. Furthermore, the carboxylic acid groups provide an anchoring site for the stable immobilisation of an NADH-dependent dehydrogenase (i.e. lactate dehydrogenase), via EDC/S–NHS chemistry, for the fabrication of a Bio-Nano-PEDOT-based biosensor for lactate detection which had a response time of less than 10 s over the range of 0.05–1.8 mM. Our developed bio-Nano-PEDOT interface shows future potential for coupling with multi-biorecognition molecules via carboxylic acid groups for the development of a range of advanced all-polymer biosensor

Bi-functional sulphonate-coupled reduced graphene oxide as an efficient dopant for a conducting polymer with enhanced electrochemical performance

The rapidly emerging field of organic bioelectronics has witnessed the wide use of conducting polymers (CPs) to fabricate advanced chemically modified electrodes (CMEs) for biosensors and biomedical devices. The electrochemical performance of the CPs in such devices is closely related to the quality and physiochemical nature of the dopants. A bi-functional graphene oxide derivative with high reduction degree and negatively-charged sulphonate functionality, i.e. sulphonate-coupled reduced graphene oxide (S-RGO), was developed and used as an efficient dopant for a CP with enhanced electrochemical performance. The S-RGO was synthesised via a facile one-pot hydrothermal reaction using 4-hydrazinobenzosulphonic acid (4-HBS) as reductant and sulphonate precursor simultaneously. The resulting S-RGO possesses high aqueous dispersion stability (more than 6 months), high electrical conductivity (1493.0 S m−1) and sulphonate functionality. Due to these specific properties, S-RGO demonstrated improved electropolymerisation efficiency for poly(3,4-ethylenedioxythiophene) (PEDOT) proving an effective dopant for the preparation of a PEDOT:S-RGO film (5 mC) with faster polymerisation time (37 s) compared to the conventional 2D dopants GO (PEDOT:GO, 129 s) and RGO (PEDOT:RGO, 66 s). The resulting PEDOT:S-RGO appeared as a homogenous film with uniformly distributed S-RGO dopant, low equivalent series resistance and low charge transfer resistance. Moreover, the electrochemical transduction performance of the PEDOT:S-RGO interface was evaluated with 4 different analytes, including ferric/ferrocyanide redox probe, dopamine, nicotinamide adenine dinucleotide and hydrogen peroxide. As a result of the synergistic effect of S-RGO and PEDOT, the PEDOT:S-RGO demonstrated enhanced electrochemical performance with respect to faster electrode kinetics (smaller ΔEp), ∼2 and ∼4 times increased current responses, and lower peak potentials compared to PEDOT:GO and PEDOT:RGO. This bi-functional S-RGO dopant combined the advantages of conventional GO and RGO to deliver sulphonate functionality and high conductivity for the preparation of advanced PEDOT interface with improved electrochemical performance, that could potentially be applied for applications in electrochemical sensors, biosensors and bioelectronic device

Processable and nanofibrous polyaniline:polystyrene-sulphonate (nano-PANI:PSS) for the fabrication of catalyst-free ammonium sensors and enzyme-coupled urea biosensors

Tailoring conducting polymers (CPs) such as polyaniline (PANI) to deliver the appropriate morphology, electrochemical properties and processability is essential for the development of effective polymer-based electrochemical sensors and biosensors. Composite PANI electrodes for the detection of ammonium (NH4+) have been previously reported, but have been limited by their reliance on the electrocatalytic reaction between NH4+ and a metal/nano-catalyst. We report an advanced processable and nanofibrous polyaniline:polystyrene-sulphonate (nano-PANI:PSS) as a functional ink for the fabrication of catalyst-free NH4+ sensors and enzyme-coupled urea biosensors. The PSS provides both a soft-template for nanofibre formation and a poly-anionic charge compensator, enabling the detection of NH4+ based on an intrinsic doping/de-doping mechanism. The nanostructured morphology, chemical characteristics and electrochemical properties of the nano-PANI:PSS were characterised. We fabricated 3D-hierarchical sensor interfaces composed of inter-connected nano-PANI:PSS fibres (diameter of ~50.3 ± 4.8 nm) for the detection of NH4+ with a wide linear range of 0.1–11.5 mM (R2 = 0.996) and high sensitivity of 106 mA M−1 cm−2. We further demonstrated the coupling of the enzyme urease with the nano-PANI:PSS to create a urea biosensor with an innovative biocatalytic product-to-dopant relay mechanism for the detection of urea, with a linear range of 0.2–0.9 mM (R2 = 0.971) and high sensitivity of 41 mA M−1 cm−2. Moreover, the nano-PANI:PSS-based sensors show good selectivity for the detection of NH4+and urea in a urine model containing common interfering molecules. This processable and fibrous nano-PANI:PSS provides new advance on CP-based transducer materials in the emerging field of printed organic sensors and biosensors

Search for light dark matter from atmosphere in PandaX-4T

We report a search for light dark matter produced through the cascading decay of $\eta$ mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasi-elastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne$\cdot$year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross-section is set at $5.9 \times 10^{-37}{\rm cm^2}$ for dark matter mass of $0.1$ MeV$/c^2$ and mediator mass of 300 MeV$/c^2$. The lowest upper limit of $\eta$ to dark matter decay branching ratio is $1.6 \times 10^{-7}$

A Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T

We report a search on a sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne-year exposure collected by PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and electrons. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such dark matter into photon final states. In particular, we present the first direct detection limits for an axial-vector (vector) interaction which are the strongest in the mass range from 25 to 45 (35 to 50) keV/c$^2$

Tailoring Conducting Polymer Interface for Sensing and Biosensing

The routine measurement of significant physiological and biochemical parameters has become increasingly important for health monitoring especially in the cases of elderly people, infants, patients with chronic diseases, athletes and soldiers etc. Monitoring is used to assess both physical fitness level and for disease diagnosis and treatment. Considerable attention has been paid to electrochemical sensors and biosensors as point-of-care diagnostic devices for healthcare management because of their fast response, low-cost, high specificity and ease of operation. The analytical performance of such devices is significantly driven by the high-quality sensing interface, involving signal transduction at the transducer interface and efficient coupling of biomolecules at the transducer bio-interface for specific analyte recognition. The discovery of functional and structured materials, such as metallic and carbon nanomaterials (e.g. gold and graphene), has facilitated the construction of high-performance transducer interfaces which benefit from their unique physicochemical properties. Further exploration of advanced materials remains highly attractive to achieve well-designed and tailored interfaces for electrochemical sensing and biosensing driven by the emerging needs and demands of the “Internet of Things” and wearable sensors. Conducting polymers (CPs) are emerging functional polymers with extraordinary redox reversibility, electronic/ionic conductivity and mechanical properties, and show considerable potential as a transducer material in sensing and biosensing. While the intrinsic electrocatalytic property of the CPs is limited, especially for the bulk polymer, tailoring of CPs with controlled structure and efficient dopants could improve the electrochemical performance of a transducer interface by delivering a larger surface area and enhanced electrocatalytic property. In addition, the rich synthetic chemistry of CPs endows them with versatile functional groups to modulate the interfacial properties of the polymer for effective biomolecule coupling, thus bridging organic electronics and bioelectrochemistry. Moreover, the soft-material characteristics of CPs enable their use for the development of flexible and wearable sensing platforms which are inexpensive and light-weight, compared to conventional rigid materials, such as carbons, metals and semiconductors. This thesis focuses on the exploration of CPs for electrochemical sensing and biosensing with improved sensitivity, selectivity and stability by tailoring CP interfaces at different levels, including the CP-based transduction interface, CP-based bio-interface and CP-based device interface. First, we demonstrate different strategies for tailoring the physicochemical properties of poly (3,4-ethylenedioxythiophene) (PEDOT) beyond its intrinsic properties, via charge effects, structural effects and by the use of hybrid materials, as a CP-based transduction interface to improve sensing performance of various analytes. 1) A positively-charged PEDOT interface, and a negatively-charged carboxylic-acid-functionalised PEDOT (PEDOT:COOH) interface were developed to modulate the electrode kinetics for oppositely-charged analytes, e.g. negatively-charged nicotinamide adenine dinucleotide (NADH) and positively-charged dopamine (DA), respectively. These interfaces displayed high sensitivity and wide linear range towards the analytes due to the electrostatic attraction effect. 2) Various structured PEDOT including porous microspheres and nanofibres were synthesised via hard-template and soft-template methods, respectively, and were employed as building blocks for a hierarchical PEDOT and 3D nanofibrous PEDOT transduction interface, that facilitated signal transduction for NADH. 3) A PEDOT hybrid material interface was developed via using a novel bi-functional graphene oxide derivative with high reduction degree and negatively-charged sulphonate terminal functionality (S-RGO) as dopant to create PEDOT:S-RGO which delivered an enhanced electrochemical performance for various analytes. Based on the established CP-based transduction interface, biomolecules (e.g. enzymes) could be coupled to the CP surface to create CP-based bio-interfaces for biosensing. The immobilisation of enzyme was realised via either covalent bonding to a PEDOT derivative bearing a -COOH group (PEDOT-COOH) through EDC/NHS chemistry, or by physical absorption into the 3D porous PEDOT structure. The CP-based bio-interfaces were used to demonstrate the stable immobilisation of two different types of enzymes, i.e. lactate dehydrogenase and lactate oxidase, achieving the biosensing of analytes by relay bioelectrochemical signal transduction. Together, CP was employed as the CP-based device interface for the fabrication of a flexible and wearable biosensing device. A 3D honeycomb-structured graphene network was generated in-situ on a flexible polyimide surface by mask-free patterning using laser irradiation. The substrate was then reinforced with PEDOT as a polymeric binder to stabilise the 3D porous network by adhesion and binding, thus minimising the delamination of the biosensing interface under deformation and enhancing the mechanical behaviours for use in flexible and wearable devices. The subsequent nanoscale-coating of Prussian blue and immobilisation of enzyme into the 3D porous network provided a flexible platform for wearable electrochemical biosensors to detect lactate in sweat.Rutinmässig övervakning av hälsorelaterade fysiologiska och biokemiska parametrar har blivit allt viktigare för ett stort antal människor bland annat seniorer, spädbarn, patienter med kroniska sjukdomar, idrottare, soldater och med flera, på både en fysisk nivå för förebyggande av sjukdomar samt på en medicinsk nivå för diagnos och behandling av sjukdomar. Stor uppmärksamhet har lagts på utveckling av elektrokemiska sensorer och biosensorer som point-of-care (PoC) diagnostiska enheter for rutinmässig sjukvårdsledning genom deras snabba svar, låga kostnad, höga specificitet och enkla drift. Deras analytiska funktioner drivs av avkänningsgranssnittet vilket involverar signaltransduktion vid transducer-gränssnittet och effektiv koppling av biomolekyler till transducer-biogränssnittet för specifik analytigenkänning. Upptäckten av konventionella funktionella och strukturerade material, t.ex. metalliska nanopartiklar, kolnanorör och grafen, har underlättat konstruktionen av transducergränssnitt med hög prestanda på grund av deras unika fysiokemiska egenskaper. Ytterligare forskning av avancerade material ar önskvärt for att uppnå ett väldesignat och skräddarsytt gränsnitt for elektrokemisk avkänning och biosensering for Internet of Things och klädd sensorer. Ledande polymerer (LP) ar en typ av nya funktionella polymerer med extraordinär redoxomvändbarhet, elektronisk/jonisk ledningsförmåga och mekaniska egenskaper, som uppvisar betydande potential som ett givarmaterial vid avkänning och biosensering. Medan de inneboende elektrokatalytiska egenskaperna i LP:er är begränsade, speciellt for den skrymmande polymeren, kan skräddarsydda LP:er med kontrollerad struktur och effektiva dopmedel förbättra den elektrokemiska prestandan hos ett givargränssnitt med större ytarea och förbättrade elektrokatalytiska egenskaper. Dessutom ger den syntetiska kemin LP:er mångsidiga funktionella grupper för att modulera gränssnittsegenskaperna för LP:er för att förbättra selektivitet for analytdetektering, såväl som för effektiv biomolekylkoppling som ett biogränssnitt som överbryggar den organiska elektroniken och det biologiska system som stöds av de LP:s organkemiska natur. Dessutom möjliggör de mjuka materialegenskaperna för LP:er för användning i utveckling av en flexibla och bärbara avkänningsplattformar med låg kostnad och lätt vikt, jämfört med konventionella styva material, såsom metaller och halvledare. Denna avhandling fokuserar på utforskning av LP:er för elektrokemisk avkänning och biosensering med förbättrad känslighet, selektivitet och stabilitet genom att skräddarsy LP:s gränssnitt i olika nivåer, inklusive LP-baserat transduktionsgränssnitt, LP-baserat bio-gränssnitt och LP-baserat enhetsgränssnitt. Först demonstrerar vi olika strategier for att skräddarsy fysikalisk-kemiska egenskaper hos poly (3,4-etylendioxytiofen) (PEDOT) som ett LP-baserat transduktionsgränssnitt för avkänning via laddningseffekter, struktureffekter och hybridmaterialeffekter för förbättrad prestanda för olika analyser utöver dess inre egenskaper. 1) Ett positivt laddat hierarkiskt PEDOT-gränssnitt och ett negativt laddat karboxylsyra-funktionaliserad PEDOT (PEDOT: COOH) gränssnitt utvecklades for att modulera gränssnittets kinetik for de motsatt laddade analyterna, t.ex. negativt laddad s-Nicotinamidadeninudukleotid (NADH) respektive positivt laddat dopamin (DA). Den elektrokemiska avkänningsprestandan hos dessa analyser förbättrades baserat på laddningseffekten med högre känslighet och ett bredare linjärt intervall. 2) Med tanke på den väl skrymmande filmbildande egenskapen och den resulterande låga tillgängliga aktiva ytan för PEDOT, syntetiserades olika strukturerade PEDOT inklusive porösa mikrosfärer och nanofibrer via en hård mall respektive en mjuk mall och användes sedan som byggstenar för hierarkiska PEDOT och 3D nanofibrosa PEDOT-transduktionsgränssnitt, vilket underlättar signaltransduktion for NADH. 3) Ett LP-hybridmaterialgränssnitt utvecklades med användning av ett nytt bi-funktionellt grafenoxidderivat med hög reduktionsgrad och negativt laddad sulfonatterminal funktionalitet (S-RGO) med förbättrad elektrokemisk prestanda fär olika analyser. Baserat på det etablerade LP-baserade transduktionsgränssnittet utvecklades sedan de LP-baserade bio-gränssnitten med immobilisering av biomolekyler (t.ex. enzym) för biosensering. Immobiliseringen av enzym på LP-gränssnittet realiserades via antingen kovalent bindning till PEDOT-derivatbärande -COOH-grupper (PEDOT-COOH) genom EDC/NHS-kemi eller fysisk absorption i porösa 3D-PEDOT-strukturer. De LP-biobaserade gränssnitten visar stabil immobilisering av två olika typer av enzymer, d.v.s. laktatdehydrogenas och laktatoxidas, vilket uppnår biosensering av analyter genom en successiv bioelektrokemisk signaltransduktion. Tillsammans användes LP:er som det LP-baserade enhetsgränssnittet för tillverkning av en flexibel och bärbar biosenseringsanordning. Ett tredimensionellt bikakestrukturerat grafennatverk genererades in-situ på den flexibla polyimidytan genom maskfri mönstring med laserbestrålningsteknik. Substratet förstärktes sedan med nanodeponerat PEDOT som ett polymert bindemedel for att stabilisera det porösa 3D-nätverket genom vidhäftning och bindning, vilket sålunda förbättrade det mekaniska beteendet för flexibla och bärbara anordningar. Den sekventiella beläggningen på nanoskala av Preussiskt blått (PB) och immobiliseringen av enzym i det porösa 3Dnatverket minimerade delaminering av biosenseringsgränssnittet vid deformation, vilket försedde en flexibel plattform för en bärbar elektrokemisk biosensor för detektering av laktat i svett med det monterade treelektrodsystemet