Infections occurring in the mother and neonate exert a substantial health burden worldwide. Optimising infection management is crucial for improving individual outcomes and reducing the incidence of antimicrobial resistance. Digital health technologies, through their accessibility and scalability, hold promise in improving the quality of care across diverse health-care settings. In settings with poor access to laboratory services, innovative uses of existing data, point-of-care diagnostics, and wearables could allow for better recognition of host responses during infection and antimicrobial optimisation. The linkage and connectivity of information can support the coordinated delivery of care between health-care facilities and the community. Continuous real-time monitoring of infection markers in the mother and neonate through biosensing can provide notable opportunities for intervention and improvements in care. However, the development and implementation of these interventions should be respectful, prioritise safety, and emphasise sustainable, locally derived solutions. Addressing existing gender, economic, and health-care disparities will be essential for ensuring equitable implementation.

Microneedle lactate sensors may be used to continuously measure lactate concentration in the interstitial fluid in a minimally invasive and pain-free manner. First- and second-generation enzymatic sensors produce a redox-active product that is electrochemically sensed at the electrode surface. Direct electron transfer enzymes produce electrons directly as the product of enzymatic action; in this study, a direct electron transfer enzyme specific to lactate has been immobilized onto a microneedle surface to create lactate-sensing devices that function at low applied voltages (0.2 V). These devices have been validated in a small study of human volunteers; lactate concentrations were raised and lowered through physical exercise and subsequent rest. Lactazyme microneedle devices show good agreement with concurrently obtained and analyzed serum lactate levels.

IntroductionDetermination of blood lactate levels supports decision-making in a range of medical conditions. Invasive blood-sampling and laboratory access are often required, and measurements provide a static profile at each instance. We conducted a phase I clinical study validating performance of a microneedle patch for minimally invasive, continuous lactate measurement in healthy volunteers.MethodsFive healthy adult participants wore a solid microneedle biosensor patch on their forearms and undertook aerobic exercise for 30 min. The microneedle biosensor quantifies lactate concentrations in interstitial fluid within the dermis continuously and in real-time. Outputs were captured as sensor current and compared with lactate concentrations from venous blood and microdialysis.ResultsThe biosensor was well-tolerated. Participants generated a median peak venous lactate of 9.25 mmol/L (IQR 6.73–10.71). Microdialysate concentrations of lactate closely correlated with blood. Microneedle biosensor current followed venous lactate concentrations and dynamics, with good agreement seen in all participants. There was an estimated lag-time of 5 min (IQR −4 to 11 min) between microneedle and blood lactate measurements.ConclusionThis study provides first-in-human data on use of a minimally invasive microneedle patch for continuous lactate measurement, providing dynamic monitoring. This low-cost platform offers distinct advantages to frequent blood sampling in a wide range of clinical settings, especially where access to laboratory services is limited or blood sampling is infeasible. Implementation of this technology in healthcare settings could support personalised decision-making in a variety of hospital and community settings.Trial registration numberNCT04238611.

Recent advances in the field of microneedle devices are having an impact on both diagnostic and therapeutic approaches to sustaining healthy populations globally. Whether this is for improving drug and vaccine efficacy or for continuous sensing of key molecular indicators, the past five years have seen increased activity in both the academic and commercial sectors. In this Perspective, we focus on solid microneedle biosensors and discuss the advantages of these devices over alternative clinical diagnostic platforms as well as the technical challenges presented. We will emphasize how their use in continuous measurement of molecules in vivo is made possible with a minimally invasive technique that is simple to perform. This Perspective describes the function and current state of microneedle sensor arrays for the in vivo measurement of both endogenous molecules such as glucose and lactate and drugs such as penicillin.

Antimicrobial resistance poses a global threat to patient health. Improving the use and effectiveness of antimicrobials is critical in addressing this issue. This includes optimizing the dose of antibiotic delivered to each individual. New sensing approaches that track antimicrobial concentration for each patient in real time could allow individualized drug dosing. This work presents a potentiometric microneedle-based biosensor to detect levels of β-lactam antibiotics in vivo in a healthy human volunteer. The biosensor is coated with a pH-sensitive iridium oxide layer, which detects changes in local pH as a result of β-lactam hydrolysis by β-lactamase immobilized on the electrode surface. Development and optimization of the biosensor coatings are presented, giving a limit of detection of 6.8 μM in 10 mM PBS solution. Biosensors were found to be stable for up to 2 weeks at -20 °C and to withstand sterilization. Sensitivity was retained after application for 6 h in vivo. Proof-of-concept results are presented showing that penicillin concentrations measured using the microneedle-based biosensor track those measured using both discrete blood and microdialysis sampling in vivo. These preliminary results show the potential of this microneedle-based biosensor to provide a minimally invasive means to measure real-time β-lactam concentrations in vivo, representing an important first step toward a closed-loop therapeutic drug monitoring system.

Background Enhanced methods of drug monitoring are required to support the individualisation of antibiotic dosing. We report the first-in-human evaluation of real-time phenoxymethylpenicillin monitoring using a minimally invasive microneedle-based beta-lactam biosensor in healthy volunteers. Methods This first-in-human, proof-of-concept study was done at the National Institute of Health Research/Wellcome Trust Imperial Clinical Research Facility (Imperial College London, London, UK). The study was approved by London-Harrow Regional Ethics Committee. Volunteers were identified through emails sent to a healthy volunteer database from the Imperial College Clinical Research Facility. Volunteers, who had to be older than 18 years, were excluded if they had evidence of active infection, allergies to penicillin, were at high risk of skin infection, or presented with anaemia during screening. Participants wore a solid microneedle beta-lactam biosensor for up to 6 h while being dosed at steady state with oral phenoxymethylpenicillin (five 500 mg doses every 6 h). On arrival at the study centre, two microneedle sensors were applied to the participant's forearm. Blood samples (via cannula, at -30, 0, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 min) and extracellular fluid (ECF; via microdialysis, every 15 min) pharmacokinetic (PK) samples were taken during one dosing interval. Phenoxymethylpenicillin concentration data obtained from the microneedles were calibrated using locally estimated scatter plot smoothing and compared with free-blood and microdialysis (gold standard) data. Phenoxymethylpenicillin PK for each method was evaluated using non-compartmental analysis. Area under the concentration-time curve (AUC), maximum concentration, and time to maximum concentration were compared. Bias and limits of agreement were investigated with Bland-Altman plots. Microneedle biosensor limits of detection were estimated. The study was registered with ClinicalTrials.gov, number NCT03847610. Findings Ten healthy volunteers participated in the study. Mean age was 42 years (SD 14). Seven (70%) were men. Microdialysis and microneedle results were similar for phenoxymethylpenicillin ECF maximum concentration (0.74 mg/L vs 0.64 mg/L; 95% CI -0.24 to 0.44; p=0.53), time to maximum concentration (1.18 h vs 1.10 h; -0.52 to 0.67; p=0.79), and AUC (1.54 mg x h/L vs 1.67 mg x h/L; -1.10 to 0.85; p=0.79). In total, 440 time points were compared with mean difference between measurements -0.16 mg/L (95% CI -1.30 to 0.82). Mean phenoxymethylpenicillin AUCs for free serum and microneedle PK were similar (1.77 mg x h/L [SD 0.59] vs 1.67 mg x h/L [1.00]; -0.77 to 0.97; p=0.81). Median coefficient of variation between sensors within individuals was 7% (IQR 4-17). Limit of detection for the microneedles was estimated at 0.17 mg/L. Interpretation This study is proof-of-concept of real-time, microneedle sensing of penicillin in vivo. Future work will explore microneedle use in patient populations, their role in data generation to inform dosing recommendations, and their incorporation into closed-loop control systems for automated drug delivery. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.

A paucity of data describing citizen perceptions of novel technologies, including those containing unsupervised computer-controlled systems is currently available. We explored citizen perceptions of using a microneedle biosensor and automated dose control system at a university public festival. Groups of citizens (from 2-6 people per group) attended a short demonstration of a microneedle biosensor and automated dosing system versus a traditional phlebotomy approach over a two-day public festival. Individual groups discussed and reached consensus on a number of short questions regarding their perceptions on the acceptability of such technology. Over the two days, 100 groups participated (56/100 day 1 and 44/100 day 2). The majority of individuals reported high acceptability of microneedle technology (median Likert score 9/10), but the majority believed that doctors should decide what dose of antibiotic is delivered (75/100; 75%). Groups concurred with the acceptability of microneedles to reduce blood tests and pain associated with them. However, concerns were reported over unsupervised computer-controlled programmes making decision about antibiotic dosing. This was driven by concerns over computer error and the inability of systems to contextualise decision making to the human and social context. Future work must consider the greater role of citizen engagement in the development of such technologies, to ensure their acceptability upon implementation in clinical practice.

Triplet states are ubiquitous in organic electronics and their properties are increasingly being exploited to enhance device efficiencies. The difficulty in accurately probing triplet states dictates that more fundamental understanding is required of their properties. In this work, a hybrid co-polymer of poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8BT) with 10% by weight zinc porphyrin was synthesized and a transient absorption spectroscopy study performed. It was observed that a dual energy-transfer mechanism was active, whereby the ultimate fate of each photogenerated F8BT singlet exciton depended upon its distance to a porphyrin unit. F8BT excitons generated within the bulk of the F8BT polymer showed typical F8BT photophysics, with the small proportion of F8BT triplets created able to diffuse to and undergo triplet energy transfer to the porphyrin units. In contrast, F8BT singlet excitons formed within their diffusion length to a porphyrin unit displayed singlet energy transfer, followed by intersystem crossing to create the lower energy porphyrin triplet. Intriguingly, the F8BT-HAPAPP triplets generated have a lifetime intermediate between the two pristine materials. Density functional theory calculations suggest that this is due to orbital mixing between energetically close benzothiadiazole and porphyrin-localized molecular orbitals, creating a mixed F8BT/porphyrin triplet state.

The presence of energetically low-lying triplet states is a hallmark of organic semiconductors. Even though they present a wealth of interesting photophysical properties, these optically dark states significantly limit optoelectronic device performance. Recent advances in emissive charge-transfer molecules have pioneered routes to reduce the energy gap between triplets and "bright" singlets, allowing thermal population exchange between them and eliminating a significant loss channel in devices. In conjugated polymers, this gap has proved resistant to modification. Here, we introduce a general approach to reduce the singlet-triplet energy gap in fully conjugated polymers, using a donor-orthogonal acceptor motif to spatially separate electron and hole wave functions. This new generation of conjugated polymers allows for a greatly reduced exchange energy, enhancing triplet formation and enabling thermally activated delayed fluorescence. We find that the mechanisms of both processes are driven by excited-state mixing between π-π*and charge-transfer states, affording new insight into reverse intersystem crossing.

A novel solid-state design is presented for an organic intermediate band solar cell with electrically integrated triplet–triplet annihilation upconversion.

Herein, this study investigates the impact of branching‐point‐extended alkyl chains on the charge transport properties of three ultrahigh n‐type mobility conjugated polymers. Using grazing incidence wide‐angle X‐ray scattering, analysis of the crystallinity of the series shows that while π–π interactions are increased for all three polymers as expected, the impact of the side‐chain engineering on polymer backbone crystallinity is unique to each polymer and correlates to the observed changes in charge transport. With the three polymers exhibiting n‐type mobilities between 0.63 and 1.04 cm 2 V −1 s −1 , these results ratify that the indolonaphthyridine building block has an unprecedented intrinsic ability to furnish high‐performance n‐type organic semiconductors.

Herein, we present the synthesis and characterization of four conjugated polymers containing a novel chromophore for organic electronics based on an indigoid structure. These polymers exhibit extremely small band gaps of ∼1.2 eV, impressive crystallinity, and extremely high n-type mobility exceeding 3 cm2 V s–1. The n-type charge carrier mobility can be correlated with the remarkably high crystallinity along the polymer backbone having a correlation length in excess of 20 nm. Theoretical analysis reveals that the novel polymers have highly rigid nonplanar geometries demonstrating that backbone planarity is not a prerequisite for either narrow band gap materials or ultrahigh mobilities. Furthermore, the variation in backbone crystallinity is dependent on the choice of comonomer. OPV device efficiencies up to 4.1% and charge photogeneration up to 1000 nm are demonstrated, highlighting the potential of this novel chromophore class in high-performance organic electronics.

A novel, highly soluble chromophore for use in organic electronics based on an indigoid structure is reported. Copolymerization with thiophene affords an extremely narrow band gap polymer with a maximum absorption at similar to 800 nm. The novel polymer exhibits high crystallinity and high ambipolar transport in OFET devices of 0.23 cm(2) V-1 s(-1) for holes and 0.48 cm(2) V-1 s(-1) for electrons. OPV device efficiencies up to 2.35% with light absorbance up to 950 nm demonstrate the potential for this novel chromophore in near-IR photovoltaics.

We present the synthesis of a novel diphenylanthracene (DPA) based semiconducting polymer. The polymer is solubilised by alkoxy groups attached directly to a DPA monomer, meaning the choice of comonomer is not limited to exclusively highly solubilising moieties. Interestingly, the polymer shows a red-shifted elecroluminescence maximum (510 nm) when compared to its photoluminescence maximum (450 nm) which we attribute to excimer formation. The novel polymer was utilised as a host for a covalently- linked platinum(II) complexed porphyrin dopant. Emission from these polymers was observed in the NIR and again showed almost a 100 nm red shift from photoluminescence to electroluminescence. This work demonstrates that utilising highly aggregating host materials is an effective tool for inducing red-shifted emission in OLEDs.

A series of polyfluorene-based polymers with a range of weight percentages (w/w) of a platinum(II)-containing porphyrin, 5,15-dimesityl-10,20-diphenylporphyrinato platinum(II) (MPP(Pt)), were synthesised and incorporated into organic light-emitting diodes. All polymers showed emission predominantly in the red/NIR region with only those polymers with porphyrin w/w of less than 2% showing residual tails at wavelengths lower than 600 nm, indicating increased emission from the porphyrin as w/w increases. The 2% loading of MPP(Pt) gave the highest efficiency LED (0.48%) and light output (2630 mW/m2).

Previously, we reported interference due to several ozone-scavenging reagents (OSRs) in the quantitation of aldehydes using O-(2,3,4,5,6-pentafluorobenzyl)oxylamine (PFBOA) in the analysis of ozonated waters. Scavenging ozone is essential if ozonation byproduct concentrations are to be fixed in time, which is required in a study of formation as a function of time; otherwise, additional redox reactions can rake place prior to analysis. We have since determined that triphenylphosphine and indigo-5,5',7-trisulfonate can be satisfactory OSRs. Both PPh3 and indigo-5,5',7-trisulfonate react rapidly with ozone, i.e., within 10 s. Triphenylphosphine is insoluble in water and must be dissolved in an appropriate organic solvent (e.g., benzene) that can be dispersed into the sample. When PFBOA is added directly, several minutes must elapse to completely scavenge the ozone, making this approach unsatisfactory. Procedures for using these OSRs are described, and quantitative results are explained. Although PPh3 and indigo-5,5',7-trisulfonate produce deviations relative to controls devoid of OSRs, the biases are precise and therefore readily corrected for by subjecting calibration standards and analyte-fortified (spiked) samples to the same analytical procedure. Published by Elsevier Science Ltd.