Multi-Parametric Rigid and Flexible, Low-Cost, Disposable Sensing Platforms for Biomedical Applications

The measurement of Na+, K+ and H+ is essential in medicine and plays an important role in the assessment of tissue ischemia. Microfabrication, inkjet- and screen-printing can be used for solid contact ion selective electrodes (ISE) realization; these, however, can be non-standardized, costly and time consuming processes. We present the realization of ISEs on post-processed electrodes fabricated via standardized printed circuit board (PCB) manufacturing techniques. In vitro results are presented from two rigid platforms (32 ISEs) for liquid sample dip-stick measurements and two flexible platforms (6 and 32 ISEs) for post-surgical intestinal tissue monitoring, each with a common reference electrode (RE). These are combined with optimized tetrapolar bioimpedance sensors for tissue ischemia detection. Both electroless and hard gold PCB finishes are examined. Apart from the electroless rigid platform, the rest demonstrated comparable and superior performance, with the pH sensors demonstrating the greatest deviation; the flexible hard gold platform achieved a sensitivity 4.6 mV/pH and 49.2 mV/pH greater than the electroless flexible and rigid platforms, respectively. The best overall performance was achieved with the hard gold flexible platform with sensitivities as large as 73.4 mV/pH, 56.3 mV/log [Na+], and 57.4 mV/log [K+] vs. custom REs on the same substrate. Simultaneous measurements of target analytes is demonstrated with test solutions and saliva samples. The results exhibit superior performance to other PCB-based pH sensors, demonstration of Na+ and K+ PCB-based sensors with comparable performance to potentiometric sensors fabricated with other techniques, paving the way towards mass-produced, low-cost, disposable, multi-parametric chemical sensing diagnostic platforms

Development of chitosan, pullulan, and alginate based drug-loaded nano-emulsions as a potential malignant melanoma delivery platform

Melanoma is the most aggressive form of skin cancer and various treatments have been investigated to treat this disease, but drug resistance remains an important factor in the failure of conventional therapeutics. Here we describe the development, optimisation and characterisation of alginate, chitosan, pullulan, and their combined nano-emulsions as drug delivery platforms for potential application for melanoma. A novel nano-emulsion delivery system was designed and assessed by determining in vitro drug release, cell viability (MTT), cellular apoptosis (ELISA) and confocal microscopy. A comparative analysis of the effect of the nano-emulsions on BRAF-mutant melanoma (A375) and keratinocyte (HaCaT) cells was conducted, with the “pullulan-chitosan” nano-emulsion chosen as an approach for melanoma drug delivery. Increased apoptosis induction of melanoma cells was recorded as 90% after 72 h of treatment with doxorubicin-loaded optimal nano-emulsion. Similarly, in the same treatment, the viability of melanoma cells was decreased by 70%. More importantly, A375 cells treated with naïve doxorubicin were 100% viable compared to cells treated with doxorubicin-loaded nano-emulsion which were only 30%viable. Achieved results are indicating the importance of the drug carrier’s polymeric combination and the impact of the drug release pattern on the efficiency of the treatment. This offers potential for the abrogation of drug- efflux-related chemo-resistance

A Wearable Multisensing Patch for Continuous Sweat Monitoring

In sport, exercise and healthcare settings, there is a need for continuous, non-invasive monitoring of biomarkers to assess human performance, health and wellbeing. Here we report the development of a flexible microfluidic platform with fully integrated sensing for on-body testing of human sweat. The system can simultaneously and selectively measure metabolite (e.g. lactate) and electrolytes (e.g. pH, sodium) together with temperature sensing for internal calibration. The construction of the platform is designed such that continuous flow of sweat can pass through an array of flexible microneedle type of sensors (50 µm diameter) incorporated in a microfluidic channel. Potentiometric sodium ion sensors were developed using a polyvinyl chloride (PVC) functional membrane deposited on an electrochemically deposited internal layer of Poly(3,4-ethylenedioxythiophene) (PEDOT) polymer. The pH sensing layer is based on a highly sensitive membrane of iridium oxide (IrOx). The amperometric-based lactate sensor consists of doped enzymes deposited on top of a semipermeable copolymer mebrane and outer polyurethane layers. Real-time data were collected from human subjects during cycle ergometry and treadmill running. A detailed comparison of sodium, lactate and cortisol from saliva is reported, demonstrating the potential of the multi-sensing platform for tracking these outcomes. In summary, a fully integrated sensor for continuous, simultaneous and selective measurement of sweat metabolites, electrolytes and temperature was achieved using a flexible microfluidic platform. This system can also transmit information wirelessly for ease of collection and storage, with the potential for real-time data analytics

Solid-state reference electrodes based on carbon nanotubes and polyacrylate membranes

A novel potentiometric solid-state reference electrode containing single-walled carbon nanotubes as the transducer layer between a polyacrylate membrane and the conductor is reported here. Single-walled carbon nanotubes act as an efficient transducer of the constant potentiometric signal originating from the reference membrane containing the Ag/AgCl/Cl− ions system, and they are needed to obtain a stable reference potentiometric signal. Furthermore, we have taken advantage of the light insensitivity of single-walled carbon nanotubes to improve the analytical performance characteristics of previously reported solid-state reference electrodes. Four different polyacrylate polymers have been selected in order to identify the most efficient reservoir for the Ag/AgCl system. Finally, two different arrangements have been assessed: (1) a solid-state reference electrode using photo-polymerised n-butyl acrylate polymer and (2) a thermo-polymerised methyl methacrylate:n-butyl acrylate (1:10) polymer. The sensitivity to various salts, pH and light, as well as time of response and stability, has been tested: the best results were obtained using single-walled carbon nanotubes and photo-polymerised n-butyl acrylate polymer. Water transport plays an important role in the potentiometric performance of acrylate membranes, so a new screening test method has been developed to qualitatively assess the difference in water percolation between the polyacrylic membranes studied. The results presented here open the way for the true miniaturisation of potentiometric systems using the excellent properties of single-walled carbon nanotubes

A bioinspired 3D micro-structure for graphene-based bacteria sensing

Nature is a great source of inspiration for the development of solutions for biomedical problems. We present a novel biosensor design utilizing two-photon polymerisation and graphene to fabricate an enhanced biosensing platform for the detection of motile bacteria. A cage comprising venous valve-inspired directional micro-structure is fabricated around graphene-based sensing electronics. The asymmetric 3D micro-structure promotes motile cells to swim from outside the cage towards the inner-most chamber, resulting in concentrated bacteria surrounding the central sensing region, thus enhancing the sensing signal. The concentrating effect is proved across a range of cell cultures - from 101 CFU/ml to 109 CFU/ml. Fluorescence analysis shows a 3.38–3.5 times enhanced signal. pH sensor presents a 2.14–3.08 times enhancement via the detection of cellar metabolite. Electrical measurements demonstrate an 8.8–26.7 times enhanced current. The proposed platform provides a new way of leveraging bio-inspired 3D printing and 2D materials for the development of sensing devices for biomedical applications

Towards a fully automatic food intake recognition system using acoustic, image capturing and glucose measurements

Food intake is a major healthcare issue in developed countries that has become an economic and social burden across all sectors of society. Bad food intake habits lead to increased risk for development of obesity in children, young people and adults, with the latter more prone to suffer from health diseases such as diabetes, shortening the life expectancy. Environmental, cultural and behavioural factors have been appointed to be responsible for altering the balance between energy intake and expenditure, resulting in excess body weight. Methods to counteract the food intake problem are vast and include self-reported food questionnaires, body-worn sensors that record the sound, pressure or movements in the mouth and GI tract or image-based approaches that recognize the different types of food being ingested. In this paper we present an ear-worn device to track food intake habits by recording the acoustic signal produced by the chewing movements as well as the glucose level amperiometrically. Combined with a small camera on a future version of the device, we hope to deliver a complete system to control dietary habits with caloric intake estimation during satiation and deficit during satiety periods, which can be adapted to the physiology of each user

A monolithic force-sensitive 3D microgripper fabricated on the tip of an optical fiber using 2-photon polymerization

Microscale robotic devices have myriad potential applications including drug delivery, biosensing, cell manipulation, and microsurgery. In this work, a tethered, 3D, compliant grasper with an integrated force sensor is presented, the entirety of which is fabricated on the tip of an optical fiber in a single-step process using 2-photon polymerization. This gripper can prove useful for the interrogation of biological microstructures such as alveoli, villi, or even individual cells. The position of the passively actuated grasper is controlled via micromanipulation of the optical fiber, and the microrobotic device measures approximately 100 µm in length and breadth. The force estimation is achieved using optical interferometry: high-dimensional spectral readings are used to train artificial neural networks to predict the axial force exerted on/by the gripper. The design, characterization, and testing of the grasper are described and its real-time force-sensing capability with an accuracy below 2.7% of the maximum calibrated force is demonstrated