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

Smart implanted access port catheter for therapy intervention with pH and lactate biosensors.

Totally implanted access ports (TIAP) are widely used with oncology patients requiring long term central venous access for the delivery of chemotherapeutic agents, infusions, transfusions, blood sample collection and parenteral nutrition. Such devices offer a significant improvement to the quality of life for patients and reduced complication rates, particularly infection, in contrast to the classical central venous catheters. Nevertheless, infections do occur, with biofilm formation bringing difficulties to the treatment of infection-related complications that can ultimately lead to the explantation of the device. A smart TIAP device that is sensor-enabled to detect infection prior to extensive biofilm formation would reduce the cases for potential device explantation, whereas biomarkers detection within body fluids such as pH or lactate would provide vital information regarding metabolic processes occurring inside the body. In this paper, we propose a novel batteryless and wireless device suitable for the interrogation of such markers in an embodiment model of an TIAP, with miniature biochemical sensing needles. Device readings can be carried out by a smartphone equipped with Near Field Communication (NFC) interface at relative short distances off-body, while providing radiofrequency energy harvesting capability to the TIAP, useful for assessing patient's health and potential port infection on demand

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

3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate

We thank the EPSRC (EP/H009744/1) and Wellcome Trust DOH (HICF-0510-080) for fundin

Monitoring of lactate in interstitial fluid, saliva and sweat by electrochemical biosensor: the uncertainties of biological interpretation

Lactate electrochemical biosensors were fabricated using Pediococcus sp lactate oxidase (E.C. 1.1.3.2), an external polyurethane membrane laminate diffusion barrier and an internal ionomeric polymer barrier (sulphonated polyether ether sulphone polyether sulphone, SPEES PES). In a needle embodiment, a Pt wire working electrode was retained within stainless steel tubing serving as pseudoreference. The construct gave linearity to at least 25 mM lactate with 0.17 nA/mM lactate sensitivity. A low permeability inner membrane was also unexpectedly able to increase linearity. Responses were oxygen dependent at pO2 < 70 mmHg, irrespective of the inclusion of an external diffusion barrier membrane. Subcutaneous tissue was monitored in Sprague Dawley rats, and saliva and sweat during exercise in human subjects. The tissue sensors registered no response to intravenous Na lactate, indicating a blood-tissue lactate barrier. Salivary lactate allowed tracking of blood lactate during exercise, but lactate levels were substantially lower than those in blood (0–3.5 mM vs. 1.6–12.1 mM), with variable degrees of lactate partitioning from blood, evident both between subjects and at different exercise time points. Sweat lactate during exercise measured up to 23 mM but showed highly inconsistent change as exercise progressed. We conclude that neither tissue interstitial fluid nor sweat are usable as surrogates for blood lactate, and that major reappraisal of lactate sensor use is indicated for any extravascular monitoring strategy for lactate

Wireless ion selective electrode autonomous sensing system

A paradigm shift in sensing methods and principles is required to meet the legislative demands for detecting hazardous substances in the molecular world. This will encompass the development of new sensing technologies capable of performing very selective and sensitive measurements at an acceptable cost, developed by multidisciplinary teams of chemists, engineers and computer scientists to harvest information from a multitude of molecular targets in health, food and the environment. In this study we present the successful implementation of a low-cost, wireless chemical sensing system that employs a minimum set of components for effective operation. Specifically, our efforts resulted in a wireless, tri-electrode, ISE pH sensor for use in environmental monitoring. Sensor calibration and validated insitu field trials have been carried out and are presented in this paper

High temporal resolution delayed analysis of clinical microdialysate streams

We thank the Wellcome Trust DOH (HICF-0510-080), the EPSRC (EP/H009744/1) (cycling experiments), and the Imperial Confidence in Concept scheme, Ovarian Cancer Action UK (ovarian tissue measurements), the National Science Foundation (CHE-1608757), and the NIH (R01 MH104386) for fundin

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