Salzitsa Anastasova

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

This work presents the design, fabrication, and characterization of a robust 3D printed microfluidic analysis system that integrates with FDA-approved clinical microdialysis probes for continuous monitoring of human tissue metabolite levels. The microfluidic device incorporates removable needle type integrated biosensors for glucose and lactate, which are optimized for high tissue concentrations, housed in novel 3D printed electrode holders. A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip. Optimization of the channel size significantly improves the response time of the sensor. As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime.

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 (50µm 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 membrane 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.

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 within 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 in situ field trials have been carried out and are presented in this paper.

Low cost, calibration-free sensors for in situ determination of natural water pollution

One of the critical challenges for analytical sciences is the ability to perform reliable environmental monitoring at remote locations while significantly reducing per-sample and per-measurement cost. In this work, we demonstrate an approach that demonstrates production of ultra-sensitive sensors with almost identical response characteristics on a mass-scale, their integration with low-cost electronics for wireless data transmission and the use of such devices in environmental analysis

Wearable electronic sensor for potentiometric and amperometric measurements

To enable continuous monitoring of electrochemical sensors outside the laboratories, there is a significant demand on electrochemical measurement systems to be miniaturized. The paper presents a low-cost, portable miniature device for electrochemical measurements. The device consists of a 35mm × 20mm × 25mm wireless tag, which enables potentiometric and amperometric measurement, and a base station for data acquisition. Potentiometric performance is evaluated using solid contact ion selective electrodes for pH and sodium. High sensitivity, repeatability and fast response time have been achieved. Amperometric measurement of hydrogen peroxide shows that the measured current accuracy and sensitivity are comparable to that of a commercial potentiostat. Moreover, the device can be used for lactate concentration sensing.

Extreme Physiological State: Development of Tissue Lactate Sensor

Lactate is one of the most important biomarkers of tissue oxygenation and thus of paramount importance for sports and health care applications. Lactate levels provide information on anaerobic threshold which is very important for tailoring training programs in endurance sports. In this contribution we present an implantable amperometric lactate sensor for continuous in vivo monitoring. A needle based construction is used where a sensing platinum wire is inserted into a stainless steel tube that serves as a combined counter and reference electrode allowing for easy insertion, small size and minimally invasive procedure. The sensing enzyme layer is sandwiched between two polymer membranes which allow high selectivity, a wide lactate linear range and biocompatibility. The sensors have been fully evaluated in vitro and tested in vivo in rats. The measured values of tissue lactate obtained with our sensors were compared with lactate levels measured in blood by the commercial Lactate Pro analyzer. The obtained concentrations were in the same range, however, no clear correlation between blood and tissue values was found. Coldsterilisation by gamma radiation, required for human studies, is currently being investigated. This work will provide valuable information on lactate levels in different physiological compartments and increase our understanding of physiological processes related to endurance sports.

Position paper: The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical biopsy techniques — which can provide minimally invasive or noninvasive alternatives to biopsy — could offer other routes to validation and could potentially be used as point-of-care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care.

A bio-inspired 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.

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.

Electrochemical Sensor Designs for Biomedical Implants

The need to record directly the sensing target of interest in the vicinity of where a physiological and clinically relevant event takes place, rather than indirectly or through surrogate measures, has led to the need for implantable monitoring devices. In addition to ensuring the sensitivity and specificity of sensor responses, issues related to sensor fouling, drift, biocompatibility, and hermeticity of the packaging are important considerations. This chapter examines the current state of the art of sensing techniques, focusing on electrochemical methods (potentiometry, amperometry, and voltammetry), due to their simplicity in design and fabrication [1], as well as low-power operation.