Vincenzo F. Curto

Smartphone-Based Simultaneous pH and Nitrite Colorimetric Determination for Paper Microfluidic Devices

In this work, an Android application for measurement of nitrite concentration and pH determination in combination with a low-cost paper-based microfluidic device is presented. The application uses seven sensing areas, containing the corresponding immobilized reagents, to produce selective color changes when a sample solution is placed in the sampling area. Under controlled conditions of light, using the flash of the smartphone as a light source, the image captured with the built-in camera is processed using a customized algorithm for multidetection of the colored sensing areas. The developed image-processing allows reducing the influence of the light source and the positioning of the microfluidic device in the picture. Then, the H (hue) and S (saturation) coordinates of the HSV color space are extracted and related to pH and nitrite concentration, respectively. A complete characterization of the sensing elements has been carried out as well as a full description of the image analysis for detection. The results show good use of a mobile phone as an analytical instrument. For the pH, the resolution obtained is 0.04 units of pH, 0.09 of accuracy, and a mean squared error of 0.167. With regard to nitrite, 0.51% at 4.0 mg L(-1) of resolution and 0.52 mg L(-1) as the limit of detection was achieved.

Organic electrochemical transistor incorporating an ionogel as a solid state electrolyte for lactate sensing

Room temperature Ionic liquids (RTILs) have evolved as a new type of solvent for biocatalysis, mainly due to their unique and tunable physical properties.[1] In addition, within the family of organic semiconductor-based sensors, organic electrochemical transistors (OECTs) have attracted particular interest.[2] Here, we present a simple and robust biosensor, based on a OECT, capable of measuring lactic acid using a gel-like polymeric materials that endow RTIL (ionogel)[3] as solid-state electrolyte both to immobilise the enzyme and to serve as a supporting electrolyte.[4] This represents the first step towards the achievement of a fast, flexible, miniaturised and cheap way of measuring lactate concentration in sweat.

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.

Fast prototyping of paper-based microfluidic devices by contact stamping using indelible ink

Here we present a fast and cheap prototyping technique for the realisation of paper-based microfluidic devices simply by using a stamp and indelible ink. The proposed mechanism involves contact stamping of indelible ink to laboratory filter paper using a PDMS stamp, which defines the microfluidic structure. It is a cleanroom and washing steps-free method which provides a reproducible method for the production of functional paper-based microfluidic devices in a single step in less than 10 s. The method is fully characterised and the concept has been applied, as a proof-of-principle, for the realisation of a low-cost colorimetric glucose sensor.

A Microfluidic Ion Pump for In Vivo Drug Delivery

Implantable devices offer an alternative to systemic delivery of drugs for the treatment of neurological disorders. A microfluidic ion pump (µFIP), capable of delivering a drug without the solvent through electrophoresis, is developed. The device is characterized in vitro by delivering γ-amino butyric acid to a target solution, and demonstrates low-voltage operation, high drug-delivery capacity, and high ON/OFF ratio. It is also demonstrated that the device is suitable for cortical delivery in vivo by manipulating the local ion concentration in an animal model and altering neural behavior. These results show that µFIPs represent a significant step forward toward the development of implantable drug-delivery systems.

Wearable Bio and Chemical Sensors

Wearable chemical and biochemical sensors are a relatively new area of sensor research that poses unique challenges to the field of wearable sensing. The reason is that chemical sensors have a different mode of operation compared to physical transducers, and thus must be directly exposed, and interact with, specific molecular components in (usually liquid) samples. Wearable chemical and biochemical sensing has the potential to provide new sources of non-invasive physiological information through interaction with a variety of body fluids, such as sweat and interstitial fluids. This information may be used to enhance personal health through early detection of illness that in turn can trigger early interventions. There is also the potential to ensure personal safety by monitoring hazardous substances in the individual’s external environment. This chapter explains the design issues of wearable chemical sensors. Some of the main application areas of this novel technology are discussed with examples of the latest research developments.

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are two-fold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.

“Sweat-on-a-chip”: Analysing sweat in real time with disposable micro-devices

Here we present the fabrication and the performance of a novel, wearable, robust, flexible and disposable micro-fluidic device which incorporates miniature optical components as a detection system, for wireless monitoring in real time mode of sweat pH during an exercise session. This micro-fluidic platform is completely non-invasive, with the great advantage of providing a continuous flow of fresh sweat for continuous real time analysis, ensuring immediate feedback regarding sweat composition to an athlete and/or coach. To the best of our knowledge, this is the first wearable and wireless micro-fluidic device suitable for real time analysis and reporting of the wearers physiological state.

Electrochemical transistors with ionic liquids for enzymatic sensing

Over the past decade conducting polymer electrodes have played an important role in bio-sensing and actuation. Recent developments in the field of organic electronics have made available a variety of devices that bring unique capabilities at the interface with biology. One example is organic electrochemical transistors (OECTs) that are being developed for a variety of bio-sensing applications, including the detection of ions, and metabolites, such as glucose and lactate. Room temperature ionic liquids (RTILs) are organic salts, which are liquid at ambient temperature. Their nonvolatile character and thermal stability makes them an attractive alternative to conventional organic solvents. Here we report an enzymatic sensor based on an organic electro-chemical transistor with RTILs as an integral part of its structure and as an immobilization medium for the enzyme and the mediator. Further investigation shows that these platforms can be incorporated into flexible materials such as carbon cloth and can be utilized for bio-sensing. The aim is to incorporate the overall platform in a wearable sensor to improve athlete performance with regards to training. In this manuscript an introduction to ionic liquids (ILs), IL - enzyme mixtures and a combination of these novel materials being used on OECTs are presented.