NFC-Powered Implantable Device for On-Body Parameters Monitoring With Secure Data Exchange Link to a Medical Blockchain Type of Network.

Implantable devices represent the future of remote medical monitoring and administration of both chemical and physical therapies to the patients. Although some of these devices are already in the market, the security mechanisms deployed inside them to withstand deliberate external influence are still decades away from the robust digital data security schemes employed in modern distributed networks these days. Medical data theft, spoofing, and disclosure pose serious threats that can ultimately lead to individual and social stigmas or even death. In this article, we present a small-form and batteryless implantable device with acquisition channels for biopotential (30-dB gain and 16-Hz bandwidth), arterial pulse oximetry, and temperature (0.12°C accuracy) recordings, suitable for cardiovascular, neuronal, and endocrine parameters assessment. The proposed device is powered by the near-field communication (NFC) interface with an external mobile phone, with a power consumption of 0.9 mW and achieving the full operation for distances close to 1 cm under the skin. In situ encryption of the acquired physiological signals is performed by a lightweight and short-term symmetric-key distribution scheme with data stream hopping, in order to ensure secure data transference over the air between the patient and trusted entities only, complemented by data storage, processing, and recovery through a medical blockchain type of network that involves the main stakeholders inside a medical community.

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.

Rapid uropathogen identification using surface enhanced Raman spectroscopy active filters.

Urinary tract infection is one of the most common bacterial infections leading to increased morbidity, mortality and societal costs. Current diagnostics exacerbate this problem due to an inability to provide timely pathogen identification. Surface enhanced Raman spectroscopy (SERS) has the potential to overcome these issues by providing immediate bacterial classification. To date, achieving accurate classification has required technically complicated processes to capture pathogens, which has precluded the integration of SERS into rapid diagnostics. This work demonstrates that gold-coated membrane filters capture and aggregate bacteria, separating them from urine, while also providing Raman signal enhancement. An optimal gold coating thickness of 50 nm was demonstrated, and the diagnostic performance of the SERS-active filters was assessed using phantom urine infection samples at clinically relevant concentrations (105 CFU/ml). Infected and uninfected (control) samples were identified with an accuracy of 91.1%. Amongst infected samples only, classification of three bacteria (Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae) was achieved at a rate of 91.6%.

Towards Wearable and Flexible Sensors and Circuits Integration for Stress Monitoring.

Excessive stress is one of the main causes of mental illness. Long-term exposure of stress could affect one's physiological wellbeing (such as hypertension) and psychological condition (such as depression). Multisensory information such as heart rate variability (HRV) and pH can provide suitable information about mental and physical stress. This paper proposes a novel approach for stress condition monitoring using disposable flexible sensors. By integrating flexible amplifiers with a commercially available flexible polyvinylidene difluoride (PVDF) mechanical deformation sensor and a pH-type chemical sensor, the proposed system can detect arterial pulses from the neck and pH levels from sweat located in the back of the body. The system uses organic thin film transistor (OTFT)-based signal amplification front-end circuits with modifications to accommodate the dynamic signal ranges obtained from the sensors. The OTFTs were manufactured on a low-cost flexible polyethylene naphthalate (PEN) substrate using a coater capable of Roll-to-Roll (R2R) deposition. The proposed system can capture physiological indicators with data interrogated by Near Field Communication (NFC). The device has been successfully tested with healthy subjects, demonstrating its feasibility for real-time stress monitoring.

Carbon-Nanotube-Coated 3D Microspring Force Sensor for Medical Applications.

Flexible electronic materials combined with micro-3D fabrication present new opportunities for wearable biosensors and medical devices. This Research Article introduces a novel carbon-nanotube-coated force sensor, successfully combining the advantages of flexible conductive nanomaterials and the versatility of two photon polymerization technologies for creating functional 3D microstructures. The device employs carbon-nanotube-coated microsprings with varying configurations and geometries for  real-time force sensing. To demonstrate its practical value, the device has first been embodied as a patch sensor for transcutaneous monitoring of human arterial pulses, followed by the development of a multiple-point force-sensitive catheter for real-time noninvasive intraluminal intervention. The results illustrate the potential of leveraging advanced nanomaterials and micro-3D-printing for developing new medical devices.

A Smart Wireless Ear-Worn Device for Cardiovascular and Sweat Parameter Monitoring During Physical Exercise: Design and Performance Results.

Wearable biomedical technology has gained much support lately as devices have become more affordable to the general public and they can easily interact with mobile phones and other platforms. The feasibility and accuracy of the data generated by these devices so as to replace the standard medical methods in use today is still under scrutiny. In this paper, we present an ear-worn device to measure cardiovascular and sweat parameters during physical exercise. ECG bipolar recordings capture the electric potential around both ears, whereas sweat rate is estimated by the impedance method over one segment of tissue closer to the left ear, complemented by the measurement of the lactate and pH levels using amperiometric and potentiometric sensors, respectively. Together with head acceleration, the acquired data is sent to a mobile phone via BLE, enabling extended periods of signal recording. Results obtained by the device have shown a SNR level of 18 dB for the ECG signal recorded around the ears, a THD value of -20.46 dB for the excitation signal involved in impedance measurements, sweat conductivity of 0.08 S/m at 1 kHz and sensitivities of 50 mV/pH and 0.8 µA/mM for the pH and lactate acquisition channels, respectively. Testing of the device was performed in human subjects during indoors cycling with characteristic level changes.

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.

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 4.6mV/pH and 49.2mV/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 73.4mV/pH, 56.3mV/log [Na+], and 57.4mV/log [K+] vs. custom REs on the same substrate. Simultaneous measurement of target analytes is demonstrated with test solutions and saliva samples. The results demonstrate superior performance to other PCB-based pH sensors and 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.

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 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.

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.

Chemosensors and biosensors based on polyelectrolyte microcapsules containing fluorescent dyes and enzymes.

The concept of enzyme-assisted substrate sensing based on use of fluorescent markers to detect the products of enzymatic reaction has been investigated by fabrication of micron-scale polyelectrolyte capsules containing enzymes and dyes in one entity. Microcapsules approximately 5 µm in size entrap glucose oxidase or lactate oxidase, with peroxidase, together with the corresponding markers Tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) dichloride (Ru(dpp)) complex and dihydrorhodamine 123 (DHR123), which are sensitive to oxygen and hydrogen peroxide, respectively. These capsules are produced by co-precipitation of calcium carbonate particles with the enzyme followed by layer-by-layer assembly of polyelectrolytes over the surface of the particles and incorporation of the dye in the capsule interior or in the multilayer shell. After dissolution of the calcium carbonate the enzymes and dyes remain in the multilayer capsules. In this study we produced enzyme-containing microcapsules sensitive to glucose and lactate. Calibration curves based on fluorescence intensity of Ru(dpp) and DHR123 were linearly dependent on substrate concentration, enabling reliable sensing in the millimolar range. The main advantages of using these capsules with optical recording is the possibility of building single capsule-based sensors. The response from individual capsules was observed by confocal microscopy as increasing fluorescence intensity of the capsule on addition of lactate at millimolar concentrations. Because internalization of the micron-sized multi-component capsules was feasible, they could be further optimized for in-situ intracellular sensing and metabolite monitoring on the basis of fluorescence reporting.