Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications

Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling.

Giant magnetoresistive (GMR) sensors have been shown to be among the most sensitive biosensors reported. While high-density and scalable sensor arrays are desirable for achieving multiplex detection, scalability remains challenging because of long data acquisition time using conventional readout methods. In this paper, we present a scalable magnetoresistive biosensor array with an on-chip magnetic field generator and a high-speed data acquisition method. The on-chip field generators enable magnetic correlated double sampling (MCDS) and global chopper stabilization to suppress 1/f noise and offset. A measurement with the proposed system takes only 20 ms, approximately 50× faster than conventional frequency domain analysis. A corresponding time domain temperature correction technique is also presented and shown to be able to remove temperature dependence from the measured signal without extra measurements or reference sensors. Measurements demonstrate detection of magnetic nanoparticles (MNPs) at a signal level as low as 6.92 ppm. The small form factor enables the proposed platform to be portable as well as having high sensitivity and rapid readout, desirable features for next generation diagnostic systems, especially in point-of-care (POC) settings

Kinetic Characterisation of a Single Chain Antibody against the Hormone Abscisic Acid: Comparison with Its Parental Monoclonal

A single-chain Fv fragment antibody (scFv) specific for the plant hormone abscisic acid (ABA) has been expressed in the bacterium Escherichia coli as a fusion protein. The kinetics of ABA binding have been measured using surface plasmon resonance spectrometry (BIAcore 2000) using surface and solution assays. Care was taken to calculate the concentration of active protein in each sample using initial rate measurements under conditions of partial mass transport limitation. The fusion product, parental monoclonal antibody and the free scFv all have low nanomolar affinity constants, but there is a lower dissociation rate constant for the parental monoclonal resulting in a three-fold greater affinity. Analogue specificity was tested and structure-activity binding preferences measured. The biologically-active (+)-ABA enantiomer is recognised with an affinity three orders of magnitude higher than the inactive (-)-ABA. Metabolites of ABA including phaseic acid, dihydrophaseic acid and deoxy-ABA have affinities over 100-fold lower than that for (+)-ABA. These properties of the scFv make it suitable as a sensor domain in bioreporters specific for the naturally occurring form of ABA

The Oneiric Reality of Electronic Scents

This paper investigates the ‘oneiric’ dimension of scent, by suggesting a new design process that can be worn as a fashion accessory or integrated in textile technologies, to subtly alter reality and go beyond our senses. It fuses wearable ‘electronic scent’ delivery systems with pioneering biotechnologies as a ground-breaking ‘science fashion’ enabler. The purpose is to enhance wellbeing by reaching a day‐dream state of being through the sense of smell. The sense of smell (or olfaction) is a chemical sense and part of the limbic system which regulates emotion and memory within the brain. The power of scent makes content extremely compelling by offering a heightened sense of reality which is intensified by emotions such as joy, anger and fear. Scent helps us appreciate all the senses as we embark on a sensory journey unlike any other; it enhances mood, keeps us in the moment, diverts us from distractions, reduces boredom and encourages creativity. This paper highlights the importance of smell, the forgotten sense, and also identifies how we as humans have grown to underuse our senses. It endeavours to show how the reinvention of our sensory faculties is possible through advances in biotechnology. It introduces the new ‘data senses’ as a wearable sensory platform that triggers and fine tunes the senses with fragrances. It puts forward a new design process that is currently being developed in clothing elements, jewellery and textile technologies, offering a new method to deliver scent electronically and intelligently in fashion and everyday consumer products. It creates a personal ‘scent wave’, around the wearer, to allow the mind to wander, to give a deeper sense of life or ‘lived reality’ (verses fantasy), a new found satisfaction and confidence, and to reach new heights of creativity. By combining biology with wearable technologies, we propose a biotechnological solution that can be translated into sensory fashion elements. This is a new trend in 21st century ‘data sensing’, based on holographic biosensors that sense the human condition, aromachology (the science of the effect of fragrance and behaviour), colour-therapy, and smart polymer science. The use of biosensors in the world of fashion and textiles, enables us to act on visual cues or detect scent signals and rising stress levels, allowing immediate information to hand. An ‘oneiric’ mood is triggered by a spectrum of scents which is encased in a micro-computerised ‘scent‐cell’ and integrated into clothing elements or jewellery. When we inhale an unexpected scent, it takes us by surprise; the power of fragrance fills us with pleasurable ripples of multi‐sensations and dream‐like qualities. The aromas create a near trance‐like experience that induces a daydream state of (immediate) satisfaction, or a ‘revived reality’ in our personal scent bubble of reality. The products and jewellery items were copyrighted and designed by Slim Barrett and the technology input was from EG Technology and Epigem

Dynamics of ABC Transporter P-glycoprotein in Three Conformational States.

We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to obtain a comprehensive view of transporter dynamics (85.8% sequence coverage) occurring throughout the multidrug efflux transporter P-glycoprotein (P-gp) in three distinct conformational states: predominantly inward-facing apo P-gp, pre-hydrolytic (E552Q/E1197Q) P-gp bound to Mg+2-ATP, and outward-facing P-gp bound to Mg+2-ADP-VO4-3. Nucleotide affinity was measured with bio-layer interferometry (BLI), which yielded kinetics data that fit a two Mg+2-ATP binding-site model. This model has one high affinity site (3.2 ± 0.3 µM) and one low affinity site (209 ± 25 µM). Comparison of deuterium incorporation profiles revealed asymmetry between the changes undergone at the critical interfaces where nucleotide binding domains (NBDs) contact intracellular helices (ICHs). In the pre-hydrolytic state, both interfaces between ICHs and NBDs decreased exchange to similar extents relative to inward-facing P-gp. In the outward-facing state, the ICH-NBD1 interface showed decreased exchange, while the ICH-NBD2 interface showed less of an effect. The extracellular loops (ECLs) showed reduced deuterium uptake in the pre-hydrolytic state, consistent with an occluded conformation. While in the outward-facing state, increased ECL exchange corresponding to EC domain opening was observed. These findings point toward asymmetry between both NBDs, and they suggest that pre-hydrolytic P-gp occupies an occluded conformation

A systematic literature review of cloud computing in eHealth

Cloud computing in eHealth is an emerging area for only few years. There needs to identify the state of the art and pinpoint challenges and possible directions for researchers and applications developers. Based on this need, we have conducted a systematic review of cloud computing in eHealth. We searched ACM Digital Library, IEEE Xplore, Inspec, ISI Web of Science and Springer as well as relevant open-access journals for relevant articles. A total of 237 studies were first searched, of which 44 papers met the Include Criteria. The studies identified three types of studied areas about cloud computing in eHealth, namely (1) cloud-based eHealth framework design (n=13); (2) applications of cloud computing (n=17); and (3) security or privacy control mechanisms of healthcare data in the cloud (n=14). Most of the studies in the review were about designs and concept-proof. Only very few studies have evaluated their research in the real world, which may indicate that the application of cloud computing in eHealth is still very immature. However, our presented review could pinpoint that a hybrid cloud platform with mixed access control and security protection mechanisms will be a main research area for developing citizen centred home-based healthcare applications

Health 4.0: Applications, Management, Technologies and Review

The Industry 4.0 Standard (I4S) employs technologies for automation and data exchange through cloud computing, Big Data (BD), Internet of Things (IoT), forms of wireless Internet, 5G technologies, cryptography, the use of semantic database (DB) design, Augmented Reality (AR) and Content-Based Image Retrieval (CBIR). Its healthcare extension is the so-called Health 4.0. This study informs about Health 4.0 and its potential to extend, virtualize and enable new healthcare-related processes (e.g., home care, finitude medicine, and personalized/remotely triggered pharmaceutical treatments) and transform them into services. In the future, these services will be able to virtualize multiple levels of care, connect devices and move to Personalized Medicine (PM). The Health 4.0 Cyber-Physical System (HCPS) contains several types of computers, communications, storage, interfaces, biosensors, and bioactuators. The HCPS paradigm permits observing processes from the real world, as well as monitoring patients before, during and after surgical procedures using biosensors. Besides, HCPSs contain bioactuators that accomplish the intended interventions along with other novel strategies to deploy PM. A biosensor detects some critical outer and inner patient conditions and sends these signals to a Decision-Making Unit (DMU). Mobile devices and wearables are present examples of gadgets containing biosensors. Once the DMU receives signals, they can be compared to the patient’s medical history and, depending on the protocols, a set of measures to handle a given situation will follow. The part responsible for the implementation of the automated mitigation actions are the bioactuators, which can vary from a buzzer to the remote-controlled release of some elements in a capsule inside the patient’s body.             Decentralizing health services is a challenge for the creation of health-related applications. Together, CBIR systems can enable access to information from multimedia and multimodality images, which can aid in patient diagnosis and medical decision-making. Currently, the National Health Service addresses the application of communication tools to patients and medical teams to intensify the transfer of treatments from the hospital to the home, without disruption in outpatient services. HCPS technologies share tools with remote servers, allowing data embedding and BD analysis and permit easy integration of healthcare professionals expertise with intelligent devices.  However, it is undeniable the need for improvements, multidisciplinary discussions, strong laws/protocols, inventories about the impact of novel techniques on patients/caregivers as well as rigorous tests of accuracy until reaching the level of automating any medical care technological initiative

Vesta: A Secure and Autonomic System for Pervasive Healthcare

Accepted versio