The abundance of cellular fibronectin (c-Fn) for ischemic stroke patients and the narrow time-window (<4.5 h) for the decision to administer the thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) are challenging for the development of a point-of-care (PoC) diagnostic platform. We report a case of stratification of ischemic stroke patients based on a magnetoresistive biosensor platform that quantifies the c-Fn levels in a small volume of serum, within the clinically relevant time-window. Our PoC platform uses different ratios of biofunctionalized magnetic nanoparticles (MNPs) as immunoassay labels to adjust the sensitivity within the clinically relevant ranges for c-Fn (1-4 μg/mL). After optimizing the detection range, resolution, and sensitivity, our device was able to stratify ischemic stroke patients who developed hemorrhagic transformation, the main side-effect of rtPA, from those (both non-treated and treated with rtPA) who did not.

Bovine mastitis is an inflammation of the mammary gland caused by a multitude of pathogens with devastating consequences for the dairy industry. Global annual losses are estimated to be around €30 bn and are caused by significant milk losses, poor milk quality, culling of chronically infected animals, and occasional deaths. Moreover, mastitis management routinely implies the administration of antibiotics to treat and prevent the disease which poses serious risks regarding the emergence of antibiotic resistance. Conventional diagnostic methods based on somatic cell counts (SCC) and plate-culture techniques are accurate in identifying the disease, the respective infectious agents and antibiotic resistant phenotypes. However, pressure exists to develop less lengthy approaches, capable of providing on-site information concerning the infection, and in this way, guide, and hasten the most adequate treatment. Biosensors are analytical tools that convert the presence of biological compounds into an electric signal. Benefitting from high signal-to-noise ratios and fast response times, when properly tuned, they can detect the presence of specific cells and cell markers with high sensitivity. In combination with microfluidics, they provide the means for development of automated and portable diagnostic devices. Still, while biosensors are growing at a fast pace in human diagnostics, applications for the veterinary market, and specifically, for the diagnosis of mastitis remain limited. This review highlights current approaches for mastitis diagnosis and describes the latest outcomes in biosensors and lab-on-chip devices with the potential to become real alternatives to standard practices. Focus is given to those technologies that, in a near future, will enable for an on-farm diagnosis of mastitis.

Microvesicles (MVs) are a promising source of diagnostic biomarkers which have gained a wide interest in the biomedical and biosensing field. They can be interpreted as a "fingerprint" of various diseases. Nonetheless, MVs implementation into clinical settings has been hampered by the lack of technologies to accurately characterize, detect and quantify them. Here, we report the specific sensing and quantification of MVs from endothelial cells using a portable magnetoresistive (MR) biochip platform, in less than one hour and within physiologically relevant concentrations (1 × 108 MVs per ml). MVs were isolated from both endothelial and epithelial cells undergoing apoptosis, and characterized by atomic force microscopy (AFM) and nanoparticle tracking analysis (NTA), which revealed similar MV sizes. Importantly, our results showed that the two distinct MV populations could be discriminated with the MR biochip platform, with over a 5-fold capture efficiency of endothelial MVs in comparison to the control (epithelial MVs). Also, unspecific binding of MVs to BSA was less than 1% of the specific signal. The detection strategy was based on a sandwich immunoassay, where MVs were labelled with magnetic nanoparticles (MNPs) functionalized with Annexin V and then captured by anti-CD31 antibodies previously immobilized on the surface of the sensor. Results suggest that this approach allows the detection of specific MVs from complex samples such as serum, and highlight the potential of this technology to become a suitable tool for MVs detection as a complementary method of diagnosis.

The development of giant magnetoresistive (GMR) sensors has demonstrated significant advantages in nanomedicine, particularly for ultrasensitive point-of-care diagnostics. To this end, the detection system is required to be compact, portable, and low power consuming at the same time that a maximum signal to noise ratio is maintained. This paper reports a CMOS front-end with integrated magnetoresistive sensors for biomolecular recognition detection applications. Based on the characterization of the GMR sensor's signal and noise, CMOS building blocks (i.e., current source, multiplexers, and preamplifier) were designed targeting a negligible noise when compared with the GMR sensor's noise and a low power consumption. The CMOS front-end was fabricated using AMS [Formula: see text] technology and the magnetoresistive sensors were post-fabricated on top of the CMOS chip with high yield ( [Formula: see text]). Due to its low circuit noise (16 [Formula: see text]) and overall equivalent magnetic noise ([Formula: see text]), the full system was able to detect 250 nm magnetic nanoparticles with a circuit imposed signal-to-noise ratio degradation of only -1.4 dB. Furthermore, the low power consumption (6.5 mW) and small dimensions ([Formula: see text] ) of the presented solution guarantees the portability of the detection system allowing its usage at the point-of-care.

Portable analytical devices are notably gaining relevance in the panorama of urgent testing. Such devices have the potential to play an important role as easy-to-handle tools in critical situations. Epidemic infectious disease agents (e.g., Ebola virus, Coronavirus, Zika virus) could be controlled more easily by testing travelers on-site at the country borders to prevent outbreaks from spreading. The increasing incidence of hospital-acquired infections caused by antibiotic resistant pathogens could be minimized by point-of-care microbial analysis as well as rapid screening tests of bacteria resistance. The threat of bioterrorism using novel unknown bioweapons has never been so high, thus, in-the-field early identification of the biological agent is crucial for triggering a coordinated response. Food allergies are a growing public health concern-allergic reactions can result in anaphylactic shock, which can prove fatal in minutes-thus, the ability to test foods for common allergens, rapidly and locally, before ingestion, would improve food safety for those with allergies. Lab-on-chip devices are becoming widely available for diverse applications and are becoming increasingly affordable. However, to shrink in price and size simultaneously, some trade-offs must be made. In this Perspective, we present considerations about product specifications, design concepts, and application scenarios.

This paper reports a monolithic device integrating a CMOS analog front-end and an array of 192 MR sensors for biomolecular recognition detection. Innovative CMOS building blocks (i.e. current source, multiplexers and pre-amplifier) were designed targeting a negligible noise when compared with the MR sensors noise and a low power consumption. The CMOS front-end was fabricated using AMS 0.35 μm technology and the magnetoresistive sensors were post-fabricated on top of the CMOS chip. Due to its low noise (16 nV/√Hz), the full system was able to detect magnetic nanoparticles with a SNR degradation of only 1.4 dB (circuit imposed). Furthermore, the unprecedented low power consumption (6.5 mW) and small dimensions (7.59 mm 2 ) of the presented solution guarantees the portability of the detection system allowing its usage at the point-of-care.

This paper presents a neuronal signal detector for biologically generated magnetic fields. The system includes a hardware section implemented with discrete electronics, which has an ultralow-noise dc or dc+ac current source for magnetoresistive sensor biasing, and signal amplification and filtering, and a software interface that allows signal demodulation, visualization, and digital postprocessing. Compared with the previous measurement setup, the results show that, for the same bandwidth, the proposed instrumentation system has approximately 50 times better noise performance, making the sensor noise the dominant noise source. The system is able to record the magnetic field generated by ionic currents from action potentials of in vitro experiments with mice brain slices. In addition, to obtain an increased spatial resolution, by scaling the number of sensors that can be read, and to enhance the system immunity to external interferences, two integrated circuits with an ultralow-noise current source for MR biasing and a low-noise variable gain amplifier were developed and are also presented.

A novel multi-channel high performance embedded system capable of high throughput biological analysis is proposed in this paper. Despite other integrated lab-on-chip solutions based on magnetoresistive biochips have already been developed, they lack the scalability and computational resources to cope with new biochip designs featuring more than 1000 sensors. A new configurable acquisition and processing architecture is proposed, combining dedicated coprocessors to perform signal filtering and other computational demanding tasks, with a central processor controlling the whole system. The mapping of the architecture into a Zynq SoC demonstrated its ability to support 8 times more sensors, while ensuring a sampling frequency 1000+ times higher than the previous platforms. Furthermore, the Zynq reconfiguration abilities provide a mechanism to adapt the processing and maximize the biological sensitivity.

This paper presents an instrumentation system based on magnetoresistive sensors for neuronal signal detection. The system includes a hardware section, which provides ultra-low noise magnetoresistive sensor biasing, signal amplification and filtering, and a software interface that allows signal visualizations and digital post processing. The results show that, compared to the current measurement setup, the proposed instrumentation system increases the measurement bandwidth from 70 Hz to 2.75 kHz, and reduces the integrated noise in the signal bandwidth from 1 μVRMS to 814 nVRMS.

Since 2006, fully scalable matrix-based magnetoresistive biochips have been proposed. This integration was initially achieved with thin film switching devices and moved to complementary metal-oxide-semiconductor (CMOS) switching devices and electronics. In this paper, a new microfabrication process is proposed to integrate magnetoresistive sensors on a small CMOS chip (4 mm2). This chip includes a current generator, multiplexers, and a diode in series with a spin valve as matrix element. In this configuration, it is shown that the fabricated spin-valves have similar magnetic characteristics when compared to standalone spin valves. This validates the successfulness of the developed microfabrication process. The noise of each matrix element is further characterized and compared to the noise of a standalone spin valve and a portable electronic platform designed to perform biological assays. Although the noise is still higher, the spin valve integrated on the CMOS chip enables an increase in density and compactness of the measuring electronics.

Full Wheatstone Bridge incorporating a serially connected ensemble of Magnetic tunnel junctions was produced, targeting an application as a magnetic field compass. To that end, MTJs with RxA ~ 10kΩ μm2 TMR~150-200%, Hf = 5 Oe and Hf = 5 Oe were produced. In order to achieve a full bridge signal, two stacks with an asymmetric SAF reference structure where used to produce MTJs with opposite dR/dH upon annealing in the same substrate. The resulting Bridges exhibit sensitivities between 13.5-32 mV/V/Oe depending on the field range and provide a significantly advantageous alternative to AMR and GMR based bridges.

Several courses on embedded systems have been planned and taught to students in Electrical Engineering and Computer Science Master's programs. The tutorials play an important role in these courses, not only to motivate the students, but also to expose them to the difficulties and challenges of designing real embedded systems. This paper presents a complete lab project used over the last 15 years in a semester-long course on embedded systems that, for historical reasons, was titled Computer Electronics. This project involves all the topics studied in this course, namely programmable, configurable and dedicated processors, memory technology and organization, peripherals, and the design and implementation of complete embedded systems. Targeting image processing as a case study, in this lab project students use field programmable gate arrays (FPGAs) to design real-time embedded systems based on soft-cores, hardware accelerators, and specific input and output peripherals. Analyzing the results over the last years, it can be concluded that the inclusion of this transversal lab project boosts the interest in this Master's course and encourages the students to learn the topics required to design real embedded systems.

A self-powered hybrid sensor integrating a resonant antenna with a magnetoresistive spin valve sensor was microfabricated. The device is activated by a radiofrequency (rf) external electromagnetic source. This hybrid sensor is capable of detecting dc and ac external magnetic fields in the thermal noise regime. For an excitation rf field of 17 dB m at 130 MHz, the sensitivity to a transverse magnetic field normalized by the current induced in the device was 812 V (T A)(-1) for dc magnetic field detection and 918 V (T A)(-1) for the ac field measurement. (C) 2011 American Institute of Physics. [doi:10.1063/1.3562340]

A self-powered, hybrid sensor integrating a resonant microfabricated antenna with a spin valve sensor was fabricated. The device was activated by a radio frequency (RF) external electromagnetic source. This hybrid device was designed to behave as a series resonant circuit at 130 MHz. The self-powered sensor (powered by the RF field through the antenna) was capable of measuring the amplitude of the perpendicular RF excitation field crossing the antenna, down to 2.5 μT when excited with a RF field of 130 MHz.

This paper proposes techniques for the extraction of biological information in a recently developed handheld biochip-based microsystem. The microsystem is based on a magnetoresistive array biochip composed of a number of sensing sites with magnetic tunneling junctions (MTJ) and diodes. Different techniques are addressed to drive the MTJs with different types of signals. Different filtering strategies that allow the recovery of biological signals from the noise without overly increasing either the time required for accessing the sensors or the power consumption of the board are proposed. Finally, new techniques and algorithms are proposed to deal with the variability of the fabrication parameters of the MTJ and the diodes. Experiments with the system in a setup to detect actual biological signals are presented with encouraging results.

Faster, more sensitive and easy to operate biosensing devices still are a need at important areas such as biomedical diagnostics, food control and environmental monitoring. Recently, spintronic-devices have emerged as a promising alternative to the existent technologies [1-3]. A number of advantages, namely high sensitivity, easy integration, miniaturization, scalability, robustness and low cost make these devices potentially capable of responding to the existent technological need.