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Nosocomial or hospital‐acquired infections (HAIs) have a major impact on mortality worldwide. Enterococcus and Staphylococcus are among the leading causes of HAIs and thus are important pathogens to control mainly due to their increased antibiotic resistance. The gold‐standard diagnostic methods for HAIs are time‐consuming, which hinders timely and adequate treatment. Therefore, the development of fast and accurate diagnostic tools is an urgent demand. In this study, we combined the sensitivity of magnetoresistive (MR) sensors, the portability of a lab‐on‐chip platform, and the specificity of phage receptor binding proteins (RBPs) as probes for the rapid and multiplex detection of Enterococcus and Staphylococcus. For this, bacterial cells were firstly labelled with magnetic nanoparticles (MNPs) functionalized with RBPs and then measured on the MR sensors. The results indicate that the RBP‐MNPS provided a specific individual and simultaneous capture of more than 70% of Enterococcus and Staphylococcus cells. Moreover, high signals from the MR sensors were obtained for these samples, providing the detection of both pathogens at low concentrations (10 CFU/ml) in less than 2 h. Overall, the lab‐on‐chip MR platform herein presented holds great potential to be used as a point‐of‐care for the rapid, sensitive and specific multiplex diagnosis of bacterial infections. [ABSTRACT FROM AUTHOR]

Biomedical applications and point-of-use devices often rely on nanoparticle concentration strategies. In this paper, on-chip magnetic trapping and manipulation of 300–500 nm superparamagnetic nanoparticles are achieved using thin-film planar circular copper coils. The trap configuration combining a central coil surrounded by four other coils, all connected in series, successfully enables simultaneous attraction and repulsion, enhancing concentration of magnetic nanoparticle (MNP). The simultaneous attraction and repulsion has advantages over static permanent magnets, where unidirectional actuation allows either attraction or repulsion. Because the distance between traps and the MNP is large (hundred micrometer), large electric currents up to 500 mA are needed to achieve fields of the order of hundreds of microtesla, which requires thermal management. Joule heating is effectively tackled by resorting to a novel cooling scheme comprising triangular microchannels milled onto copper substrates. Experimental results combining thermal surface mapping, magnetic field mapping, and optical (fluorescence microscope) observations could validate the trapping efficacy of Estapor microspheres functionalized with BODIPY 515 fluorophores. [ABSTRACT FROM AUTHOR]

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 $\mathrm{{\text{0.35}}\;\mu{\text{m}}} technology and the magnetoresistive sensors were post-fabricated on top of the CMOS chip with high yield ( \text97.9\%). Due to its low circuit noise (16 \mathrm\textnV/\sqrt\textHz) and overall equivalent magnetic noise ( $\mathrm{{\text{11.5}}\;{\text{nT}}/\sqrt{{\text{Hz}}}}$), the full system was able to detect 250 nm magnetic nanoparticles with a circuit imposed signal-to-noise ratio degradation of only $-$1.4 dB. Furthermore, the low power consumption (6.5 mW) and small dimensions ($\mathrm{{\text{7.59: mm}}^{2}}$ ) of the presented solution guarantees the portability of the detection system allowing its usage at the point-of-care. [ABSTRACT FROM PUBLISHER]

The bacterial infection degree of a real biological sample can be determined by using magnetoresistive (MR) cytometry. In this case, it is required to count detection events and to precisely determine the bacterial cells concentration detected by the sensor in each detection event. Here, we are proposing a method to evaluate the bacterial concentration from experimental obtained data. By simulating and analyzing the signals created by clusters with a different number of cells, shapes, and orientations relative to the sensor sensitive direction, clusters that can fit the experimental signals are found. The simulation results are compared with the experimental obtained signals in order to quantify the number of cells that are detected by the MR sensor in different detection events. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

In the pursuit of point-of-care systems that present high sensitivity and fast turnaround time, lateral flow is considered a remarkable promising class of in vitro diagnostics, and popularized by the pregnancy tests. A variety of lateral flow tests have emerged able to provide cardiac panels in emergency conditions, infectious disease screening, drug abuse, among others. However, most commercial tests only provide qualitative results, limiting their applicability for quantification thresholds of most biomarkers. In this paper, we propose a novel detection architecture for quantification of biomolecules labeled with magnetic nanoparticles employing two spin valve sensors. The main goal of this paper is to demonstrate that this architecture can detect and monitor MNPs flowing in a LFT strip for detection and quantification of different solutions varying in MNP concentration. In addition, we present preliminary analytical results that support our strategy for achieving biomolecular quantification using the proposed solution. [ABSTRACT FROM AUTHOR]

Highly sensitive nanosensors with high spatial resolution provide the necessary features for high-accuracy imaging of isolated magnetic nanoparticles or mapping of magnetic fields. Here, we fabricated nanosensor devices based on MgO-magnetic tunnel junctions with soft pinned sensing layer. The exchange interaction at the free-layer is tuned to yield distinct linear operation ranges for the nanosensors. Circular (diameter D = 120–500 nm) and elliptical pillars with low aspect ratio (120 nm \times 130 nm–120 nm \times 200 nm) displaying a linear non-hysteretic transfer curves with tunnel magnetoresistance values up to 143% were obtained. A noticeable improvement in the sensitivity for circular structures from an average value of \sim 1 %/mT up to \sim 2 Hz with Hooge parameters within 1– 3 \times 10^{-9} \mu m ^{2}$ in the linear range. Nevertheless, such high sensitivity values are a major improvement in comparison with those reported previously for nanometric sensors, and extremely competitive with values reported for micrometric spin-valve sensors, with the advantage of providing a reduced device footprint suitable for highly resolved measurements. [ABSTRACT FROM AUTHOR]

This paper presents a prototype of a platform for biomolecular recognition detection. The system is based on a magnetoresistive biochip that performs biorecognition assays by detecting magnetically tagged targets. All the electronic circuitry for addressing, driving and reading out signals from spin-valve or magnetic tunnel junctions sensors is implemented using off-the-shelf components. Taking advantage of digital signal processing techniques, the acquired signals are processed in real time and transmitted to a digital analyzer that enables the user to control and follow the experiment through a graphical user interface. The developed platform is portable and capable of operating autonomously for nearly eight hours. Experimental results show that the noise level of the described platform is one order of magnitude lower than the one presented by the previously used measurement set-up. Experimental results also show that this device is able to detect magnetic nanoparticles with a diameter of 250 nm at a concentration of about 40 fM. Finally, the biomolecular recognition detection capabilities of the platform are demonstrated by performing a hybridization assay using complementary and non-complementary probes and a magnetically tagged 20mer single stranded DNA target. [ABSTRACT FROM AUTHOR]

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. Cellular fibronectin (c-Fn) is a predictive biomarker for evaluating the risk–benefit of the thrombolytic treatment for ischemic stroke. Present in abundance in the serum of stroke patients, c-Fn is used in this work as a model of challenges encountered in developing biosensors for clinical assays. The systematic optimization of the detection range, resolution, and sensitivity of the assay according to the clinical needs is demonstrated in this investigation. The use of magnetic labels and their versatility when coupled with a portable point-of-care magnetoresistive platform allowed patient stratification in less than 2 h. Unlabelled Image [ABSTRACT FROM AUTHOR]

Tuberculosis is one of the major public health concerns. This highly contagious disease affects more than 10.4 million people, being a leading cause of morbidity by infection. Tuberculosis is diagnosed at the point-of-care by the Ziehl-Neelsen sputum smear microscopy test. Ziehl-Neelsen is laborious, prone to human error and infection risk, with a limit of detection of 10 4 cells/mL. In resource-poor nations , a more practical test, with lower detection limit, is paramount. This work uses a magnetoresistive biosensor to detect BCG bacteria for tuberculosis diagnosis. Herein we report: i) nanoparticle assembly method and specificity for tuberculosis detection; ii) demonstration of proportionality between BCG cell concentration and magnetoresistive voltage signal; iii) application of multiplicative signal correction for systematic effects removal; iv) investigation of calibration effectiveness using chemometrics methods; and v) comparison with state-of-the-art point-of-care tuberculosis biosensors. Results present a clear correspondence between voltage signal and cell concentration. Multiplicative signal correction removes baseline shifts within and between biochip sensors, allowing accurate and precise voltage signal between different biochips. The corrected signal was used for multivariate regression models, which significantly decreased the calibration standard error from 0.50 to 0.03 log 10 (cells/mL). Results show that Ziehl-Neelsen detection limits and below are achievable with the magnetoresistive biochip, when pre-processing and chemometrics are used. [ABSTRACT FROM AUTHOR]