FTA-LAMP based biosensor for a rapid in-field detection of Globodera pallida-the pale potato cyst nematode.

The combination of a sensitive and specific magnetoresistive sensing device with an easy DNA extraction method and a rapid isothermal amplification is presented here targeting the on-site detection of Globodera pallida, a potato endoparasitic nematode. FTA-cards were used for DNA extraction, LAMP was the method developed for DNA amplification and a nanoparticle functionalized magnetic-biosensor was used for the detection. The combinatorial effect of these three emerging technologies has the capacity to detect G. pallida with a detection limit of one juvenile, even when mixed with other related species. This combined system is far more interesting than what a single technology can provide. Magnetic biosensors can be combined with any DNA extraction protocol and LAMP forming a new solution to target G. pallida. The probe designed in this study consistently distinguished G. pallida (∆Vac binding/Vac sensor above 1%) from other cyst nematodes (∆Vac binding/Vac sensor below 1%). It was confirmed that DNA either extracted with FTA-cards or Lab extraction Kit was of enough quantity and quality to detect G. pallida whenever present (alone or in mixed samples), ensuring probe specificity and sensitivity. This work provides insights for a new strategy to construct advanced devices for pathogens in-field diagnostics. LAMP runs separately but can be easily integrated into a single device.

A magnetic nanoparticle-based microfluidic device fabricated using a 3D-printed mould for separation of Escherichia coli from blood.

Herein, A microfluidic device is described, produced with a 3D-printed master mould that rapidly separates and concentrates Escherichia coli directly from whole blood samples, enabling a reduction in the turnaround time of bloodstream infections (BSIs) diagnosis. Moreover, it promotes the cleansing of the blood samples whose complexity frequently hampers bacterial detection. The device comprises a serpentine mixing channel with two inlets, one for blood samples (spiked with bacteria) and the other for magnetic nanoparticles (MNPs) functionalized with a (bacterio)phage receptor-binding protein (RBP) with high specificity for E. coli. After the magnetic labelling of bacteria throughout the serpentine, the microchannel ends with a trapping reservoir where bacteria-MNPs conjugates are concentrated using a permanent magnet. The optimized sample preparation device successfully recovered E. coli (on average, 66%) from tenfold diluted blood spiked within a wide range of bacterial load (102 CFU to 107 CFU mL-1). The non-specific trapping, tested with Staphylococcus aureus, was at a negligible level of 12%. The assay was performed in 30 min directly from diluted blood thus presenting an advantage over the conventional enrichment in blood cultures (BCs). The device is simple and cheap to fabricate and can be tailored for multiple bacterial separation from complex clinical samples by using RBPs targeting different species. Moreover, the possibility to integrate a biosensing element to detect bacteria on-site can provide a reliable, fast, and cost-effective point-of-care device.

Dependence of Sensitivity, Derivative of Transfer Curve and Current on Bias Voltage Magnitude and Polarity in Tunneling Magnetoresistance Sensors.

The sensitivity of tunneling magnetoresistance sensors is an important performance parameter. It depends on the derivative of resistance versus magnetic field (transfer curve) and the current and is expressed as the product of the two factors. Previous research has demonstrated that the bias voltage has a significant impact on the sensitivity. However, no research has been conducted into the dependence of current and the derivative on bias voltage magnitude and polarity, and their contribution to the sensitivity. Thus, this paper investigates the dependence of sensitivity, derivative of resistance versus magnetic field curve and current on bias voltage magnitude and polarity in CoFeB/MgO/CoFeB-based tunneling magnetoresistance sensors with weak, strong and no voltage-controlled perpendicular magnetic anisotropy modification. It demonstrates that the sensitivity dependence on bias voltage for sensors with voltage controlled magnetic anisotropy modification showed no saturation up to 1 V. Moreover, the sensitivity asymmetry with respect to bias polarity changed significantly with bias, reaching a ratio of 6.7. Importantly, the contribution of current and the derivative of resistance versus magnetic field curve to the sensitivity showed a crossover. The current dominated the bias dependence of sensitivity below the crossover voltage and the derivative above the voltage. Furthermore, the crossover voltage in sensors without voltage controlled magnetic anisotropy modification did not depend on polarity, whereas in sensors with voltage controlled magnetic anisotropy modification, it appeared at significantly higher voltage under positive than negative polarity.

A Lab-on-a-Chip Approach for the Detection of the Quarantine Potato Cyst Nematode Globodera pallida.

The potato cyst nematode (PCN), Globodera pallida, has acquired significant importance throughout Europe due to its widespread prevalence and negative effects on potato production. Thus, rapid and reliable diagnosis of PCN is critical during surveillance programs and for the implementation of control measures. The development of innovative technologies to overcome the limitations of current methodologies in achieving early detection is needed. Lab-on-a-chip devices can swiftly and accurately detect the presence of certain nucleotide sequences with high sensitivity and convert the presence of biological components into an understandable electrical signal by combining biosensors with microfluidics-based biochemical analysis. In this study, a specific DNA-probe sequence and PCR primers were designed to be used in a magnetoresistive biosensing platform to amplify the internal transcribed spacer region of the ribosomal DNA of G. pallida. Magnetic nanoparticles were used as the labelling agents of asymmetric PCR product through biotin−streptavidin interaction. Upon target hybridization to sensor immobilized oligo probes, the fringe field created by the magnetic nanoparticles produces a variation in the sensor's electrical resistance. The detection signal corresponds to the concentration of target molecules present in the sample. The results demonstrate the suitability of the magnetic biosensor to detect PCR target product and the specificity of the probe, which consistently distinguishes G. pallida (DV/V > 1%) from other cyst nematodes (DV/V < 1%), even when DNA mixtures were tested at different concentrations. This shows the magnetic biosensor's potential as a bioanalytical device for field applications and border phytosanitary inspections.

Non-invasive diagnosis and monitoring tool of children's mental health: A point-of-care immunosensor for IL-6 quantification in saliva samples.

Mental disorders are commonly featured as chronic conditions with often onset during childhood. In this context, inflammation has been associated with a higher risk of developing physical and mental health problems. Interleukin (IL)-6 is a key mediator of inflammatory responses and plays a pivotal role in immune and nervous system interaction. High levels of IL-6 during childhood are associated with mental problems, indicating that the IL-6 molecular pathway may represent a new target for monitoring and treating these conditions. Here, we report the detection of IL-6 in saliva samples from children (N = 118, mean age 4.4 years old) with behavioral problems using an immunosensor based on electrochemical impedance spectroscopy. This work demonstrates that the proposed immunosensor requires smaller sample volumes and is significantly faster and more sensitive than conventional ELISA while maintaining comparable levels of specificity and reproducibility. The point-of care immunosensor for detection of IL-6 in saliva samples presented herewith is, therefore, an attractive solution to the clinical practice as a rapid non-invasive, high-sensitive monitoring tool of mental health problems, especially in vulnerable patient populations such as children.

A Phage Receptor-Binding Protein as a Promising Tool for the Detection of Escherichia coli in Human Specimens.

Escherichia coli is a problematic pathogen that causes life-threatening diseases, being a frequent causative agent of several nosocomial infections such as urinary tract and bloodstream infections. Proper and rapid bacterial identification is critical for allowing prompt and targeted antimicrobial therapy. (Bacterio)phage receptor-binding proteins (RBPs) display high specificity for bacterial surface epitopes and, therefore, are particularly attractive as biorecognition elements, potentially conferring high sensitivity and specificity in bacterial detection. In this study, we elucidated, for the first time, the potential of a recombinant RBP (Gp17) to recognize E. coli at different viability states, such as viable but not culturable cells, which are not detected by conventional techniques. Moreover, by using a diagnostic method in which we combined magnetic and spectrofluorimetric approaches, we demonstrated the ability of Gp17 to specifically detect E. coli in various human specimens (e.g., whole blood, feces, urine, and saliva) in about 1.5 h, without requiring complex sample processing.

An integrated device for fast and sensitive immunosuppressant detection.

The present paper describes a compact point of care (POC) optical device for therapeutic drug monitoring (TDM). The core of the device is a disposable plastic chip where an immunoassay for the determination of immunosuppressants takes place. The chip is designed in order to have ten parallel microchannels allowing the simultaneous detection of more than one analyte with replicate measurements. The device is equipped with a microfluidic system, which provides sample mixing with the necessary chemicals and pumping samples, reagents and buffers into the measurement chip, and with integrated thin film amorphous silicon photodiodes for the fluorescence detection. Submicrometric fluorescent magnetic particles are used as support in the immunoassay in order to improve the efficiency of the assay. In particular, the magnetic feature is used to concentrate the antibody onto the sensing layer leading to a much faster implementation of the assay, while the fluorescent feature is used to increase the optical signal leading to a larger optical dynamic change and consequently a better sensitivity and a lower limit of detection. The design and development of the whole integrated optical device are here illustrated. In addition, detection of mycophenolic acid and cyclosporine A in spiked solutions and in microdialysate samples from patient blood with the implemented device are reported.

Room temperature two terminal tunnel magnetoresistance in a lateral graphene transistor.

We investigate the behavior of both pure spin and spin-polarized currents measured with four-probe non-local and two probe local configurations up to room temperature and under an external gate voltage in a lateral graphene transistor, produced using a standard large-scale microfabrication process. The high spin diffusion length of pristine graphene in the channel, measured both directly and by the Hanle effect, and the tuning of the relationship between the electrode resistance areas present in the device architecture allowed us to observe local tunnel magnetoresistance at room temperature, a new finding for this type of device. The results also indicate that while pure spin currents are less sensitive to temperature variations, spin-polarized current switching by an external voltage is more efficient, due to a combination of the Rashba effect and a change in carrier mobility by a Fermi level shift.

Faecal Diagnostic Biomarkers for Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. Cancer progression, including invasion and metastasis, is a major cause of death among CRC patients. Current methods for CRC screening commonly consist of a combination of faecal immunochemical test (FIT) for stool occult blood detection and invasive procedures such as colonoscopy. Considering the slow progression of CRC, and that symptoms usually emerge at advanced stages, its early diagnostic can limit cancer's spread and provide a successful treatment. Biomarkers have a high potential for the diagnosis of CRC in either blood or stool samples. METHODS: In this study, we analysed the diagnostic value of six different biomarkers in stool samples of patients with CRC, advanced adenomas, other lesions and healthy individuals. We have also assessed the overall performance of the combination of these biomarkers for CRC detection. RESULTS: The results indicate that haemoglobin (Hb) and M2-pyruvate kinase (M2-PK) levels were increased in CRC patients in comparison to the controls. Conversely, the concentrations of matrix metalloproteinase (MMP)-2, MMP-9, and tumour necrosis factor-alpha (TNF-α) were not significantly different between the tested groups. CONCLUSION: The combination of FIT-Hb with the M2-PK levels increased the specificity or sensitivity for CRC detection and thus present potential as faecal diagnostic biomarkers for CRC.

Non-volatile artificial synapse based on a vortex nano-oscillator.

In this work, a new mechanism to combine a non-volatile behaviour with the spin diode detection of a vortex-based spin torque nano-oscillator (STVO) is presented. Experimentally, it is observed that the spin diode response of the oscillator depends on the vortex chirality. Consequently, fixing the frequency of the incoming signal and switching the vortex chirality results in a different rectified voltage. In this way, the chirality can be deterministically controlled via the application of electrical signals injected locally in the device, resulting in a non-volatile control of the output voltage for a given input frequency. Micromagnetic simulations corroborate the experimental results and show the main contribution of the Oersted field created by the input RF current density in defining two distinct spin diode detections for different chiralities. By using two non-identical STVOs, we show how these devices can be used as programmable non-volatile synapses in artificial neural networks.

Rapid and multiplex detection of nosocomial pathogens on a phage-based magnetoresistive lab-on-chip platform.

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.

Bias Voltage Dependence of Sensing Characteristics in Tunneling Magnetoresistance Sensors.

One of the characteristic features of tunneling magnetoresistance (TMR) sensors is a strong influence of bias voltage on tunneling current. Since fundamental sensing characteristics of the sensors are primarily determined by the tunneling current, the bias voltage should impact these characteristics. Previous research has indeed showed the influence of the bias voltage on the magnetic field detection and sensitivity. However, the effect has not been investigated for nonlinearity and hysteresis and the influence of bias voltage polarity has not yet been addressed. Therefore, this paper systematically investigates the dependence of field sensitivity, nonlinearity, hysteresis and magnetic field detection of CoFeB/MgO/CoFeB-based magnetoresistance sensors on bias voltage magnitude and polarity. The sensitivity and field detection of all sensors improved significantly with the bias, whereas the nonlinearity and hysteresis deteriorated. The sensitivity increased considerably (up to 32 times) and linearly with bias up to 0.6 V. The field detection also decreased substantially (up 3.9 times) with bias and exhibited the minimum values for the same magnitude under both polarities. Significant and linear increases with bias were also observed for nonlinearity (up to 26 times) and hysteresis (up to 33 times). Moreover, not only the voltage magnitude but also the polarity had a significant effect on the sensing characteristics. This significant, linear and simultaneous effect of improvement and deterioration of the sensing characteristics with bias indicates that both bias voltage magnitude and polarity are key factors in the control and modification of these characteristics.

Two-dimensional arrays of vertically packed spin-valves with picoTesla sensitivity at room temperature.

A new device architecture using giant magnetoresistive sensors demonstrates the capability to detect very low magnetic fields on the pT range. A combination of vertically packed spin-valve sensors with two-dimensional in-plane arrays, connected in series and in parallel, delivers a final detection level of 360 pT/[Formula: see text] at 10 Hz at room temperature. The device design is supported by an analytical model developed for a vertically packed spin-valve system, which takes into account all magnetic couplings present. Optimization concerning the spacer thickness and sensor physical dimensions depending on the number of pilled up spin-valves is necessary. To push the limits of detection, arrays of a large number of sensing elements (up to 440,000) are patterned with a geometry that improves sensitivity and in a configuration that reduces the resistance, leading to a lower noise level. The final device performance with pT detectivity is demonstrated in an un-shielded environment suitable for detection of bio-signals.

Phenotypic Analysis of Urothelial Exfoliated Cells in Bladder Cancer via Microfluidic Immunoassays: Sialyl-Tn as a Novel Biomarker in Liquid Biopsies.

Bladder cancer is the most common malignancy of the urinary tract, having one of the highest recurrence rates and progression from non-muscle to muscle invasive bladder cancer that commonly leads to metastasis. Cystoscopy and urine cytology are the standard procedures for its detection but have limited clinical sensitivity and specificity. Herein, a microfluidic device, the UriChip, was developed for the enrichment of urothelial exfoliated cells from fresh and frozen urine, based on deformability and size, and the cancer-associated glycan Sialyl-Tn explored as a putative bladder cancer urinary biomarker. Spiking experiments with bladder cancer cell lines showed an isolation efficiency of 53%, while clinical sample analyses revealed retention of cells with various morphologies and sizes. in situ immunoassays demonstrated significantly higher number of Sialyl-Tn-positive cells in fresh and frozen voided urine from bladder cancer patients, compared to healthy individuals. Of note, urothelial exfoliated cells from cryopreserved urine sediments were also successfully isolated by the UriChip, and found to express significantly high levels of Sialyl-Tn. Remarkably, Sialyl-Tn expression is correlated with tumor stage and grade. Overall, our findings demonstrate the potential of UriChip and Sialyl-Tn to detect urothelial bladder cancer cells in follow-up and long-term retrospective studies.

Spintronic Sensors Based on Magnetic Tunnel Junctions for Wireless Eye Movement Gesture Control.

The tracking of eye gesture movements using wearable technologies can undoubtedly improve quality of life for people with mobility and physical impairments by using spintronic sensors based on the tunnel magnetoresistance (TMR) effect in a human-machine interface. Our design involves integrating three TMR sensors on an eyeglass frame for detecting relative movement between the sensor and tiny magnets embedded in an in-house fabricated contact lens. Using TMR sensors with the sensitivity of 11 mV/V/Oe and ten <1 mm3 embedded magnets within a lens, an eye gesture system was implemented with a sampling frequency of up to 28 Hz. Three discrete eye movements were successfully classified when a participant looked up, right or left using a threshold-based classifier. Moreover, our proof-of-concept real-time interaction system was tested on 13 participants, who played a simplified Tetris game using their eye movements. Our results show that all participants were successful in completing the game with an average accuracy of 90.8%.

Point-of-care quantification of serum cellular fibronectin levels for stratification of ischemic stroke patients.

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.

Digital and analogue modulation and demodulation scheme using vortex-based spin torque nano-oscillators.

In conventional communications systems, information is transmitted by modulating the frequency, amplitude or phase of the carrier signal, which often occurs in a binary fashion over a very narrow bandwidth. Recently, ultra-wideband signal transmission has gained interest for local communications in technologies such as autonomous local sensor networks and on-chip communications, which presents a challenge for conventional electronics. Spin-torque nano-oscillators (STNOs) have been studied as a potentially low power highly tunable frequency source, and in this report we expand on this to show how a specific dynamic phase present in vortex-based STNOs makes them also well suited as Wideband Analogue Dynamic Sensors (WADS). This multi-functionality of the STNOs is the basis of a new modulation and demodulation scheme, where nominally identical devices can be used to transmit information in both a digital or analogue manner, with the potential to allow the highly efficient transmittance of data.

Non-invasive molecular assessment of human embryo development and implantation potential.

In vitro fertilization (IVF) is the most common assisted reproductive technology used to treat infertility. Embryo selection for transfer in IVF cycles relies on the morphological evaluation by embryologists, either by conventional microscopic assessment or more recently by time-lapse imaging systems. Despite the introduction of time-lapse imaging improvements in IVF success rates have failed to materialize, therefore alternative approaches are needed. Recent studies have shown that embryos resulting in successful pregnancy differ in their secretome and metabolism compared to embryos that fail to implant, suggesting that molecular analysis of embryo culture medium could assist in non-invasive single embryo selection. However, this approach has yet to be adopted clinically due to the lack of appropriate highly sensitive screening technologies needed to assess volume-limited samples. Here we report the detection of hCGß, IL-8 and TNFα from conditioned culture media of single human embryos using electrochemical impedance spectroscopy. The impedimetric immunosensors revealed that morphologically non-viable embryos produce higher levels of IL-8 and TNFα, associated with abnormal cell division and cell death, respectively. More importantly, hCGß detection was able to discriminate apparently morphologically identical viable embryos. This work brings an objective dimension to embryo selection, which could overcome the major limitations of morphology-based embryo selection for implantation. Future work should include the validation of these biomarkers in a large patient cohort.

Nanoscale true random bit generator based on magnetic state transitions in magnetic tunnel junctions.

We present an investigation into the in-plane field induced free layer state transitions found in magnetic tunnel junctions. By applying an ac current into an integrated field antenna, the magnetisation of the free layer can be switched between the magnetic vortex state and the quasi-uniform anti-parallel state. When in the magnetic vortex state, the vortex core gyrates a discrete number of times, and at certain frequencies there is a 50% chance of the core gyrating n or n - 1 times, leading to the proposal of a novel nanoscale continuous digital true random bit generator.

Manipulation of Magnetic Beads with Thin Film Microelectromagnet Traps.

Integration of point-of-care assays can be facilitated with the use of actuated magnetic beads (MB) to perform testing in less expensive settings to enable the delivery of cost-effective care. In this paper we present six different designs of planar microelectromagnets traps (MEMT) with four external coils in series and one central coil connected for an opposite direction of manipulation of MB in microfluidic flows. The development of a simulation tool facilitated the rapid and efficient optimization of designs by presenting the influence of system variables on real time concentrations of MB. Real time experiments are in good agreement with the simulations and showed that the design enabled synchronous concentration and dispersion of MB on the same MEMT. The yield of local concentration is seen to be highly dependent on coil design. Additional coil turns between the central and external coils (inter-windings) doubled magnetic concentration and repulsion with no significant electrical resistance increase. The assemblage of a copper microchannel closed loop cooling system to the coils successfully eliminated the thermal drift promoted by joule heating generated by applied current.