Biominerals and Bioinspired Materials in Biosensing: Recent Advancements and Applications.

Inspired by nature's remarkable ability to form intricate minerals, researchers have unlocked transformative strategies for creating next-generation biosensors with exceptional sensitivity, selectivity, and biocompatibility. By mimicking how organisms orchestrate mineral growth, biomimetic and bioinspired materials are significantly impacting biosensor design. Engineered bioinspired materials offer distinct advantages over their natural counterparts, boasting superior tunability, precise controllability, and the ability to integrate specific functionalities for enhanced sensing capabilities. This remarkable versatility enables the construction of various biosensing platforms, including optical sensors, electrochemical sensors, magnetic biosensors, and nucleic acid detection platforms, for diverse applications. Additionally, bioinspired materials facilitate the development of smartphone-assisted biosensing platforms, offering user-friendly and portable diagnostic tools for point-of-care applications. This review comprehensively explores the utilization of naturally occurring and engineered biominerals and materials for diverse biosensing applications. We highlight the fabrication and design strategies that tailor their functionalities to address specific biosensing needs. This in-depth exploration underscores the transformative potential of biominerals and materials in revolutionizing biosensing, paving the way for advancements in healthcare, environmental monitoring, and other critical fields.

Biological sensing using anomalous hall effect devices.

This paper outlines an approach to biological sensing involving the use of spintronic devices to sense magnetic particles attached to biological carriers. We developed an enzyme-linked immunosorbent assay (ELISA)-based Anomalous Hall Effect magnetic sensor via surface functionalization using Triethoxysilylundecanal (TESUD). The proposed sensor uses a CoFeB/MgO heterostructure with a perpendicular magnetic anisotropy. Through several sets of magnetic layer thickness, this work also explored the optimization process of ferromagnetic layer used. Our spintronics-based biosensor is compatible with semiconductor fabrication technology and can be effectively miniaturized to integrate with semiconductor chips, which has the advantage of reduced manufacturing cost and reduced power consumption. The proposed sensor provides real-time measurement results and it is competitive to conventional biological colorimetric measurement systems in terms of accuracy and immediacy.

Resonance light scattering aptasensor for urinary 8-hydroxy-2'-deoxyguanosine based on magnetic nanoparticles: a preliminary study of oxidative stress association with air pollution.

An aptamer based method is described for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) using resonance light scattering (RLS). Magnetic nanoparticles (MNPs) were employed as RLS probes. The probe DNA was placed on the surface of MNPs, which produces a rather low RLS signal. If, however, probe DNA hybridizes with the aptamer against 8-OHdG, a sandwich structure will be formed. This results in a significant enhancement of RLS intensity. The aptamer was used as the recognition element to capture 8-OHdG. 8-OHdG has a stronger affinity for the aptamer than probe DNA, and the conformation of the aptamer therefore switches from a double-stranded to a G-quadruplex structure. As a result, MNPs labeled with probe DNA are released, and RLS intensity decreases. The method allows 8-OHdG to be detected with a linear response in the 32 pM - 12.0 nM concentration range and an 11 pM limit of detection (at 3.29SB/m, according to the recent recommendation of IUPAC). The MNPs can be reused 5 times by applying an external magnetic field for collection. The method was successfully applied to analyze human urine samples for its content of 8-OHdG. It was also found that the levels of 8-OHdG noticeably increased with the increase of the Air Quality Index. Conceivably, the method is a viable tool to investigate the relationship between 8-OHdG levels and the effect of air pollution. Graphical abstract A reusable sensing strategy was constructed to detect urinary 8-OHdG based on "turn-off" resonance light scattering. The LOD was as low as 11 pM. This study showed some preliminary data for the association between oxidative stress and air pollution.

Contactless Measurement of Magnetic Nanoparticles on Lateral Flow Strips Using Tunneling Magnetoresistance (TMR) Sensors in Differential Configuration.

Magnetic nanoparticles (MNPs) are commonly used in biomedical detection due to their capability to bind with some specific antibodies. Quantification of biological entities could be realized by measuring the magnetic response of MNPs after the binding process. This paper presents a contactless scanning prototype based on tunneling magnetoresistance (TMR) sensors for quantification of MNPs present in lateral flow strips (LFSs). The sensing unit of the prototype composes of two active TMR elements, which are parallel and closely arranged to form a differential sensing configuration in a perpendicular magnetic field. Geometrical parameters of the configuration are optimized according to theoretical analysis of the stray magnetic field produced by the test line (T-line) while strips being scanned. A brief description of our prototype and the sample preparation is presented. Experimental results show that the prototype exhibits the performance of high sensitivity and strong anti-interference ability. Meanwhile, the detection speed has been improved compared with existing similar techniques. The proposed prototype demonstrates a good sensitivity for detecting samples containing human chorionic gonadotropin (hCG) at a concentration of 25 mIU/mL. The T-line produced by the sample with low concentration is almost beyond the visual limit and produces a maximum stray magnetic field some 0.247 mOe at the sensor in the x direction.

A 256 pixel magnetoresistive biosensor microarray in 0.18µm CMOS.

Magnetic nanotechnologies have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors coupled with magnetic nanotags (MNTs) possess great promise as ultra-sensitive biosensors for diagnostics. We report an integrated sensor interface for an array of 256 GMR SV biosensors designed in 0.18 µm CMOS. Arranged like an imager, each of the 16 column level readout channels contains an analog front- end and a compact ΣΔ modulator (0.054 mm2) with 84 dB of dynamic range and an input referred noise of 49 nT/√Hz. Performance is demonstrated through detection of an ovarian cancer biomarker, secretory leukocyte peptidase inhibitor (SLPI), spiked at concentrations as low as 10 fM. This system is designed as a replacement for optical protein microarrays while also providing real-time kinetics monitoring.

Cluster-bomb type magnetic biosensor for ultrasensitive detection of Vibrio parahaemolyticus based on low field nuclear magnetic resonance.

Herein, a novel cluster-bomb type signal sensing and amplification strategy in low field nuclear magnetic resonance was proposed, and a magnetic biosensor for ultrasensitive homogeneous immunoassay of Vibrio parahaemolyticus (VP) was developed. The capture unit MGO@Ab was magnetic graphene oxide (MGO) immobilized by VP antibody (Ab) to capture VP. And, the signal unit PS@Gd-CQDs@Ab was polystyrene (PS) pellets covered by Ab to recognize VP and Gd-CQDs i.e. carbon quantum dots (CQDs) containing lots of magnetic signal labels Gd3+. In presence of VP, the immunocomplex signal unit-VP-capture unit could be formed and separated by magnetic force conveniently from the sample matrix. With the successive introduction of disulfide threitol and hydrochloric acid, signal units were cleaved and disintegrated, resulting in a homogeneous dispersion of Gd3+. Thus, cluster-bomb type dual signal amplification was achieved through increasing the amount and the dispersity of signal labels simultaneously. Under optimal experimental conditions, VP could be detected in the concentration range of 5-1.0 × 106 CFU/mL, with a limit of quantitation (LOQ) 4 CFU/mL. In addition, satisfactory selectivity, stability and reliability could be obtained. Therefore, this cluster-bomb type signal sensing and amplification strategy is powerful in designing magnetic biosensor and detecting pathogenic bacteria.

An aptamer-based magnetic flow cytometer using matched filtering.

Facing unprecedented population-ageing, the management of noncommunicable diseases (NCDs) urgently needs a point-of-care (PoC) testing infrastructure. Magnetic flow cytometers are one such solution for rapid cancer cellular detection in a PoC setting. In this work, we report a giant magnetoresistive spin-valve (GMR SV) biosensor array with a multi-stripe sensor geometry and matched filtering to improve detection accuracy without compromising throughput. The carefully designed sensor geometry generates a characteristic signature when cells labeled with magnetic nanoparticles (MNPs) pass by thus enabling multi-parametric measurement like optical flow cytometers (FCMs). Enumeration and multi-parametric information were successfully measured across two decades of throughput (37 - 2730 cells/min). 10-µm polymer microspheres were used as a biomimetic model where MNPs and MNP-decorated polymer conjugates were flown over the GMR SV sensor array and detected with a signal-to-noise ratio (SNR) as low as 2.5 dB due to the processing gain afforded by the matched filtering. The performance was compared against optical observation, exhibiting a 92% detection efficiency. The system achieved a 95% counting accuracy for biomimetic models and 98% for aptamer-based pancreatic cancer cell detection. This system demonstrates the ability to perform reliable flow cytometry toward PoC diagnostics to benefit NCD control plans.

Assay of miRNA in cell samples using enhanced resonance light scattering technique based on self aggregation of magnetic nanoparticles.

AIMS: miRNAs are regarded as potential biomarkers correlated with the development and progression of many diseases. However, it is a challenge to construct a sensitive method to detect them without using time-consuming radioactive labeling or complex amplification strategies. METHODS: A facile resonance light scattering (RLS) system was developed for the detection of miRNA employing magnetic nanoparticles (MNPs) as RLS probes. MNPs were coated with streptavidin. DNA probes were modified on the surface of MNPs based on the specific interaction of streptavidin and biotin forming MNPs@DNA probes. MNPs@DNA probes dispersed in homogeneous media causing low RLS signal. RESULTS & CONCLUSION: miRNA hybridized with DNA probes resulting in the aggregation of MNPs and inducing the enhancement of RLS intensity. miRNAs were determined successfully with limit of detection at 0.9 picomole per liter (pM). The potential clinical application of the present biosensor was also demonstrated by measuring miRNAs in human normal and cancer cells, and human serum samples.

Modelling of magnetoimpedance response of thin film sensitive element in the presence of ferrogel: Next step toward development of biosensor for in-tissue embedded magnetic nanoparticles detection.

In-tissue embedded magnetic nanoparticle (MNPs) detection is one of the most interesting cases for cancer research. In order to understand the origin, the limits and the way of improvement of magnetic biosensor sensitivity for the detection of 3D mezoscopic distributions of MNPs, we have developed a magnetoimpedance biosensor prototype with a [Cu (3 nm)/FeNi(100 nm)]5/Cu(500 nm)/[FeNi(100 nm)/Cu(3 nm)]5 rectangular sensitive element. Magnetoimpedance (MI) responses were measured with and without polyacrylamide ferrogel layer mimicking natural tissue in order to evaluate stray fields of embedded MNPs of γ-Fe2O3 iron oxide. A model for MI response based on a solution of Maxwell equations with Landau-Lifshitz equation was developed in order to understand the origin of the prototype sensitivity which reached 1.3% of ΔZ/Z per 1% of MNPs concentration by weight. To make this promising technique useful for magnetically labeled tissue detection, a synthesis of composite gels with MNPs agglomerates compactly located inside pure gel and their MI testing are still necessary.

Denaturation strategies for detection of double stranded PCR products on GMR magnetic biosensor array.

Microarrays and other surface-based nucleic acid detection schemes rely on the hybridization of the target to surface-bound detection probes. We present the first comparison of two strategies to detect DNA using a giant magnetoresistive (GMR) biosensor platform starting from an initially double-stranded DNA target. The target strand of interest is biotinylated and detected by the GMR sensor by linking streptavidin magnetic nanoparticles (MNPs) to the sensor surface. The sensor platform has a dynamic detection range from 40pM to 40nM with highly reproducible results and is used to monitor real-time binding signals. The first strategy, using off-chip heat denaturation followed by sequential on-chip incubation of the nucleic acids and MNPs, produces a signal that stabilizes quickly but the signal magnitude is reduced due to competitive rehybridization of the target in solution. The second strategy, using magnetic capture of the double-stranded product followed by denaturing, produces a higher signal but the signal increase is limited by diffusion of the MNPs. Our results show that both strategies give highly reproducible results but that the signal obtained using magnetic capture is higher and insensitive to rehybridization.

Giant magnetoresistive-based biosensing probe station system for multiplex protein assays.

In this study, a sensitive immune-biosensing system capable of multiplexed, real-time electrical readout was developed based on giant magnetoresistive (GMR) sensor array to detect a panel of protein biomarkers simultaneously. PAPP-A, PCSK9, and ST2 have been regarded as promising candidate biomarkers for cardiovascular diseases. Early detection of multiple biomarkers for a disease could enable accurate prediction of a disease risk. 64 nano-size GMR sensors were assembled onto one 16 mm × 16 mm chip with a reaction well, and they could work independently and be monitored simultaneously. A detect limit of 40 pg/mL for ST2 antigen had been achieved, and the dynamic ranges for the three proteins detection were up to four orders of magnitude. The GMR sensing platform was also selective enough to be directly used in serum samples. In addition, a lab-based probe station has been designed to implement quick lab-on-a-chip experiments instead of wire bonding. It has a potential application in clinical biomarkers identification and screening, and can be extended to fit other biosensing schemes.

An efficient biosensor made of an electromagnetic trap and a magneto-resistive sensor.

Magneto-resistive biosensors have been found to be useful because of their high sensitivity, low cost, small size, and direct electrical output. They use super-paramagnetic beads to label a biological target and detect it via sensing the stray field. In this paper, we report a new setup for magnetic biosensors, replacing the conventional "sandwich" concept with an electromagnetic trap. We demonstrate the capability of the biosensor in the detection of E. coli. The trap is formed by a current-carrying microwire that attracts the magnetic beads into a sensing space on top of a tunnel magneto-resistive sensor. The sensor signal depends on the number of beads in the sensing space, which depends on the size of the beads. This enables the detection of biological targets, because such targets increase the volume of the beads. Experiments were carried out with a 6 µm wide microwire, which attracted the magnetic beads from a distance of 60 µm, when a current of 30 mA was applied. A sensing space of 30 µm in length and 6 µm in width was defined by the magnetic sensor. The results showed that individual E. coli bacterium inside the sensing space could be detected using super-paramagnetic beads that are 2.8 µm in diameter. The electromagnetic trap setup greatly simplifies the device and reduces the detection process to two steps: (i) mixing the bacteria with magnetic beads and (ii) applying the sample solution to the sensor for measurement, which can be accomplished within about 30 min with a sample volume in the µl range. This setup also ensures that the biosensor can be cleaned easily and re-used immediately. The presented setup is readily integrated on chips via standard microfabrication techniques.