Magnetoelastic Biosensor Research Articles

Novel flexible magnetoelastic biosensor based on PDMS/FeSiB/QD composite film for the detection of African swine fever virus P72 protein.

African swine fever (ASF) is a highly contagious and severe hemorrhagic disease caused by the African swine fever virus (ASFV). The continuous spread of ASFV affects the safety of the global meat supply; therefore, the establishment of sensitive and specific detection methods for ASFV has become an important hot spot in food safety. Herein, we developed a flexible magnetoelastic (ME) biosensor based on PDMS/FeSiB/QDs composite films for the detection of ASFV P72 protein. Based on the high luminescence performance of CsPbBr3 quantum dots and the excellent magnetoelastic effect of FeSiB, flexible ME biosensors convert stress signals generated by antibody-antigen-specific binding into optical and electromagnetic signals. The nanostructures covalently linked by quantum dots and PDMS provide biomodification sites for ASFV P72 antibodies, simplifying the functionalization modification process compared to the case of conventional biosensors. The deformation of the PDMS film is amplified, and the conversion of surface stress signals to electrical signals is enhanced by exposing the biosensor to a uniform magnetic field. The experimental results proved that the flexible ME biosensor has a wide linear range of 10 ng mL-1-100 μg mL-1, and the detection limit is as low as 0.079 ng mL-1. Moreover, the flexible ME biosensor also shows good stability, sensitivity and specificity, confirming the potential for early disease screening.

A novel magnetoelastic biosensor consisting of carbon quantum dots/nitrocellulose membranes and NiFe2O4/ polylactic acid based on 3D printing for α2-macroglobulin detection

α2-macroglobulin (α2-M) have crucial clinical significance as a potent biomarker for diabetes nephropathy (DN). There is an increasing demand for rapid detection of α2-M. Herein, a magnetoelastic (ME) biosensor with a layered composite structure is developed for α2-M detection. Based on 3D printing, the basal layer of the biosensor is prepared as a grid structure fabricated by polylactic acid (PLA) doped with NiFe2O4. The conductivity of the biosensor was improved significantly due to the addition of multi-walled carbon nanotubes (MWCNTs). The biological site for capturing α2-M antigen was provided by the carbon quantum dots (CDs) coupled with anti-α-2M (anti-α2-M@CDs) in the nitrocellulose filter (NC) membrane. Meanwhile, the distribution of antibodies on the biosensor surface can be observed more directly due to the fluorescence characteristics of CDs. The biosensor in this work can realize multi-pattern recognition of fluorescent signal and electromagnetic signal. The results show that the limit of detection (LOD) was 0.506 ng/mL in the linear range from 10 ng/mL to 100 µg/mL and the linear equation of fitting curve is: y = 0.21 x - 0.15. The ME biosensors with a simple preparation method have advantages of high sensitivity, good stability and low LOD, showing the great potential for α2-M detection.

A novel flexible magnetoelastic biosensor with “sandwich” structure based on transferrin encapsulated gold nanoclusters for 5-hydroxytryptamine detection

5-hydroxytryptamine (5-HT), a mono-amine neurotransmitter, plays an important role in regulating the dynamics of neural circuits in the central nervous system and enteric nervous system. Accurate and sensitive monitoring of 5-HT will provide critical information for diagnosing many psychiatric and neurological disorders. However, there are no superior clinical assays for the detection of 5-HT, and existing methods of gas chromatographs and mass spectrometers are expensive, limiting portable and real-time monitoring as diagnostic approaches in the clinical setting. Therefore, a convenient, rapid, and low-cost method for the detection of 5-HT is still in demand in current clinical medicine. Herein, a novel flexible magnetoelastic (ME) biosensor with “sandwich” structure is proposed for 5-HT detection based on transferrin encapsulated gold nanoclusters (Tf-AuNCs). Combined with the magnetoelastic effect of CoFe2O4, the excellent conductivity of silver nanowires (AgNWs), and the fluorescence properties of Tf-AuNCs, the ME biosensor designed in this paper can achieve multi-signal recognition. Rapid and sensitive detection of 5-HT is achieved by a biosensing process that converts surface stress signal into magnetoelectric signals. The biosensor is capable of detecting 5-HT with different concentrations in a linear range of 10 ng/mL-100 μg/mL (R2 = 0.97119) with a lower detection limit (LOD) of 0.33 ng/mL. The accurate measurement results of 5-HT in human serum of clinical samples demonstrated the feasibility of the biosensor for 5-HT detection. This flexible ME biosensor was prepared in a simple process with great specificity and stability, providing a portable analytical device for the rapid and sensitive detection of 5-HT, which is of great significance for the clinical research of various neurological diseases.

Diagnosis, Bacterial Density, Food, and Agricultural Applications of Magnetoelastic Biosensors: Theory, Instrumentation, and Progress

Diagnosis, Bacterial Density, Food, and Agricultural Applications of Magnetoelastic Biosensors: Theory, Instrumentation, and Progress

Scorpion-Inspired, Hydrophobic, Highly Sensitive, and Paper-Based Magnetoelastic Biosensor for C-Reactive Protein Detection

Scorpion-Inspired, Hydrophobic, Highly Sensitive, and Paper-Based Magnetoelastic Biosensor for C-Reactive Protein Detection

Role of extrinsic factors on magnetoelastic resonance biosensors sensitivity

Magnetoelastic (ME) resonance devices are attractive for application as biosensors in health-related areas as they allow contactless detection of pathogenic agents with high sensitivity. After functionalization, they offer valuable diagnostic options that promote efficient capture of mass on the sensor surface through biological interactions. ME sensors are also sensitive to external factors such as temperature, magnetic fields, and variations in mass that can arise from processes unrelated to biological interactions, including corrosion and salt crystallization. This article evaluates extrinsic factors that affect the response of ME resonance sensors for diagnostic applications. In particular, the influence of heat treatments, operation temperature, applied DC magnetic field bias, and corrosive environment were studied. The control of all these factors is crucial for the design, fabrication, and functionalization of ME resonance biosensors and for the development of measuring instrumentation and effective measurement protocols. This work established maximum operating temperature and bias field variations to keep the sensor sensitivity. Heat treatment of the sensors before and after coating improved the signal-to-noise ratio and corrosion resistance. Further improvement in corrosion resistance was provided by cathodic protection, which has been proven beneficial for applications of ME resonance sensors in aqueous fluids.

Three-Dimensional Printed Flexible Magnetoelastic Biosensor for C-Reactive Protein Detection Based on Patterned PDMS/MnFe2O4 Film

Three-Dimensional Printed Flexible Magnetoelastic Biosensor for C-Reactive Protein Detection Based on Patterned PDMS/MnFe₂O₄ Film

User-friendly, signal-enhanced planar spiral coil-based magnetoelastic biosensor combined with humidity-resistant phages for simultaneous detection of Salmonella Typhimurium and Escherichia coli O157:H7 on fresh produce

A user-friendly, signal-enhanced magnetoelastic (ME) biosensor was newly constructed, consisting of three sensors, a movable pencil-type planar spiral coil, and a set of hand-held signal amplifiers. It was combined with humidity-resistant, wild-type phages instead of humidity-susceptible E2 phage to simultaneously detect Salmonella Typhimurium (ST) and Escherichia coli O157:H7 (EC) on the surface of an apple. The set of hand-held signal amplifiers, four times smaller than those in the planar spiral coil-based ME biosensor, was constructed with an optimal DC magnetic field strength of 76 G. These optimized hand-held signal amplifiers enhanced the signal amplitude of the sensor by up to 1.5 times, enabling the distinction of individual peaks from three sensors. Both phage-immobilized sensors detected each target specifically under ambient humidity without the need for a bulky humidifier. The optimized exposure time for phage binding with each target on fresh produce was 16 min, almost twice as fast as the rectangular solenoid coil-based ME biosensor. The signal-enhanced ME biosensor detected its target bacteria from a mixture of ST and EC inoculated on an apple simultaneously with an enhanced detection limit of 1.7 ± 0.4 log CFU/25 mm2 for ST and 1.6 ± 0.3 log CFU/25 mm2 for EC. Notably, the detection limit and sensitivity did not show significant differences between each single analyte and bacterial mixture, indicating no interference with another coexisting pathogens. Our findings highlight the signal-enhanced ME biosensor as a rapid, efficient, specific, and user-friendly method for the simultaneous detection of fresh produce-borne pathogens.

Performance of wild, tailed, humidity-robust phage on a surface-scanning magnetoelastic biosensor for Salmonella Typhimurium detection

A wild, tailed phage (TST) was compared with a genetically modified, filamentous phage (FST) for S. Typhimurium (ST) detection. When both phages were introduced into oppositely charged MUA and MUAM sensors, the RU values of TST showed an obvious increase on the MUAM sensor. The sensitivity of TST [54.78 ΔRU/(log PFU/mL)] was greater than that of FST [48.05 ΔRU/(log PFU/mL)]. The binding affinity (KD = 1.75 × 10−13 M) of TST on MUAM sensor was greater than that of FST. Both phages were specific to only ST, and TST exhibited a persistent binding capability at 50 % RH. When each phage-immobilized sensor was employed on chili pepper, the sensitivity [880.80 Hz/(log CFU/mL)] and detection limit (1.31 ± 0.27 log CFU/mL) of TST were significantly greater than those of FST. The orientation of TST on sensor promoted the uniform capture of bacteria and enhanced the reliable performance of a surface-scanning magnetoelastic biosensor.

Portable, High-Sensitive, and Metglas Alloy 2826 MB-Based Magnetoelastic Biosensor to Detect the Osteoarthritis Marker MMP-3

Osteoarthritis (OA) is one of the most common joint disorders affecting human health. Early detection of OA is essential for effective treatment of the disease. There is a growing demand of techniques for highly sensitive detection of trace OA markers. Here, the magnetoelastic (ME) biosensor based on Metglas alloy 2826 MB is presented to detect matrix metalloproteinase-3 (MMP-3) of the OA biomarker, through the measurement of resonant frequency changes with excellent magnetostrictive effects. The detection system consists of an ME chip immobilized with MMP-3 antibody and an electromagnetic coil. Since the ME biosensor is ultrasensitive to mass changes, the frequency shift caused by mass changes induced by antibody–antigen-specific binding can be used to reflect the amount of MMP-3. The ME biosensor has been applied to detect the actual joint fluid sample of OA patients, demonstrating its feasibility. The results show that this assay has a linear response to the MMP-3 concentrations ranging from 30.7 to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$2000\,\,{\mathrm {ng}} \cdot\,{\mathrm {mL}}^{-}1$ </tex-math></inline-formula> with a detection limit of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$30.7\,\,{\mathrm {ng}} \cdot\,{\mathrm {mL}}^{-}1$ </tex-math></inline-formula> , covering the range of clinical tests required for the diagnosis of OA. The ME biosensor provides a novel and viable method for the diagnosis of early OA.

A Novel Magnetoelastic Biosensor With Flexible TbDyFe Film as Sensing Materials for Osteoarthritis Marker MMP-3 Detection

A new design of flexible magnetoelastic (ME) biosensor based on TbDyFe/polystyrene-poly (ethylene-butylene)-polystyrene block copolymer (SEBS) film for the osteoarthritis (OA) marker matrix metalloproteinase 3 (MMP-3) detection is presented. This article studied a novel flexible ME film to replace the traditional rigid substrate for biosensors. The magnetostrictive material of TbDyFe was mixed homogeneously with paraffin solution to fabricate TbDyFe fluid, which was reacted at high temperature with SEBS in a certain ratio to prepare the film. TbDyFe/SEBS films were used as substrates for the immobilization of MMP-3 antibodies. Specific binding of antibodies to MMP-3 antigens generated compressive stress on the substrate surface, which in turn led to changes in magnetic permeability and impedance. To improve the sensitivity of the biosensor, the TbDyFe doping concentration was optimized and the magnetic response performance of the TbDyFe/SEBS composite film was measured. The results show that this assay is capable of detecting concentrations of MMP-3 between 0.76 and 10000 ng <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\cdot $ </tex-math></inline-formula> mL−1 with a detection limit of 0.76 ng <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\cdot $ </tex-math></inline-formula> mL−1, covering the range of clinical tests required for the diagnosis of OA. This novel flexible ME biosensor provides a viable method for the diagnosis and monitoring of OA.

Surface Functionalization, Bioanalysis, and Applications: Progress of New Magnetoelastic Biosensors

Surface Functionalization, Bioanalysis, and Applications: Progress of New Magnetoelastic Biosensors

Surface Functionalization, Bioanalysis, and Applications: Progress of New Magnetoelastic Biosensors

Magnetoelastic (ME) biosensors are portable, nontoxic, inexpensive, compatible with wireless networks, and have high sensitivity, accuracy, and specificity toward the target element. Thus, they have attracted considerable attention in application of biological identification, chemical detection, and medical diagnosis, as well as in many academic achievements in the field of sensor research. Herein, the recent progress of ME biosensors, including surface functionalization, bioanalysis, and its applications is critically reviewed. The remaining scientific and technological challenges related to the development of novel ME biosensors with new materials and structures in this field are elaborated, too. This review not only can provide a guideline for researchers in future development of ME biosensors, but also further improves their detection performance and expand the scope of their applications.

A Novel NiFe2O4/Paper-Based Magnetoelastic Biosensor to Detect Human Serum Albumin.

For the first time, a novel NiFe2O4/paper-based magnetoelastic (ME) biosensor was developed for rapid, sensitive, and portable detection of human serum albumin (HSA). Due to the uniquely magnetoelastic effect of NiFe2O4 nanoparticles and the excellent mechanical properties of the paper, the paper-based ME biosensor transforms the surface stress signal induced by the specific binding of HSA and antibody modified on the paper into the electromagnetic signal. The accumulated binding complex generates a compressive stress on the biosensor surface, resulting in a decrease in the biosensor’s static magnetic permeability, which correlates to the HSA concentrations. To improve the sensitivity of the biosensor, the concentration of NiFe2O4 nanofluid and the impregnated numbers of the NiFe2O4 nanofluid-impregnated papers were optimized. The experimental results demonstrated that the biosensor exhibited a linear response to HSA concentrations ranging from 10 μg∙mL−1 to 200 μg∙mL−1, with a detection limit of 0.43 μg∙mL−1, which is significantly lower than the minimal diagnosis limit of microalbuminuria. The NiFe2O4/paper-based ME biosensor is easy to fabricate, and allows the rapid, highly-sensitive, and selective detection of HSA, providing a valuable analytical device for early monitoring and clinical diagnosis of microalbuminuria and nephropathy. This study shows the successful integration of the paper-based biosensor and the ME sensing analytical method will be a highly-sensitive, easy-to-use, disposable, and portable alternative for point-of-care monitoring.

Exploring the feasibility of Salmonella Typhimurium-specific phage as a novel bio-receptor.

The purpose of this study was aimed to isolate a Salmonella Typhimurium-specific phage (KFS-ST) from washing water in a poultry processing facility and to investigate the feasibility of the KFS-ST as a novel bio-receptor for the magnetoelastic (ME) biosensor method. KFS-ST against S. Typhimurium was isolated, propagated, and purified using a CsCl-gradient ultracentrifugation. Morphological characteristics of KFS-ST were analyzed using transmission electron microscopy (TEM). Its specificity and efficiency of plating analysis were conducted against 39 foodborne pathogens. The temperature and pH stabilities of KFS-ST were investigated by the exposure of the phage to various temperatures (−70°C–70°C) and pHs (1–12) for 1 h. A one-step growth curve analysis was performed to determine the eclipse time, latent time and burst size of phage. The storage stability of KFS-ST was studied by exposing KFS-ST to various storage temperatures (−70°C, −20°C, 4°C, and 22°C) for 12 weeks. KFS-ST was isolated and purified with a high concentration of (11.47 ± 0.25) Log PFU/mL. It had an icosahedral head (56.91 ± 2.90 nm) and a non-contractile tail (225.49 ± 2.67 nm), which was classified into the family of Siphoviridae in the order of Caudovirales. KFS-ST exhibited an excellent specificity against only S. Typhimurium and S. Enteritidis, which are considered two of the most problematic Salmonella strains in the meat and poultry. However, KFS-ST did not exhibit any specificity against six other Salmonella and 27 non-Salmonella strains. KFS-ST was stable at temperature of 4°C to 50°C and at pH of 4 to 12. The eclipse time, latent time, and burst size of KFS-ST were determined to be 10 min, 25 min and 26 PFU/ infected cell, respectively. KFS-ST was relatively stable during the 12-week storage period at all tested temperatures. Therefore, this study demonstrated the feasibility of KFS-ST as a novel bio-receptor for the detection of S. Typhimurium and S. Enteritidis in meat and poultry products using the ME biosensor method.

Core-Shell Magnetic Nanoparticles for Highly Sensitive Magnetoelastic Immunosensor.

A magnetoelastic (ME) biosensor for wireless detection of analytes in liquid is described. The ME biosensor was tested against human IgG in the range 0–20 μg∙mL−1. The sensing elements, anti-human IgG produced in goat, were immobilized on the surface of the sensor by using a recently introduced photochemical immobilization technique (PIT), whereas a new amplification protocol exploiting gold coated magnetic nanoparticles (core-shell nanoparticles) is demonstrated to significantly enhance the sensitivity. The gold nanoflowers grown on the magnetic core allowed us to tether anti-human IgG to the nanoparticles to exploit the sandwich detection scheme. The experimental results show that the 6 mm × 1 mm × 30 μm ME biosensor with an amplification protocol that uses magnetic nanoparticles has a limit of detection (LOD) lower than 1 nM, works well in water, and has a rapid response time of few minutes. Therefore, the ME biosensor is very promising for real-time wireless detection of pathogens in liquids and for real life diagnostic purpose.

Real-time and label-free detection of VKORC1 genes based on a magnetoelastic biosensor for warfarin therapy.

Various thrombotic disorders have been treated with the anticoagulant warfarin. However, a small change in warfarin concentration may lead to drug adverse reactions or therapeutic failure due to its narrow therapeutic index. Therefore, the dose of warfarin must be monitored for each patient during therapy in real-time and in a sensitive and stable manner. In this work, we designed a magnetoelastic (ME) biosensor using Metglas alloy 2826 to detect VKORC1 genotypes, which is one of the most important known genetic determinants of warfarin dosing. The sensor enabled both fast responses to DNA binding and wireless transmission of signals. Specifically in the target recognition layer, the sensor introduced an avidin-biotin interaction system for signal amplification by increasing the surface load mass. The resonance frequency shift of the signal was linear to the concentration of the target in the range of 0.1 fM to 10 pM, with a detection limit (LOD) of 0.00389 fM (S/N = 3) and a sensitivity of 45.7 Hz pM-1. Importantly, this ME-based biosensor was small and portable without the use of any optical labels, which has high potential to be applied in advanced biomedical diagnosis of nucleic acids and proteins.

The Influences of Organic Matter Concentrations in Juices for Pathogen Detection Using Phage-Based Biosensors

Fruit and vegetables are playing an important role of today’s healthy diet. Juices are the liquid extracts from fruit and vegetables, which contain lots of organic matters, such as vitamins, minerals and plant chemicals (phytonutrients). Commercial bottle juices usually contain different percentages of real juices in their juice products. Therefore, the amount of organic matter content in juices are different in various brands of juices. The foodborne pathogen outbreaks through the consumption of fruit or vegetable juices continue to be reported (CDC, 2016). It indicates that pathogens like Salmonella can be packaged with juices even with current manufacture microbial-inactivation process. According to several studies, the acidity in tomatoes juice and the phyto-chemicals (like chlorophyll) from damage leaves in leafy greens samples can affect the sensitivity of pathogen detection in juices. For example, chlorophyll is one of the substances in leafy green juice that inhibits PCR reaction for pathogen detection. This made the pathogen detection in some juices a difficult task to achieve. The phage magnetoelastic (ME) biosensors are wireless sensors, whose resonance oscillation and resonance frequency are actuated and detected through magnetic fields. These biosensors have been shown to be highly sensitive and specific in pathogen detection including Salmonella on various food surfaces or liquids (Li et al., 2010). Therefore, in this study, different concentrations of juices from tomatoes and spinach with artificially spiked Salmonella (at the concentration of 104 cfu/ml) was tested by ME biosensors. The influence of pathogen detection capability was then studied by comparing the bacterial capture rates on biosensors. In tomato juice, the results showed that the capture rate of Salmonella can be reached up to 90.68% by using 100 ME biosensors in a tube rocking experiment with 10% tomato juice content. In spinach juice, the capture rate of Salmonella showed similar results as 90.68% in the same 10% juice concentration. However, when the juice concentration of spinach went up to 15% and 20%, the bacterial capture rate slightly decreased. The Salmonella capture rate were shown as 89.82% and 89.065, respectively. The decreasing of capture rate was obvious by using 50 ME sensors for the 15% and 20% spinach juices. In conclusion, by using 100 phage ME biosensors, the detection platform can detect as high as 89% Salmonella in high juice concentration (15 % and 20%) of both tomato and spinach juice samples. While in the moderate juice concentration zone (5-10%), the ME biosensors show very promising results of detecting 90% Salmonella in both juices.

Effect of the Number of ME Elements on Capture Rate of a Small Number of Pathogens in the Prototype of Phage Filter with a Comparison of Rocking Method

Foodborne illness is a frequent public health problem because there is potential for food to be contaminated by pathogens at any point from farms to the dinner tables. Each year, the cost of foodborne illness in the U.S. is enormous. The direct and indirect costs associated with foodborne illness are more than $15.6 billion per year. For rapid detection of foodborne pathogens, Magnetoelastic (ME) biosensor is one of the methods to detect pathogens on food surface and liquids. As the multistate outbreak caused by Romaine lettuce contamination in 2018, current microbiological testing methods, required by Food and Drug Administration (FDA)’s Bacteriological Analytical Manual (BAM), shows shortages. According to the requirement, a new method, named 3D bio-molecular filter, was developed to capture, concentrate, and isolate a small number of pathogens in large volume of liquid streams. The filter consists of ME filter elements, a pair of permanent magnetic plates, and testing glass tube. ME filter elements are magnetically held and arrayed in a testing glass tube. The target pathogen in a large volume of liquid will be capture by ME filter elements when a large volume of liquid passes through. A prototype of a compact edition was developed in this paper to support this method. The device consists of high magnetic plates, which provide uniform high magnetic force to hold ME filter elements, and a square glass tube to pass through the liquid with target pathogen. In this work, E2 phage is immobilized on ME filter elements to capture, concentrate, and isolate Salmonella Typhimurium in processing water. Two different methods to capture Salmonella, rocking method and 3D biomolecular filter method, are compared. The capture rate and effects of the number of ME filter elements on Salmonella capture efficiency will be discussed.

A Portable Device for Rapid Detection of Human Serum Albumin using an immunoglobulin-coating-based Magnetoelastic Biosensor

Abnormal protein concentration levels in human body fluids, such as urine, serum etc., are considered to associate with disease states, providing essential information for the pre-clinical diagnosis. This paper presents a wireless immunoglobulin-coated magnetoelastic (ME) biosensor for fast, cost-effective detections of human serum albumin (HSA) with small sample volumes at a microliter scale. This is the first portable resonant sensor based on magnetostrictive effect that can monitor different molecular states of HSA. Anti-HSA Immunoglobulin G (IgG) was immobilized on the surface of the ME sensor to selectively capture HSA. The rapid conjugation between the antibody and antigen changed the sensor surface states and thus induced resonance frequency shifts (RFS), which were monitored in real time for the qualitative and quantitative analysis of HSA. This paper brings forward a System on Chip (SoC)-based system architecture to realize the function of RFS sampling. The performance of the portable device was validated to be comparable to that of the Vector Network Analyzer (VNA) AV3620 using different concentrations of HSA solution. The RFS were linearly proportional to the HSA concentrations in the range from 0.1 to 100 μg/mL with a linearity up to 0.998, a sensitivity of 8.70 Hz/μg.mL-1 and a detection limit of 0.039 μg/mL, indicating good feasibility of this method. Meanwhile, the response of this portable ME biosensor was quick and specific to HSA targets. This ME biosensor shows high potential to be used in diagnosing abnormal HSA.