Alejandro Ruiz
580 California St., Suite 400
San Francisco, CA, 94104
Detection of low-concentration superparamagnetic nanoparticles using an integrated radio frequency magnetic biosensor
2013, Journal of Applied Physics
https://doi.org/10.1063/1.4795134visibility
…
description
6 pages
link
1 file
Sign up for access to the world's latest research
checkGet notified about relevant papers
checkSave papers to use in your research
checkJoin the discussion with peers
checkTrack your impact
Abstract
Improving the sensitivity of existing biosensors for highly sensitive detection of magnetic nanoparticles as biomarkers in biological systems is an important and challenging task. Here, we propose a method of combining the magneto-resistance (MR), magneto-reactance (MX), and magneto-impedance (MI) effects to develop an integrated magnetic biosensor with tunable and enhanced sensitivity. A systematic study of the 7 nm Fe3O4 nanoparticle concentration dependence of MR, MX, and MI ratios of a soft ferromagnetic amorphous ribbon shows that these ratios first increase sharply with increase in particle concentration (0–124 nM) and then remain almost unchanged for higher concentrations (124 nM–1240 nM). The MX-based biosensor shows the highest sensitivity. With this biosensor, ∼2.1 × 1011 7 nm Fe3O4 nanoparticles can be detected over a detection area of 2.0 × 105 μm2, which is comparable to a superconducting quantum interference device biosensor that detects the presence of ∼1 × 108 11 nm ...
Related papers
A highly sensitive magnetic biosensor for detection and quantification of anticancer drugs tagged to superparamagnetic nanoparticles
Journal of Applied Physics, 2014
We report on a highly sensitive magnetic biosensor based on the magneto-reactance (MX) effect of a Co 65 Fe 4 Ni 2 Si 15 B 14 amorphous ribbon with a nanohole-patterned surface for detection and quantification of anticancer drugs (Curcumin) tagged to superparamagnetic (Fe 3 O 4 ) nanoparticles. Fe 3 O 4 nanoparticles (mean size, $10 nm) were first coated with Alginate, and Curcumin was then tagged to the nanoparticles. The detection and quantification of Curcumin were assessed by the change in MX of the ribbon subject to varying concentrations of the Fe 3 O 4 nanoparticles to which Curcumin was tagged. A high capacity of the MX-based biosensor in quantitative analysis of Curcumin-loaded Fe 3 O 4 nanoparticles was achieved in the range of 0-50 ng/ml, beyond which the detection sensitivity of the sensor remained unchanged. The detection sensitivity of the biosensor reached an extremely high value of 30%, which is about 4-5 times higher than that of a magneto-impedance (MI) based biosensor. This biosensor is well suited for detection of low-concentration magnetic biomarkers in biological systems. V C 2014 AIP Publishing LLC.
GMR sensors: Magnetoresistive behaviour optimization for biological detection by means of superparamagnetic nanoparticles
Biosensors and Bioelectronics, 2011
An immunomagnetic method for the selective and quantitative detection of biological species by means of a magnetoresistive biosensor and superparamagnetic particles has been optimized. In order to achieve this, a giant magnetoresistive [Co (5.10 nm)/Cu (2.47 nm)] 20 multilayer structure has been chosen as the sensitive material, showing a magnetoresistance of 3.60% at 215 Oe and a sensitivity up to 0.19 /Oe between 145 Oe and 350 Oe. The outward gold surface of the sensor is biofunctionalized with a Self-Assembled Monolayer (SAM).
Ultrasensitive Magnetic Nanoparticle Detector for Biosensor Applications
Sensors (Basel, Switzerland), 2017
Ta/Ru/Co/Ru/Co/Cu/Co/Ni80Fe20/Ta spin-valve giant magnetoresistive (GMR) multilayers were deposited using UHV magnetron sputtering and optimized to achieve a 13% GMR ratio before patterning. The GMR multilayer was patterned into 12 sensor arrays using a combination of e-beam and optical lithographies. Arrays were constructed with 400 nm × 400 nm and 400 nm × 200 nm sensors for the detection of reporter nanoparticles. Nanoparticle detection was based on measuring the shift in high-to-low resistance switching field of the GMR sensors in the presence of magnetic particle(s). Due to shape anisotropy and the corresponding demag field, the resistance state switching fields were significantly larger and the switching field distribution significantly broader in the 400 nm × 200 nm sensors as compared to the 400 nm × 400 nm sensors. Thus, sensor arrays with 400 nm × 400 nm dimensions were used for the demonstration of particle detection. Detection of a single 225 nm Fe₃O₄ magnetic nanopartic...
Perspective: Magnetoresistive sensors for biomedicine
Journal of Applied Physics
Currently, there is a plethora of sensors (e.g., electrochemical, optical, and piezoelectric) used in life sciences for either analyte detection or diagnostic purposes, but in the last decade, magnetic biosensors have received extended interest as a promising candidate for the development of nextgeneration, highly sensitive biomedical platforms. This approach is based on magnetic labeling, replacing the otherwise classic fluorescence labeling, combined with magnetic sensors that detect the stray field of the superparamagnetic markers (e.g., magnetic micro-nanoparticles or magnetic nanostructures). Apart from the increased sensitivity, magnetic biosensors exhibit the unique ability of controlling and modulating the superparamagnetic markers by an externally applied magnetic force as well as the capability of compact integration of their electronics on a single chip. The magnetic field sensing mechanism most widely investigated for applications in life sciences is based on the magnetoresistance (MR) effect that was first discovered in 1856 by Lord Kelvin. However, it is the giant magnetoresistance effect, discovered by Gr€ unberg and Fert in 1988, that actually exhibits the greatest potential as a biosensing principle. This perspective will shortly explain the magnetic labeling method and will provide a brief overview of the different MR sensor technologies (giant magnetoresistive, spin valves, and tunnel magnetoresistive) mostly used in biosensing applications as well as a compact assessment of the state of the art. Newly implemented innovations and their broad-ranging implications will be discussed, challenges that need to be addressed will be identified, and new hypotheses will be proposed.
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
Biosensors and Bioelectronics, 2018
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-Fe 2 O 3 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.
Magnetic particle-based ultrasensitive biosensors for diagnostics
Expert Review of Molecular Diagnostics, 2012
The process of sensitive and accurate detection of small quantities of disease biomarkers is critical for the clinical diagnosis of disease. In this regard, magnetic particles (MPs) have been widely used because of their unique magnetic properties allowing for efficient target capture, enrichment and convenient separation. These properties, coupled with great signal amplification, have enabled MP-based biosensors to achieve ultrasensitivities. Over the past few years, several ultrasensitive MP-based biosensors suitable for early clinical diagnostics have been reported. This article highlights some of the most recent developments, with a focus on MP-based ultrasensitive assays that use an antibody or aptamer as the target-binding agent, and that utilize efficient signal amplification/readout strategies.
Magnetoimpedance Biosensors and Real-Time Healthcare Monitors: Progress, Opportunities, and Challenges
Biosensors
A small DC magnetic field can induce an enormous response in the impedance of a soft magnetic conductor in various forms of wire, ribbon, and thin film. Also known as the giant magnetoimpedance (GMI) effect, this phenomenon forms the basis for the development of high-performance magnetic biosensors with magnetic field sensitivity down to the picoTesla regime at room temperature. Over the past decade, some state-of-the-art prototypes have become available for trial tests due to continuous efforts to improve the sensitivity of GMI biosensors for the ultrasensitive detection of biological entities and biomagnetic field detection of human activities through the use of magnetic nanoparticles as biomarkers. In this review, we highlight recent advances in the development of GMI biosensors and review medical devices for applications in biomedical diagnostics and healthcare monitoring, including real-time monitoring of respiratory motion in COVID-19 patients at various stages. We also discus...
Giant Magnetoresistive Biosensors for Time-Domain Magnetorelaxometry: A Theoretical Investigation and Progress Toward an Immunoassay
Scientific reports, 2017
Magnetorelaxometry (MRX) is a promising new biosensing technique for point-of-care diagnostics. Historically, magnetic sensors have been primarily used to monitor the stray field of magnetic nanoparticles bound to analytes of interest for immunoassays and flow cytometers. In MRX, the magnetic nanoparticles (MNPs) are first magnetized and then the temporal response is monitored after removing the magnetic field. This new sensing modality is insensitive to the magnetic field homogeneity making it more amenable to low-power portable applications. In this work, we systematically investigated time-domain MRX by measuring the signal dependence on the applied field, magnetization time, and magnetic core size. The extracted characteristic times varied for different magnetic MNPs, exhibiting unique magnetic signatures. We also measured the signal contribution based on the MNP location and correlated the coverage with measured signal amplitude. Lastly, we demonstrated, for the first time, a G...
Biosensing Using Magnetic Particle Detection Techniques
Sensors (Basel, Switzerland), 2017
Magnetic particles are widely used as signal labels in a variety of biological sensing applications, such as molecular detection and related strategies that rely on ligand-receptor binding. In this review, we explore the fundamental concepts involved in designing magnetic particles for biosensing applications and the techniques used to detect them. First, we briefly describe the magnetic properties that are important for bio-sensing applications and highlight the associated key parameters (such as the starting materials, size, functionalization methods, and bio-conjugation strategies). Subsequently, we focus on magnetic sensing applications that utilize several types of magnetic detection techniques: spintronic sensors, nuclear magnetic resonance (NMR) sensors, superconducting quantum interference devices (SQUIDs), sensors based on the atomic magnetometer (AM), and others. From the studies reported, we note that the size of the MPs is one of the most important factors in choosing a ...
Giant Magnetioimpedance in Co-Based Amorphous Ribbons Coated in Magnetic Nanoparticles for Biosensing Applications
2011
We report upon the enhancement of the giant magnetoimpedance (GMI) effect in Co-based amorphous ribbons coated with non-magnetic carbon nanotubes (CNTs). In our study, the CNTs were drop-casted onto the surface of a Metglas V R 2714 A ribbon with three different concentrations (5, 10, and 15 lL of CNTs). Relative to the plain ribbon, a 15% enhancement of the GMI effect was observed in the ribbon coated with 10 lL of CNTs. The GMI effect first increased with the CNT concentration, to a maximum of 10 lL of CNTs, and then decreased at higher concentrations. Noticeably, at a measured frequency of 10 MHz, the magnetic field-induced ac resistance change was about 35% larger for the ribbon coated with 10 lL of CNTs than for the plain ribbon. These observations may reveal a new perspective for developing CNT-based gas sensors that operate using the principle of the GMI effect. V C 2012 American Institute of Physics.
Cited by
A highly sensitive magnetic biosensor for detection and quantification of anticancer drugs tagged to superparamagnetic nanoparticles
Journal of Applied Physics, 2014
We report on a highly sensitive magnetic biosensor based on the magneto-reactance (MX) effect of a Co 65 Fe 4 Ni 2 Si 15 B 14 amorphous ribbon with a nanohole-patterned surface for detection and quantification of anticancer drugs (Curcumin) tagged to superparamagnetic (Fe 3 O 4 ) nanoparticles. Fe 3 O 4 nanoparticles (mean size, $10 nm) were first coated with Alginate, and Curcumin was then tagged to the nanoparticles. The detection and quantification of Curcumin were assessed by the change in MX of the ribbon subject to varying concentrations of the Fe 3 O 4 nanoparticles to which Curcumin was tagged. A high capacity of the MX-based biosensor in quantitative analysis of Curcumin-loaded Fe 3 O 4 nanoparticles was achieved in the range of 0-50 ng/ml, beyond which the detection sensitivity of the sensor remained unchanged. The detection sensitivity of the biosensor reached an extremely high value of 30%, which is about 4-5 times higher than that of a magneto-impedance (MI) based biosensor. This biosensor is well suited for detection of low-concentration magnetic biomarkers in biological systems. V C 2014 AIP Publishing LLC.
Surface plasmon resonances of protein-conjugated gold nanoparticles on graphitic substrates
Applied Physics Letters, 2013
A novel approach for detection and quantification of magnetic nanomarkers using a spin valve GMR-integrated microfluidic sensor
RSC Advances
We demonstrate the application of a spin valve giant magneto-resistance (GMR) integrated microfluidic sensor for the detection and quantification of superparamagnetic nanomarkers. A microfluidic channel containing the magnetic fluid, micro-conductors (MCs) for collection of magnetic markers and a spin valve GMR sensor for detecting the presence of magnetic stray field were integrated into a single chip and employed for detection of various concentrations of Nanomag-D beads of 250 nm diameter. The results show that the sensor is capable of detecting concentrations as low as 500 pg/ul of Nanomag-D beads and quantifying them in a linear scale over a wide particle concentration range (1 ng/ul - 500 ng/ul). Our study provides a novel platform towards the development of a portable lab-on-a-chip sensor.
Magnetoimpedance Biosensors and Real-Time Healthcare Monitors: Progress, Opportunities, and Challenges
Biosensors
A small DC magnetic field can induce an enormous response in the impedance of a soft magnetic conductor in various forms of wire, ribbon, and thin film. Also known as the giant magnetoimpedance (GMI) effect, this phenomenon forms the basis for the development of high-performance magnetic biosensors with magnetic field sensitivity down to the picoTesla regime at room temperature. Over the past decade, some state-of-the-art prototypes have become available for trial tests due to continuous efforts to improve the sensitivity of GMI biosensors for the ultrasensitive detection of biological entities and biomagnetic field detection of human activities through the use of magnetic nanoparticles as biomarkers. In this review, we highlight recent advances in the development of GMI biosensors and review medical devices for applications in biomedical diagnostics and healthcare monitoring, including real-time monitoring of respiratory motion in COVID-19 patients at various stages. We also discus...
Related papers
Advances in Magnetoresistive Biosensors
Micromachines, 2019
Magnetoresistance (MR) based biosensors are considered promising candidates for the detection of magnetic nanoparticles (MNPs) as biomarkers and the biomagnetic fields. MR biosensors have been widely used in the detection of proteins, DNAs, as well as the mapping of cardiovascular and brain signals. In this review, we firstly introduce three different MR devices from the fundamental perspectives, followed by the fabrication and surface modification of the MR sensors. The sensitivity of the MR sensors can be improved by optimizing the sensing geometry, engineering the magnetic bioassays on the sensor surface, and integrating the sensors with magnetic flux concentrators and microfluidic channels. Different kinds of MR-based bioassays are also introduced. Subsequently, the research on MR biosensors for the detection of protein biomarkers and genotyping is reviewed. As a more recent application, brain mapping based on MR sensors is summarized in a separate section with the discussion of...
Spin valve sensors for ultrasensitive detection of superparamagnetic nanoparticles for biological applications
Sensors and actuators. A, Physical, 2006
We present giant magnetoresistance (GMR) spin valve sensors designed for detection of superparamagnetic nanoparticles as potential biomolecular labels in magnetic biodetection technology. We discuss the sensor design and experimentally demonstrate that as few as approximately 23 monodisperse 16-nm superparamagnetic Fe(3)O(4) nanoparticles can be detected by submicron spin valve sensors at room temperature without resorting to lock-in detection. A patterned self-assembly method of nanoparticles, based on a polymer-mediated process and fine lithography, is developed for the detection. It is found that sensor signal increases linearly with the number of nanoparticles.
Magneto-impedance biosensor with enhanced sensitivity for highly sensitive detection of nanomag-D beads
A magnetoimpedance (MI) biosensor based on Co-based amorphous ribbon was designed and tested to detect functionalized Nanomag-D magnetic beads. While previous studies were focused mainly on exploring the MI change for biosensing, we show that the sensitivity of the biosensor can be enhanced when the change in ac magnetoresistance (MR) or magnetoreactance (MX) is used. The frequency at which the sensitivity of the sensor is optimized can be tuned. This is of potential interest in developing functional biosensors with improved sensitivity and tunable frequency.
In-Vitro Magnetoresistive Biosensors for Single Molecular Based Disease Diagnostics: Optimization of Sensor Geometry and Structure
Intelligent and Biosensors, 2010
Magnetoimpedance biosensor for Fe[sub 3]O[sub 4] nanoparticle intracellular uptake evaluation
Applied Physics Letters, 2007
Different signatures between chemically and biologically synthesized nanoparticles in a magnetic sensor: A new technology for multiparametric detection
Sensors and Actuators B: Chemical, 2010
A magnetic sensor, called MIAplex ® , has been developed by the company Magnisense. This instrument measures a signal, which is proportional to the second derivative of a magnetization curve. We show that this sensor is able to discriminate between the signature of small superparamagnetic nanoparticles produced chemically and that of larger ferromagnetic nanoparticles produced by magnetotactic bacteria. The reason why this distinction is possible comes from the different magnetization curves of these two types of nanoparticles. These results pave the way for the simultaneous detection of different types of biological molecules or living organisms.
Multiplexed detection for biomolecules tagged to magnetic nanoparticles using a miniaturized AC magnetic susceptometer
2009 IEEE Sensors, 2009
A novel multiplexed sensing scheme based on Brownian relaxation for biomolecules tagged to magnetic nanoparticles (MNPs) in liquid environment is proposed. Feasibility of the technique has been verified by the experiments with the mixture of differently sized magnetic nanoparticles using a newly developed room temperature, miniaturized AC magnetic susceptometer. The AC magnetic susceptibility measurements of Brownian relaxation of MNPs verify the sensing modality that proves the resonant frequency of imaginary susceptibility is inversely proportional to effective hydrodynamic size of MNPs. The proposed Brownian sensing scheme has the potential for multiplexed analysis of multiple biological binding events on functionalized MNPs. The performances were verified for individual and mixtures of monodisperse iron oxide MNPs in solution with carboxylic acid group with core diameters of 15, 25, 35, 50nm using the proposed susceptometer. The approach is readily compatible with lab-on-chip applications in medical diagnostics, and can be used for affinity-based biosensing. I.
Magnetoimpedance biosensor for Fe3O4 nanoparticle intracellular uptake evaluation
Applied Physics Letters, 2007
Iron oxide ͑Fe 3 O 4 ͒ nonspecific nanoparticles of 30 nm are embedded inside human embryonic kidney ͑HEK 293͒ cells by intracellular uptake with a concentration of ϳ10 5 particles/cell. An amorphous ribbon of Co 64.5 Fe 2.5 Cr 3 Si 15 B 15 exhibiting large magnetoimpedance ͑MI͒ serves as the sensing element. The presence of fringing fields of the nanoparticles changes the superposition of the constant applied field and the alternating field created by a current flowing through the ribbon that can be detected as a change in MI. This response is clearly dependent on the presence of the magnetic nanoparticles inside the cells and on the value of the external field.
Magnetic sensing technology for molecular analyses
Lab on a chip, 2014
Magnetic biosensors, based on nanomaterials and miniature electronics, have emerged as a powerful diagnostic platform. Benefiting from the inherently negligible magnetic background of biological objects, magnetic detection is highly selective even in complex biological media. The sensing thus requires minimal sample purification and yet achieves a high signal-to-background contrast. Moreover, magnetic sensors are also well-suited for miniaturization to match the size of biological targets, which enables sensitive detection of rare cells and small amounts of molecular markers. We herein summarize recent advances in magnetic sensing technologies, with an emphasis on clinical applications in point-of-care settings. Key components of sensors, including magnetic nanomaterials, labeling strategies and magnetometry, are reviewed.
Spin-Valve based magnetoresistive nanoparticle detector for applications in biosensing
Sensors and Actuators A-physical, 2017
GMR (giant magnetoresistance) sensor arrays were developed for the detection of magnetic nanoparticle reporters for biosensing applications. The sensor design was optimized to enable sharp transitions from low-to-high and high-to-low magnetoresistance states. The shift in these transitions under the influence of nanoparticle generated stray fields is used to detect the nanoparticles. Detection of a single 500 nm Fe3O4 magnetic nanoparticle and a small number (~10) of 500 nm nanoparticles was demonstrated using GMR sensors. With appropriate functionalization for biomolecular recognition, the developed GMR sensor arrays can serve as the basis of high-performance chemical and biological sensors. A magnetoresistive sensor platform for the detection of individual magnetic reporter particles is presented. The sensing scheme is based on the detection of the shift in the sensor's magnetoresistance-switching field in the presence of magnetic particle(s). A bottompinned spin-valve multilayer (Co/Ru/Co)/Cu/(Co/Ru/Co) device structure (with Ta/Ru seed and Ta capping layers) used for the sensor was deposited using ultra-high vacuum magnetron sputtering and patterned using conventional microfabrication techniques. Inexpensive electronics to measure device magnetoresistance (using DC currents) was used for testing. The detection of individual 500nm Fe3O4 nanoparticles as well as the detection of up to ten (10) nanoparticles was demonstrated and verified using scanning electron microscopy (SEM). The developed sensors are readily integratable into a biosensing platform for the detection of biomolecules at ultra-low concentration using magnetic nanoparticles as reporters.
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.