FIELD

This disclosure relates to a graphene based nano-composite biosensor system that utilizes the giant magnetoresistance (GMR) effect to detect biological molecules for real-time and remote diagnosis.

BACKGROUND

The phenomenon of magnetoresistance (MR) in metallic materials has been known for over a century. Magnetoresistance involves the change of electrical resistance in metals upon application of a magnetic field. The magnitude of the change in electrical resistance is dependent on the structure of the electrical orbitals at the Fermi surface. There are two possible electron states when they are in transition as per the Mott model: “spin-up” orientation and “spin-down” orientation. The total current flowing through a structure is the sum of the current carriers with “spin-up” orientation and the sum of current carriers with “spin-down” orientation.

As shown inFIG. 1A, if the “spin-up”104and “spin-down”106currents are flowing through the ferromagnetic layer, e.g. iron (Fe), cobalt (Co), nickel (Ni), with a fixed direction of magnetization (“up” or “down”), the resistance between the flow paths of the first101and second102groups of electrons will differ. Conventional magnetoresistance resistors have limited applications as they will exhibit a change of resistance of less than 3%.

The Giant magnetoresistance (GMR) effect was discovered in 1980 and was originally a system made of alternating layers of magnetic and non-magnetic substrates. A sample with a structure containing these alternating magnetic and non-magnetic substrates will be able to achieve a more significant change in the electrical resistance under the application of a magnetic field. The GMR effect is particularly useful in sensor applications, where GMR sensors display significant advantages over traditional Hall-effect sensors in terms of physical size, sensitivity, temperature stability, and cost.

The unique, microstructure-dependent properties of graphene and graphene based nanomaterials mean that it has high potential for application in various fields such as automobiles, electronic devices, and biomedical instrumentation and devices. In regard to applications with GMR sensors, graphene displays better conductivity in comparison to semiconductors and is an excellent spacing layer in multilayer GMR sensors.

A Mott model may be used to explain the GMR phenomenon. As shown inFIG. 1B, electrical resistance is maximized108when the magnetic moments of the ferromagnetic109and non-magnetic107layers are antiparallel112(no external magnetic field) and it is minimized110when the magnetic moments of the layers are parallel111(with an external magnetic field). This effect occurs due to the spin-dependent scattering of the conduction electrons. By knowing the contribution to the overall magnitude of resistance from each orientation, the GMR can then be determined.

The GMR effect has shown a wide array of potential applications in magnetoelectronics.FIG. 2A,FIG. 2B,FIG. 2CandFIG. 2Dshows the major types of GMR systems and substrates200within magnetoelectronics including multilayer GMR202, spin valve GMR204, pseudo-spin GMR206, and granular GMR208respectively.

The thickness of each substrate layer has a significant impact on the GMR value of the resistor. The parameters relating to the mean free path of the conduction electrons in the spacer layer, the spacer layer thickness, and the thickness of the non-magnetic layer all impact the GMR value. The experimental and theoretical results of existing work in this field indicate that the thinner the multilayer, the higher the GMR value. Consequently, nanostructured GMR multilayers have attracted extensive attention for their applications to miniaturization of systems, especially in the areas of spintronic, data storage and magnetic sensing.

The application of the GMR effect with graphene-based multilayers has demonstrated that separation between spin-down and spin-up carriers in graphene are realized and carriers are spin polarized. Significant research has been completed to design multi-layered systems made by graphene sandwiched between two layer of ferromagnetic materials, which can achieve >20% increase in MR.

The prior art relating to the formation of magnetoresistance sensors by using exfoliating graphene deposited with Au electrodes by using e-beam lithography is also well documented. It indicates the electrical resistance of this MR device increased over 3% when magnetic field is zero. The magnetic field-dependent electrical resistance of this enhanced magnetoresistance sensor made by graphene-based multilayers can detect the magnetic field in the range of 500 Oe to 1.5 KOe. Although graphene-based multilayers have shown well-controlled GMR effect, granular-matrix structures by loading magnetic nanocrystals onto non-magnetic substrate, i.e. graphene sheets, could be an alternative materials for achieving GMR effect.

The major advantage of granular GMR materials lies in their cost-effective processes of synthesis. Quite recently, giant magnetoresistance effects have been observed in nanocomposite systems. Guo et al. reported that magnetic graphene/iron/iron oxide nanocomposites prepared by thermal-decomposition can achieve the magnetoresistance with high values of 46%-72% at room temperature under 90 KOe.

Both theory studies and experimental studies relating to GMR systems have demonstrated the feasibility of graphene-based granular structures for magnetoresistive devices but there is still limited knowledge relating to the interaction between magnetic nanocrystals and graphene sheets to achieve GMR effect. The graphene-based system presented herein provides several advantageous features including device and system miniaturization, high precision deposition of the magnetic particles and the ability to wirelessly interface the bio-sensing device.

SUMMARY

The present disclosure relates to a graphene-based system with special magnetic properties that has the potential to broaden the scope of the application of graphene products in real-time and remote diagnosis sensors.

The system for detecting one or more target analytes comprises:a) a first resistor structure comprisinga substrate,a graphene-based nanocomposite material located on a surface of the substrate, the graphene-based nanocomposite material exhibiting one or more magnetoresistance properties,a surface of the graphene-based nanocomposite material including molecular sensing elements bound thereto which exhibit an affinity for binding with the target analytes, andelectrodes connected to the resistor structure connectable to a power source and a device for measuring a resistance across the resistor structure for sensing a giant magnetoresistance (GMR) value of the resistor structure;b) magnetic colloidal nanoparticles exhibiting preselected magnetic properties, an outer surface of the magnetic colloidal nanoparticles being modified to allow interaction with the surface of the resistor structure resulting in a change in the GMR value of the resistor structure;c) the resistor structure configured to be operably connected to,a magnetic field generating device configured to apply a magnetic field to the graphene-based nanocomposite wherein the field has a magnitude in a range from greater than 0 to about 5 Tesla;wherein a presence of target analytes in a vicinity of the surface of the resistor structure induces the interaction to occur by binding of the target analytes to the molecular sensing elements bound thereto causing a change in the GMR value of the resistor structure.

In one embodiment the outer surface of the magnetic colloidal nanoparticles may be modified to include molecular sensing elements bound thereto which exhibit an affinity for binding with the target analytes, and wherein when target analytes are present in a vicinity of the magnetic colloidal nanoparticles they bind to the molecular sensing elements on the magnetic colloidal nanoparticles, and when the magnetic colloidal nanoparticles with target analytes bound thereto are in a vicinity of the surface of the resister structure, the interaction with the surface is binding of the target analytes, bound to their respective magnetic colloidal nanoparticles, to the molecular sensing elements bound to the surface of the resistor structure.

In this embodiment the molecular sensing elements bound to the surface of the magnetic colloidal nanoparticles which exhibit an affinity for binding with the target analytes may include functional groups selected from the group consisting of hydrogen, hydroxyl, carboxyl, amine, amide, phosphate, thiol, methyl, and polyethylene glycol (PEG) derivatives.

In another embodiment the outer surface of the magnetic colloidal nanoparticles may modified to include competing molecules bound thereto which exhibit an affinity for binding with the molecular sensing elements bound to the surface of the resistor structure, and wherein when the target analytes are in a vicinity of the surface of the resister structure, the interaction with the surface is binding of the target analytes is displacement of the bound magnetic colloidal nanoparticles and binding of the target analytes to the molecular sensing elements bound to the surface of the resistor structure.

In this embodiment the competing molecules bound to the surface of the magnetic colloidal nanoparticles which exhibit an affinity for binding with the molecular sensing elements bound to the surface of the resistor structure may include functional groups selected from the group consisting of hydrogen, hydroxyl, carboxyl, amine, amide, phosphate, thiol, methyl, and polyethylene glycol (PEG) derivatives.

The magnetic colloidal nanoparticles may have a diameter in a range from about 1 nm to about 1000 nm.

The magnetic colloidal nanoparticles may be any one of Fe, Co, Ni, FexCoy(x+y=100), FexNiy(x+y=100), FePt, EuO, Eu1-xGdxSe (0.02≤x≤0.8), or Gd3-xS4(0≤x≤0.8) based nanoparticles.

The magnetic colloidal nanoparticles are any one of nanoparticles containing Fe, Co, or Ni, or core-shell magnetic nanoparticles including silica coated magnetic nanoparticles, gold coated magnetic nanoparticles, or chitosan-coated magnetic nanoparticles.

The substrate may be comprised of any one of a ceramic, a polymer or a metal. The ceramic may comprise of any one of SiC or glass, and wherein the polymer may comprise any one of polydimethylsiloxane (PDMS) or biopolymers.

The system may further comprise two or more additional resistor structures mounted on the substrate and connected in series with the first resistor structure and the power supply and the device for measuring resistance and magnetoresistance, and wherein the magnetic field generating device is configured to apply the same magnetic field to all of the resistor structures.

The electrodes may comprised of metals or carbon-based materials, and the metals may be any one of gold (Au), tungsten (W), platinum (Pt).

The molecular sensing elements bound to the surface of the graphene-based nanocomposite material may include any one or combination of a glucose binding protein, Concanavalin A, glucose oxidase enzyme, boronic acid, antibody, DNA sequences, and amyloid-β-derived diffusible ligands (ADDLs).

The one or more target analytes being detected for may include any one or combination of glucose, DNA, proteins, lipids, or microbes.

The graphene-based nanocomposites may be comprised of graphene nanosheets loaded with magnetic nanocrystals. The weight ratio of said graphene to said magnetic nanocrystals is in a range from about 2:98 to about 98:2.

The thickness of the graphene-based nanocomposite may be in a range from about 100 nm to about 5 mm.

The magnetic colloidal nanoparticles and graphene-based nanocomposites are selected such that the interaction between magnetic colloidal nanoparticles and graphene-based nanocomposites changes the magnetic field in a range from about 5 Oe to about 30 KOe.

In use the mixture containing magnetic colloidal nanoparticles may be introduced onto the surface of the resistor structure by a liquid dispenser which can be any one of a pipettor, a pump-connected microfluidic system, or a fluidic loop system.

In use the magnetic colloidal nanoparticles which are not bound on the surface of resistor structure after being exposed thereto are removed from the surface of the resistor structure by any one of aqueous-based washing solution, or a pumping solvent removal system, or vortex microfluidic technology.

During preparation of the resistor structure, a thickness of the graphene-based nanocomposite material may be controlled by use of a hydraulic press, a method of physical deposition, a method of chemical coating or a method of 3-D printing.

The magnetic colloidal nanoparticles may have a diameter in a range from about 1 nm to about 1000 nm.

The system may be configured to be connected to a wireless system for real-time and remote detection.

A further understanding of the functional and advantageous aspects of the present disclosure can be realized by reference to the following detailed description and drawings.

