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Research on novel biosensors based on the GMR effect

2026-04-06 04:12:00 · · #1
1. Introduction GMR-based spin valve biomagnetic sensors, due to their high sensitivity, good linearity, and ease of integration, offer significant advantages in detection accuracy compared to earlier electrochemical analysis and piezoelectric crystal detection methods. Furthermore, compared to current mature fluorescence detection biological systems, they do not rely on large and sophisticated optical systems. Therefore, their research and application prospects have attracted considerable attention and optimism from numerous research institutions and scholars both domestically and internationally. In 1998, Naval Research Laboratory in the United States developed the first-generation BARC (bead array counter) chip, which has since evolved to the point where it can achieve DNA detection and nanomagnetic ball detection. 2. Biosensor Fabrication and Testing Since the detected signal is relatively small, only on the order of μV, a Wheatstone AC bridge was used as the detection structure in the design, and a complete detection system was built, as shown in Figure 1. The system consists of a GMR detection bridge, a driving section, and a detection section. The Wheatstone bridge consists of identical GMR spin valve sensitive resistors Rsen and Rref, and external adjustable reference resistors R1 and R2. The upper arms of the bridge, i.e., the magnetoresistive resistors Rsen and Rref, are integrated onto the chip using a three-step photolithography method. Their spin valve structure is Ta/NiFe/CoFe/Cu/CoFe/MnIr/Ta, with a magnetoresistance change rate (MR) of up to 9.2%, as shown in Figure 2. During testing, an AC signal is generated by a signal generator, which drives an electromagnet through a current amplification unit to produce a fixed-frequency alternating excitation magnetic field. Superparamagnetic immunomagnetic beads with a concentration of 200 μg/mL and a diameter of 2 μm are added to Rsen in the form of an alcohol solution. Under the influence of the external alternating excitation magnetic field, the magnetic beads attached to the surface of Rsen are magnetized, generating a small additional field of the same frequency. This causes a difference in the magnitude of the magnetic field induced in the two arms of the bridge, Rsen and Rref, resulting in a change in the output signal of the AC detection bridge. The signal from the AC bridge is ultimately detected by a lock-in amplifier and output to a computer for recording, thus enabling the detection of the immunomagnetic bead solution. Furthermore, since alcohol, used as a solvent for the immunomagnetic beads, also affects the sensor's output signal, its influence must be tested before the amplitude of the immunomagnetic bead output signal can be determined. 3. Experimental Results and Discussion 3.1 Measurement without Immunomagnetic Bead Solution To eliminate the influence of factors other than the immunomagnetic beads on the biosensor's output, measurements were first performed without the immunomagnetic bead solution. The specific results are shown in Figure 3. As can be seen from the figure, a background signal with an amplitude of approximately 20 μV exists during the detection process. This is mainly due to the incomplete matching of the Rsen and Rref arms. Although DC balancing of the bridge was performed before the experiment, the magnetoresistance curves of the two arms could not completely overlap, resulting in inconsistent responses to the alternating excitation magnetic field. Moreover, due to the varying degrees of matching of Rsen and Rref on different chips, the magnitude of the background signal varied in each experiment, but it remained stable in each specific experiment. During the solution addition process, the output signal exhibits a brief spike of approximately 50 μV before returning to the background level. This is primarily due to temperature changes on the sensor surface during solution addition and evaporation. However, this spike signal is not stable and therefore does not affect the final measurement result. 3.2 Measurement with Immunomagnetic Bead Solution After adding 1 μL of an immunomagnetic bead solution with a mass concentration of 200 μg/mL to the Rsen surface, the surface morphology of the biosensor is shown in Figure 4, and its output is shown in Figure 5. As can be seen from Figure 5, the magnetic beads attached to the surface of the GMR biosensor during the first addition resulted in a bridge output of 300 μV. Due to the relatively large surface area of ​​the sensor compared to the magnetic beads, some magnetic beads continued to adhere to the sensor surface during the second and third additions, further increasing the sensor output to a final value of 450 μV. Although the sensor surface was not completely covered by the magnetic spheres at this point, the newly added liquid had a certain rinsing effect on the existing magnetic spheres. Therefore, when the fourth drop was added, the number of magnetic spheres on the sensor surface did not increase further, and the sensor signal output reached its maximum value. Considering the influence of the background signal, the final signal amplitude generated by the immunomagnetic spheres should be 300 μV. This detection result is similar to the detection result of 2 μm magnetic spheres by Graham's group at INESC using a DC method. 3.3 Signal variation with excitation frequency In the experiment, the selection of the excitation field frequency also affects the output of the sensor signal. When the frequency of the applied excitation field is too high, the output signal of the bridge is significantly weakened due to the influence of inductive impedance components such as electromagnets in the system. However, considering the circuit noise of the system, especially the rapid increase of 1/f noise at lower frequencies, the applied excitation frequency should not be too low. The effect of the applied excitation frequency on the output is shown in Figure 6. The frequency selected in the experiment was 70 Hz, which has moderate signal and noise and the highest signal-to-noise ratio. 4. Conclusion A GMR sensor was fabricated using a three-step photolithography process. Preliminary detection was performed on bio-immunomagnetic beads with a diameter of 2 μm and a concentration of 200 μg/mL using AC detection. The results showed that the solution without magnetic beads caused signal fluctuations, but did not affect the final stable output of the sensor. After attaching magnetic beads to the sensor surface, a signal output of 350 μV was generated, which increased to 450 μV with increasing drop counts, eventually reaching saturation. Furthermore, higher and lower frequencies caused a decrease in the sensor output signal and an increase in system noise, respectively; therefore, a suitable frequency is also an important condition for optimizing the output signal.
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