Development of a Microfluidic Chip System with Giant Magnetoresistance Sensor for High-Sensitivity Detection of Magnetic Nanoparticles in Biomedical Applications

Abstract

Magnetic nanoparticles (MNPs) have been widely utilized in the biomedical field for numerous years, offering several advantages such as exceptional biocompatibility and diverse applications in biology. However, the existing methods for quantifying magnetic labeled sample assays are scarce. This research presents a novel approach by developing a microfluidic chip system embedded with a giant magnetoresistance (GMR) sensor. The system successfully detects low concentrations of MNPs with magnetic particle velocities of 20 mm/s. The stray field generated by the magnetic subject flowing through the microchannel above the GMR sensor causes variations in the signals. The sensor's output signals are appropriately amplified, filtered, and processed to provide valuable indications. The integration of the GMR microfluidic chip system demonstrates notable attributes, including affordability, speed, and user-friendly operation. Moreover, it exhibits a high detection sensitivity of 10 μg/μL for MNPs, achieved through optimizing the vertical magnetic field to 100 Oe and the horizontal magnetic field to 2 Oe. Additionally, the study examines magnetic labeled RAW264.7 cells. This quantitative detection of magnetic nanoparticles can have applications in DNA concentration detection, protein concentration detection, and other promising areas of research.

Keywords: magnetic particles; magnetoresistive sensors; microfluidics.

Figure 1

Schematic diagram of the integrated GMR microfluidic chip system, including the solution pump, detection area, and display device. The CCD camera monitors the flow of MNPs. The middle section represents the microfluidic channel. The lower part features a permanent magnet for magnetizing the superparamagnetic MNPs. The upper left inset shows the real image of the GMR microfluidic chip, while the lower left inset illustrates the MNP under the applied magnetic field (blue arrow), resulting in magnetization in the same direction (red arrow). The white arrow indicates the direction of the magnetization of the GMR, and the green arrow indicates the direction of the microfluidic flow.

Figure 2

(a) The fabrication process of the microfluidic MNP detection chip. The lock-in MNP detection system containing the solution pump, detection area, and lock-in amplifier; (b) the schematic diagram of the microfluidic chip with a microchannel for magnetic nanoparticle flowing and the sensor chip and a readout circuit. (c) The external magnet was applied for alternative magnetization of MNPs.

Figure 3

SEM image of (a) MNPs and (b) dextran-coated MNP particles. (c) SQUID magnetic hysteresis loops of magnetic nanoparticles (MNPs) and dextran-coated MNPs (DEX-MNPs). Magnetization ratio of DEX-MNPs and MNPs was about 0.21 (15.39/73.64). (d) ZFC/FC curves for MNP samples with an applied field of 100 Oe (TB = 71.82 K).

Figure 4

(a) Integration of the GMR microfluidic chip system comprising the solution pump, detection area, and data display device. The upper right inset shows the photo of the data display device. The signal processing circuit design (lower left) includes a differential amplifier, high-pass filter, low-pass filter, and amplifier with a total gain of 75 dB. (b) The LabVIEW software enables data synchronization from the microprocessor and display on the computer. Signal vibrations are observed on the front panel of LabVIEW when MNPs pass through the GMR microfluidic chip.

Figure 5

The picture of MNPs (a) close to the GMR sensor, (b) above the GMR sensor, and (c) pass the GMR sensor. The pictures in the lower left corner are the instant signal image. (d) The signal diagram of three consecutive 250 ug/mL MNPs passing through the sensor.

Figure 6

(a) The voltage signal of different MNP concentrations. It could be seen that, the higher the concentration of MNPs, the stronger the signal. (b) The linear relationship between the concentration of MNPs and the voltage. The coefficient of determination R² was 0.99984.

Figure 7

(a) Prussian blue staining results of RAW cells internalizing magnetic nanoparticles (MNPs) for 12 h. (b) Control corresponds to the RAW cells that were not treated with MPs in parallel to the treated group. (c) Cell velocity distributions of 510 magnetically labeled cells. Insets: consecutive optical micrographs of mobile cells at different time points. Scale bar represents 10 μm. (d) The measured signals responding to the magnetic-labeled RAW cells passing through the microfluidic chip system.