Highly stable integration of graphene Hall sensors on a microfluidic platform for magnetic sensing in whole blood

Abstract

The detection and analysis of rare cells in complex media such as blood is increasingly important in biomedical research and clinical diagnostics. Micro-Hall detectors (μHD) for magnetic detection in blood have previously demonstrated ultrahigh sensitivity to rare cells. This sensitivity originates from the minimal magnetic background in blood, obviating cumbersome and detrimental sample preparation. However, the translation of this technology to clinical applications has been limited by inherently low throughput (<1 mL/h), susceptibility to clogging, and incompatibility with commercial CMOS foundry processing. To help overcome these challenges, we have developed CMOS-compatible graphene Hall sensors for integration with PDMS microfluidics for magnetic sensing in blood. We demonstrate that these graphene μHDs can match the performance of the best published μHDs, can be passivated for robust use with whole blood, and can be integrated with microfluidics and sensing electronics for in-flow detection of magnetic beads. We show a proof-of-concept validation of our system on a silicon substrate and detect magnetic agarose beads, as a model for cells, demonstrating promise for future integration in clinical applications with a custom CMOS chip.

Minimizing Contact Resistance and Flicker Noise in Micro Graphene Hall Sensors Using Persistent Carbene Modified Gold Electrodes

“…Here, we report on the application of persistent carbene to mitigate contact noise at the graphene-gold electrode interface, achieving a reduction in the flicker noise of the μGHS by a factor of 1000 to 3.13 × 10 –14 V 2 /Hz and an improvement in the magnetic LOD S B 1/2 to 1440 nT/Hz 1/2 at 1 kHz with a 100 μA bias current. Remarkably, our approach significantly reduces contact resistance by an order of magnitude and decreases flicker noise in μGHSs by a factor of 5 as compared to previous reports. ,, These enhancements are ascribed to the π–π stacking interaction and reduced work function difference between the persistent carbene-treated gold electrode and graphene, as verified through Kelvin probe force microscopy (KPFM) analysis. By integrating a microcoil into the μGHS, we have achieved real-time detection of superparamagnetic nanoparticles, marking a significant advancement in detecting magnetic biomarkers such as ferritin.…”

“…The S V exhibits a distinct 1/ f behavior and increases with I xx (Figure S3b), in agreement with Hooge’s empirical model. , Within the 0–10 mM IPr concentration range, an increase in IPr concentration leads to decreased flicker noise, while further increasing to 15 mM results in an elevated noise level, aligning with the trend of contact resistivity across varying IPr concentrations. For μGHS treated with an optimal IPr concentration of 10 mM, the flicker noise PSD at a 100 μA I xx bias is found to be 3.13 × 10 –14 V 2 /Hz, marking a significant enhancement by a factor of 1000 over untreated devices, and by a factor of 5 compared to the scalable μGHSs of previous studies. , Our work is the first attempt ever reported to optimize the contact noise of scalable μGHSs, providing a new pathway toward low-noise magnetic field sensing.…”

“…For μGHS treated with an optimal IPr concentration of 10 mM, the flicker noise PSD at a 100 μA I xx bias is found to be 3.13 × 10 −14 V 2 /Hz, marking a significant enhancement by a factor of 1000 over untreated devices, and by a factor of 5 compared to the scalable μGHSs of previous studies. 11,32 Our work is the first attempt ever reported to optimize the contact noise of scalable μGHSs, providing a new pathway toward low-noise magnetic field sensing.…”

“…Remarkably, our approach significantly reduces contact resistance by an order of magnitude and decreases flicker noise in μGHSs by a factor of 5 as compared to previous reports. 11,28,32 electrode and graphene, as verified through Kelvin probe force microscopy (KPFM) analysis. By integrating a microcoil into the μGHS, we have achieved real-time detection of superparamagnetic nanoparticles, marking a significant advancement in detecting magnetic biomarkers such as ferritin.…”

“…Magnetic substances present in body fluid, particularly ferritin, hold significant promise as biomarkers for the label-free diagnosis of early stage diseases, such as hereditary hemochromatosis (HHC). − A micro Hall detector (μHD) offers a high signal-to-noise ratio (SNR), excellent linearity in magnetic response, and CMOS compatibility, making it a promising platform for biomagnetic sensing. − The performance of the μHD is expected to be further enhanced when integrated with two-dimensional (2D) graphene materials. Unlike traditional semiconducting materials, graphene exhibits increased carrier mobility as carrier density decreases, − a unique characteristic making it an ideal nanomaterial for scalable fabrication of μHDs with high performance.…”