A CMOS 10kpixel baseline-free magnetic bead detector with column-parallel readout for miniaturized immunoassays

The specific detection of anti-bodies or proteins in a point-of-care setting remains an unsolved technological challenge. While laboratory instruments rely on enzymatic labels and require complex, difficult-to-miniaturize optics, devices using super-paramagnetic labels have emerged as an attractive alternative for point-of-care systems [1]. The key challenge for all magnetic-bead detection systems [2-5] is the presence of a large measurement “baseline.” Since beads are paramagnetic, a polarization field must be applied in order to excite a magnetic response. This response is ~1000× smaller than the polarization field, necessitating a combination of calibration, reference sensors [2], and temperature stabilization [5] to reject the polarization field. In addition to a low and stable baseline, a practical system should have low measurement time and large sensing area to reduce biological variations [6].

[1]  B. Boser,et al.  A compact Hall-effect sensor array for the detection and imaging of single magnetic beads in biomedical assays , 2011, 2011 16th International Solid-State Sensors, Actuators and Microsystems Conference.

[2]  Boris Murmann,et al.  A 256 channel magnetoresistive biosensor microarray for quantitative proteomics , 2011, 2011 Symposium on VLSI Circuits - Digest of Technical Papers.

[3]  Gil U. Lee,et al.  A biosensor based on magnetoresistance technology. , 1998, Biosensors & bioelectronics.

[4]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[5]  Simone Gambini,et al.  Magnetic Relaxation Detector for Microbead Labels , 2012, IEEE Journal of Solid-State Circuits.

[6]  Hua Wang,et al.  A frequency-shift CMOS magnetic biosensor array with single-bead sensitivity and no external magnet , 2009, 2009 IEEE International Solid-State Circuits Conference - Digest of Technical Papers.

[7]  Mischa Megens,et al.  Integrated microfluidic bioprocessor for solid phase capture immunoassays. , 2011, Lab on a chip.

[8]  Bernhard E. Boser,et al.  A Mode-Matching ΔΣ Closed-Loop Vibratory-Gyroscope Readout Interface with a 0.004°/s/√Hz Noise Floor over a 50Hz Band , 2008, 2008 IEEE International Solid-State Circuits Conference - Digest of Technical Papers.

[9]  R. Dutton,et al.  Biological shot-noise and quantum-limited signal-to-noise ratio in affinity-based biosensors , 2005 .

[10]  B.E. Boser,et al.  A Mode-Matching $\Sigma\Delta$ Closed-Loop Vibratory Gyroscope Readout Interface With a 0.004$^{\circ}$ /s/$\surd{\hbox{Hz}}$ Noise Floor Over a 50 Hz Band , 2008, IEEE Journal of Solid-State Circuits.