A GMR-based Magnetic Flow Cytometer Using Matched Filtering Chih-Cheng Huang, Xiahan Zhou, Da Ying, and Drew A. Hall University of California, San Diego
Optical Flow Cytometer • Quantitative cellular analysis in hematology • Identifying prognostic indicators: • Cancer, HIV, and other time-dependent biomarkers • Gold standard for multi-parametric analysis • Sophisticated instrumentation Challenge: Hard to translate to a PoC setting! 2
Magnetic Flow Cytometer Blood Signal [ m Ω ] MNPs Sample H z MNP-coated cells evoke change of sensor resistance 3
Optical- vs. Magnetic-FCM Optical FCM Magnetic FCM • Complex optics, lasers, and • Biological samples have no photodetectors magnetic background • Extensive sample preparation • Sample preparation can largely be eliminated • Long turnaround times and • Can be miniaturized, which out of reach for routine monitoring also improves their sensitivity 4
Multi-stripe Layout Single-strip Unique signature improves matched filtering 5
Magnetoresistive Sensors • Commonly used inside hard disk drives • Key enabler for higher areal density (larger HDD) • Nobel prize in 2007 awarded to Fert and Grünberg R.S. Gaster, D.A. Hall, S.X. Wang nanoLetters 2011 ( cover art ) 6
GMR Spin-Valves (GMR SV) H ext Antiparallel State Parallel State Bias Point (90˚) Antiparallel (180˚) Parallel (0˚) 𝑁𝑆 = 𝑆 𝐵𝑄 − 𝑆 𝑄 𝑆 𝑄 7 D.A. Hall, R.S. Gaster, et al. - Biosensors and Bioelectronics 2010
System Architecture Outlet Inlet 120µm 8
Micromagnetic Simulations Random distribution of MNPs on a cell 5,000× Adembeads Simulations closely match with our measurement results! 9
Hydrodynamic Analysis -8 -7 -6 -5 10 10 10 10 -8 -8 10 10 M450 -10 -10 10 10 MyOne -12 -12 M280 10 10 Adem -14 -14 10 10 Forces (N) Nanomag -16 -16 10 MACS 10 Magnetic force SHS30 DLVO force Gravity Hydrodynamic force -18 -18 10 10 Langevin force Magnetic force -20 -20 10 10 -22 -22 10 10 -8 -7 -6 -5 10 10 10 10 Particle diameter (m) 10
Micromagnetic Simulation of MNPs Y: signal ratio (R/R edge-peak ) (Height/Diameter) 11
ToF Measurement Results Detection of individual magnetic bead (M-450) 12
Matched Filtering Improve detection of signal events and reject false alarms Minimum detectable SNR:14 dB 4.5 dB 13
Flow Rate Optimization 120 40 100 Maximum Signal (m ) 30 80 Detected Events 60 20 40 10 20 0 0 0 10 20 30 40 50 0 10 20 30 40 50 Pumping rate ( L/min) Pumping rate ( L/min) Tradeoff between signal and flow rate for a given H z 14
Complex Detection MNPs Biotin-coated MNPs Polymer Beads 15
Measurement of Real Cells 20 μ m Detection of pancreatic cancer cells 16
Conclusion • Multi-stripe layout: enables distinct magnetic signature used for matched filtering • Matched filter: reduces minimum detectable SNR from 14 dB to 4.5 dB, and improves detection efficiency • ToF measurements: offers multi-parametric analysis of flowing analytes • GMR-based FCMs: increases portability and rapid “ sample-to-answer ” measurement capability 17
Thanks! 18
Recommend
More recommend
