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

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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!

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Magnetic Flow Cytometer

Signal [mΩ]Blood

SampleMNPs

MNP-coated cells evoke change of sensor resistance

Hz

Optical FCM

• Complex optics, lasers, and

photodetectors

• Extensive sample preparation

• Long turnaround times and

out of reach for routine

monitoring

Magnetic FCM

• Biological samples have no

magnetic background

• Sample preparation can

largely be eliminated

• Can be miniaturized, which

also improves their sensitivity

Optical- vs. Magnetic-FCM

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Multi-stripe Layout

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Single-strip

Unique signature improves matched filtering

• Commonly used inside hard disk drives

• Key enabler for higher areal density (larger HDD)

• Nobel prize in 2007 awarded to Fert and Grünberg

Magnetoresistive Sensors

6

R.S. Gaster, D.A. Hall, S.X. Wang

nanoLetters 2011 (cover art)

Parallel State

GMR Spin-Valves (GMR SV)

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Bias Point (90˚)

𝑀𝑅 =𝑅𝐴𝑃 − 𝑅𝑃

𝑅𝑃

Parallel (0˚)

Antiparallel (180˚)

D.A. Hall, R.S. Gaster, et al. - Biosensors and Bioelectronics 2010

Hext

Antiparallel State

System Architecture

8

Inlet

Outlet

120µm

Micromagnetic Simulations

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5,000× Adembeads

Simulations closely match with our measurement results!

Random distribution of

MNPs on a cell

Hydrodynamic Analysis

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10-8

10-7

10-6

10-5

10-22

10-20

10-18

10-16

10-14

10-12

10-10

10-810

-810

-710

-610

-5

Magnetic force

DLVO force

Gravity

Hydrodynamic force

Langevin force

Magnetic force

Particle diameter (m)

Fo

rce

s (

N)

10-22

10-20

10-18

10-16

10-14

10-12

10-10

10-8

M450

M280MyOne

Adem

Nanomag

SHS30MACS

Micromagnetic Simulation of MNPs

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Y: signal ratio (R/Redge-peak)

(Height/Diameter)

ToF Measurement Results

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Detection of individual magnetic bead (M-450)

Matched Filtering

13

Improve detection of signal events and reject false alarms

Minimum detectable SNR:14 dB 4.5 dB

Flow Rate Optimization

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0 10 20 30 40 500

10

20

30

40

De

tecte

d E

ve

nts

Pumping rate (L/min)

0 10 20 30 40 500

20

40

60

80

100

120

Ma

xim

um

Sig

na

l (m

)

Pumping rate (L/min)

Tradeoff between signal and flow rate for a given Hz

Complex Detection

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MNPs

MNPsBiotin-coated

Polymer Beads

Measurement of Real Cells

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Detection of pancreatic cancer cells

20μm

• 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

Conclusion

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Thanks!

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