Sang-Suk Lee, Sang-Hyun Park Kwang-Suo Soh

Detection of Single Red Blood Cell Magnetic
Property using a Highly Sensitive GMR-SV
Biosensor
Sang-Suk Lee, Sang-Hyun Park
Kwang-Suo Soh
2006.9.27 CKC Symposium
Contents

Magnetism and Sensitivity



Red Blood Cell Magnetophrosis




Oxygen - RBC
Magnetic Susceptibility
Magnetophoretic Mobilities
Set up of Measurement System



New Functional Soft Magnetic Materials
Measurement and Resolution
Micro Capillary Technology
Optical Tweezer Technology
Further Corporation Environment


Research Field of Prof. Tony Bland’s Group
Future Research Plans
Metals, Spin polarization (P),
and Magnetism
Metal : n() = n() ( P = (n()-n())/(n()+ n()) =0 )
( 0<P <1 )
Ferromagnetism :
Half Metals: CrO2, Fe3O4, PtMnSb ( P = 1)
3d
10-x
4f
14-x
Four general types of
a magnetism
Type
Magnetic moment
arrangement
Magnetic
Suscepibility
Substance
Fe, Co, Ni, NiFe
Gd, Dy, Er, Co-Pt
FerroFerromagnetism
1 ~ 105
Ferri-
Fe-O,
Ni-Zn, ferrite
Antiferromagnetism
0
NiO, MnO, Fe2O3
FeMn, IrMn, PtMn
Paramagnetism
10-7 ~ 10-3
Al, Ti, W, Cr, O2
Mn, Pt, N2, Sn
-10-5 ~ -10-7
Cu, Ti, W, Cr, O2
Mn, Pt, N2, Sn
Diamagnetism
None
Properties of GMR-SV
Multilayers
Ta 5 nm
Hc
NiFe 10 nm
FM (Free Layer)
NFM (Spacer)
Cu 2.6 nm
NiFe 4.0 nm
 M-H curve FeMn 7.0 nm
FM (Pinned Layer)
AFM (Pinning Layer)
Ta 5 nm
Rap
Sensing
position
Rp
Rp
 M-R curve
MR Ratio  (Rap-Rp)/Rp = 4 ~ 9 %
Magneto sensitivity  MR/H
Application of GMR-SV
Biosensor
Advantage of GMR-SV Biosensor
•The low requirement for sample amount
•Easy integration for multianalyte detection on a single chip
•Inexpensive and portable devices requiring little or no expertise
for their use
Silica coated magnetic
nanoparticles
Replace by RBC
PR(1.3 um)
SiO2(100 nm)
Contact pad
(160 nm)
SV Sensor
Silicon substrate
Highly Sensitive Magnetic
Films





Ni77Fe14Cu5Mo4
(Conetic film (Mu-metal))
Optimized condition : Hc = 0.055 Oe
Minimized purpose : ~0.055 Oe
(predicted values)
MS(MR/H) = 50 ~150 %/Oe
One of several hundreds for Hc of NiFe
Hc = 5~10 Oe
MS(MR/H) = 0.5 ~1.5 %/Oe
Measurement by using SQUID
 Sensitivity - nano tesla (10-9 T)
=> 10-5 Oe
 NiFe, NiFeCo => 10-2~10-3 Oe
 NiFeCuMo => 10-4~10-5 Oe
(theoretically 10-6)
Cosmos Magnetic field
Bio-magneto signal
EEG
ECG
Earth field
Magnetic field measuring limit
Expectation of a Very High
Sensitivity of GMR-SV
Electric Instruments
around field
High Volt
Transmitter,
General & SuperTransformer,
Conductor Magnet
Choke Coil,
Motor
Permanent
Magnet
Tesla
Sensitivity of GMR/SV Biosensor
• Sensor size : 26 m2
• Output : 100 V , Resolution : 100 nT = 10-3 G
M = 510-22 emu (erg/G)  5 10-2 B
The Hemoglobin Properties
Of Red Blood Cell
oxyhemoglobin
• Ferrous iron(Fe2+)
Fe2O3
• Binding Oxygen
Molecules
• 2-pair Polypetide Chain
Globin+4 Heme Group
deoxyhemoglobin
methemoglobin
• Ferric iron(Fe3+)
Fe3O4
• Loss of carrier power of
oxygen and carbon dioxide
• Blue-green color
* RBC : normal adult blood volume = 46 L
average number
= 45×106/cc
circulatory lifetime
= 120 days
1 RBC
= 3×106 Hemoglobin
1 Hemoglobin
= 4 Fe atoms
Ligand & Light Absorption
Hemoglobin and Fe
 Diamagnetic Properties
 Paramagnetic Properties
Red Blood Cell
Magnetophoresis-1
1. Capillary magnetophoresis of Human blood cells
trapping in a flow system J. of Chromatography A, 2002
Apparatus
Results
Red Blood Cell
Magnetophoresis-2
2. Red Blood Cell Magnetophrosis
Maciej Zborowski et al, Biophysical Journal 84, 2638 (2003)
1) The measured magnetic moments of hemoglobin :
its compounds on the relatively high hemoglobin
concentration of human erythrocytes
2) Differential migration of these cells was possible
if exposed to a high magnetic field (1.40 T).
3) Development of a new technology, cell tracking
velocimetry (CTV) the migration velocity of oxy-,
deoxy-, and metHb-containing erythrocytes
Red Blood Cell
Magnetic Susceptibilities
Red Blood Cell
Magnetophoretic Mobilities
Detection of Magnetic
Nanoparticles
Ring Pattern by Liquid Drop Motion of Nano-particles
Before drop
After drop :
formation of
ring pattern
Output Sensing Signal
Observation of Nanopartices
Change of Sensing Position by the abrupt Variation of Magnetic Field
Drop point
Before state : max & min signal
Capillary Capture
Red Blood Cell
Biophysics of cell membranes :
Investigation of the changes in the mechanical and
rheological properties of blood cells in diabetes
Taken by http://newton.ex.ac.uk/research/biomedical/membranes/
Optical Trapping and Manipulation
of Single Cells using Infrared
Laser Beams
Set up of System-1
Set up of System-2
Micro-hole Capillary with RBC
and Biosensor
Pure-RBC
26 m2
Capillary and Approach
to Biosenor
GMR-SV Biosensor
Capillary Red Blood Cell
→
Red Blood Cells
←
Micro-capillary Moving
and Manipulating Images
Needs and supplememts:
Advanced Microscope, CCD Images, Uptaking RBC Techniques
Biological Cell Detection using
Ferromagnetic Microbeads {by T. Bland’ Group}
Integrated microfluidic cell with multilayer
ring sensors for single magnetic microbead
detection {by T. Bland’ Group}
Future Research Plans
To obtain an analytic value of bio-magnetic molecules
such as : RBC, Hemo-Sanal, etc
Using : (1) Micro-capillary controlling technology
(2) Optical tweezer trapping and manipulation
Fabrication of
sensitive
Fabrication
ofhigh
a highly
GMR/SV biosensor
sensitive GMR/SV biosensor
with conetic film
Nano-bio Lab.
Sangji University
< Sept. 2006
 Nov. 2007 >
Practical use of
biosensor and
medical instruments
of RBC or
ExtractionExtraction
of RBC or Heme-Sanal
Hemo-Sanal
from
from Bonghan
Duct
Investigation of
single RBC’s and
Hemo-Sanal’s
magneto-properties
< Dec. 2006
 Feb. 2007 >
Bonghan Duct
BPL, SNU,
CKC Research
< Dec. 2006
 Feb. 2007 >
Set up measuring system,
using micro-capillary and
optical tweezer