detection of single red blood cell magnetic property using a highly sensitive gmr-sv biosensor...

Detection of Single Red Blood Cell Magnetic Property using a Highly Sensitive GMR-SV Biosensor

Sang-Suk Lee, Sang-Hyun ParkKwang-Suo Soh

2006.9.27 CKC Symposium

Contents

Magnetism and Sensitivity New Functional Soft Magnetic Materials Measurement and Resolution

Red Blood Cell Magnetophrosis Oxygen - RBC Magnetic Susceptibility Magnetophoretic Mobilities

Set up of Measurement System 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 )

Ferromagnetism : ( 0<P <1 )

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

Ferro-magnetis

m

Ferro-

1 ~ 105

Fe, Co, Ni, NiFe Gd, Dy, Er, Co-Pt

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

Diamagnetism None -10-5 ~ -10-7 Cu, Ti, W, Cr, O2

Mn, Pt, N2, Sn

Properties of GMR-SV Multilayers

Ta 5 nm

NiFe 4.0 nm

FeMn 7.0 nm

Ta 5 nm

NiFe 10 nm

Cu 2.6 nmNFM (Spacer)

FM (Free Layer)

AFM (Pinning Layer)

FM (Pinned Layer)

MR Ratio (Rap-Rp)/Rp = 4 ~ 9 %

Magneto sensitivity MR/H

Rap

RpRp

M-H curve

Sensing position

M-R curve

Hc

Application of GMR-SV Biosensor

PR(1.3 um)

SiO2(100 nm)

Contact pad (160 nm)

Silicon substrate

SV Sensor

Silica coated magnetic nanoparticles

•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

Advantage of GMR-SV Biosensor

Replace by RBC

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)

• Sensor size : 26 m2 • Output : 100 V , Resolution : 100 nT = 10-3 G M = 510-22 emu (erg/G) 5 10-2 B

Sensitivity of GMR/SV Biosensor

Tesla

Bio-magneto signal

ECGEEG

Mag

neti

c fi

eld

measu

rin

g lim

it

Cosmos Magnetic field Eart

h fi

eld

Electric Instrumentsaround field

General & Super-Conductor Magnet

PermanentMagnet

High VoltTransmitter,Transformer,Choke Coil,

Motor

Expectation of a Very High Sensitivity of GMR-SV

The Hemoglobin Properties

Of Red Blood Cell

* RBC : normal adult blood volume = 46 L average number = 45×106/cc circulatory lifetime = 120 days 1 RBC = 3×106 Hemoglobin 1 Hemoglobin = 4 Fe atoms

• Ferrous iron(Fe2+)

Fe2O3

• Binding Oxygen

Molecules

• 2-pair Polypetide Chain

Globin+4 Heme Group

• Ferric iron(Fe3+)

Fe3O4

• Loss of carrier power of oxygen and carbon dioxide

• Blue-green color

oxyhemoglobin deoxyhemoglobinmethemoglobin

Ligand & Light Absorption Hemoglobin and Fe

Paramagnetic Properties

Diamagnetic Properties

1. Capillary magnetophoresis of Human blood cells trapping in a flow system J. of Chromatography A, 2002

Apparatus Results

Red Blood Cell Magnetophoresis-1

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 concentr

ation 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 Magnetophoresis-2

Red Blood Cell Magnetic Susceptibilities

Red Blood Cell Magnetophoretic Mobilities

Ring Pattern by Liquid Drop Motion of Nano-particles

Before dropAfter drop :formation of ring pattern

Detection of Magnetic Nanoparticles

Change of Sensing Position by the abrupt Variation of Magnetic Field

Drop point

Before state : max & min signal

Output Sensing Signal Observation of Nanopartices

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 RBCand Biosensor

26 m2

Pure-RBC

Capillary and Approach to Biosenor

GMR-SV Biosensor

CapillaryRed Blood Cell →

Red Blood Cells←

Micro-capillary Movingand Manipulating Images

Needs and supplememts: Advanced Microscope, CCD Images, Uptaking RBC Techniques

Biological Cell Detection usingFerromagnetic Microbeads {by T. Bland’ Group}

Integrated microfluidic cell with multilayer ring sensors for single magnetic microbead detection {by T. Bland’ Group}

Future Research Plans

Fabrication of high sensitive GMR/SV biosensor Extraction of RBC or Heme-Sanal from Bo

nghan Duct

Nano-bio Lab.Sangji University

< Sept. 2006 Nov. 2007 >

BPL, SNU,CKC Research

< Dec. 2006 Feb. 2007 >

Investigation of single RBC’s and

Hemo-Sanal’s magneto-properties

< Dec. 2006 Feb. 2007 >

Fabrication of a highly sensitive GMR/SV biosensor with conetic film

Extraction of RBC or Hemo-Sanal from Bonghan Duct

Practical use of biosensor andmedical instruments

Set up measuring system,using micro-capillary and optical tweezer

To obtain an analytic value of bio-magnetic moleculessuch as : RBC, Hemo-Sanal, etc Using : (1) Micro-capillary controlling technology (2) Optical tweezer trapping and manipulation