Detection of Single Red Blood Cell Magnetic Property

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 n Magnetism and Sensitivity ¡ ¡ n Red Blood Cell Magnetophrosis ¡ ¡ ¡ n Oxygen - RBC Magnetic Susceptibility Magnetophoretic Mobilities Set up of Measurement System ¡ ¡ n 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: Cr. O 2, Fe 3 O 4, Pt. Mn. Sb ( P = 1) 3 d 10 -x 4 f 14 -x

Four general types of a magnetism Type Magnetic moment arrangement Magnetic Suscepibility Substance Fe, Co, Ni. Fe Gd, Dy, Er, Co-Pt Ferromagnetism 1 ~ 105 Ferri- Fe-O, Ni-Zn, ferrite Antiferromagnetism 0 Ni. O, Mn. O, Fe 2 O 3 Fe. Mn, Ir. Mn, Pt. Mn Paramagnetism 10 -7 ~ 10 -3 Al, Ti, W, Cr, O 2 Mn, Pt, N 2, Sn -10 -5 ~ -10 -7 Cu, Ti, W, Cr, O 2 Mn, Pt, N 2, Sn Diamagnetism None

Properties of GMR-SV Multilayers Ta 5 nm Hc Ni. Fe 10 nm Cu 2. 6 nm Ni. Fe 4. 0 nm v M-H curve Fe. Mn 7. 0 nm FM (Free Layer) NFM (Spacer) FM (Pinned Layer) AFM (Pinning Layer) Ta 5 nm Rap Sensing position Rp Rp v 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) Si. O 2(100 nm) Contact pad (160 nm) SV Sensor Silicon substrate

Highly Sensitive Magnetic Films n n n Ni 77 Fe 14 Cu 5 Mo 4 (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 Ni. Fe 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 ¡ Ni. Fe, Ni. Fe. Co => 10 -2~10 -3 Oe ¡ Ni. Fe. Cu. Mo => 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 & Super. Transformer, Conductor Magnet Choke Coil, Motor Permanent Magnet Tesla Sensitivity of GMR/SV Biosensor • Sensor size : 2 6 m 2 • Output : 100 V , Resolution : 100 n. T = 10 -3 G M = 5 10 -22 emu (erg/G) 5 10 -2 B

The Hemoglobin Properties Of Red Blood Cell oxyhemoglobin • Ferrous iron(Fe 2+) Fe 2 O 3 • Binding Oxygen Molecules • 2 -pair Polypetide Chain Globin+4 Heme Group deoxyhemoglobin methemoglobin • Ferric iron(Fe 3+) Fe 3 O 4 • 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 met. Hb-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

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 m 2

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 a highly sensitive Fabricationof high sensitive GMR/SV biosensor with conetic film Nano-bio Lab. Sangji University < Sept. 2006 Nov. 2007 > Practical use of biosensor and medical instruments Extraction of RBCfrom of RBC or Heme-Sanal or Hemo-Sanal from Bonghan Duct Investigation of single RBC’s and Hemo-Sanal’s magnetoproperties < Dec. 2006 Feb. 2007 > Duct BPL, SNU, CKC Research < Dec. 2006 Feb. 2007 > Set up measuring system, using micro-capillary and optical tweezer