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

1. 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

2. 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

3. 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

4. Four general types of a magnetism

5. Properties of GMR-SV Multilayers Ta 5 nm Hc FM (Free Layer) NiFe 10 nm NFM (Spacer) Cu 2.6 nm FM (Pinned Layer) NiFe 4.0 nm AFM (Pinning Layer) • M-H curve FeMn 7.0 nm Ta 5 nm Rap Sensing position Rp Rp • M-R curve MR Ratio  (Rap-Rp)/Rp = 4 ~ 9 % Magneto sensitivity MR/H

6. 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 Application of GMR-SV Biosensor Silica coated magnetic nanoparticles Replace by RBC PR(1.3 um) SiO2(100 nm) Contact pad (160 nm) SV Sensor Silicon substrate

7. 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)

8. Expectation of a Very High Sensitivity of GMR-SV Earth field Electric Instruments around field Cosmos Magnetic field High Volt Transmitter, Transformer, Choke Coil, Motor Bio-magneto signal General & Super- Conductor Magnet Magnetic field measuring limit EEG ECG 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

9. The Hemoglobin Properties Of Red Blood Cell deoxyhemoglobin methemoglobin oxyhemoglobin • 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 * 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

10. Ligand & Light Absorption Hemoglobin and Fe  Diamagnetic Properties  Paramagnetic Properties

11. Red Blood Cell Magnetophoresis-1 1.Capillary magnetophoresis of Human blood cells trapping in a flow systemJ. of Chromatography A, 2002 Apparatus Results

12. Red Blood Cell Magnetophoresis-2 2. Red Blood Cell Magnetophrosis Maciej Zborowski et al, Biophysical Journal 84, 2638 (2003) • 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

13. Red Blood Cell Magnetic Susceptibilities

14. Red Blood Cell Magnetophoretic Mobilities

15. Detection of Magnetic Nanoparticles Ring Pattern by Liquid Drop Motion of Nano-particles Before drop After drop : formation of ring pattern

16. Output Sensing Signal Observation of Nanopartices Change of Sensing Position by the abrupt Variationof Magnetic Field Drop point Before state : max & min signal

17. 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/

18. Optical Trapping and Manipulation of Single Cells using Infrared Laser Beams

19. Set up of System-1

20. Set up of System-2

21. Micro-hole Capillary with RBC and Biosensor Pure-RBC 26 m2

22. Capillary and Approach to Biosenor GMR-SV Biosensor Red Blood Cells ← Capillary Red Blood Cell →

23. Micro-capillary Moving and Manipulating Images Needs and supplememts: Advanced Microscope, CCD Images, Uptaking RBC Techniques

24. Biological Cell Detection using Ferromagnetic Microbeads {by T. Bland’ Group}

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

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