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: CrO 2, Fe 3 O 4, PtMnSb ( P = 1) 3d 10-x 4f 14-x

4. Four general types of a magnetism TypeMagnetic moment arrangement Magnetic Suscepibility Substance Ferro- magnetism Ferro- 1 ~ 10 5 Fe, Co, Ni, NiFe Gd, Dy, Er, Co-Pt Ferri- Fe-O, Ni-Zn, ferrite Antiferromagnetism 0 NiO, MnO,  Fe 2 O 3 FeMn, IrMn, PtMn Paramagnetism 10 -7 ~ 10 -3 Al, Ti, W, Cr, O 2 Mn, Pt, N 2, Sn DiamagnetismNone -10 -5 ~ -10 -7 Cu, Ti, W, Cr, O 2 Mn, Pt, N 2, Sn

5. 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 nm NFM (Spacer) FM (Free Layer) AFM (Pinning Layer) FM (Pinned Layer) MR Ratio  (R ap -R p )/R p = 4 ~ 9 % Magneto sensitivity   MR/  H R ap RpRp RpRp  M-H curve Sensing position  M-R curve HcHc

6. Application of GMR-SV Biosensor PR(1.3 um) SiO 2 (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

7. Highly Sensitive Magnetic Films Ni 77 Fe 14 Cu 5 Mo 4 (Conetic film (Mu-metal)) Optimized condition : H c = 0.055 Oe Minimized purpose : ~0.055 Oe (predicted values) MS(  MR/  H) = 50 ~150 %/Oe One of several hundreds for H c of NiFe H c = 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. Sensor size : 2  6  m 2 Output : 100  V, Resolution : 100 nT = 10 -3 G M = 5  10 -22 emu (erg/G)  5  10 -2  B Sensitivity of GMR/SV Biosensor Tesla Bio-magneto signal ECG EEG Magnetic field measuring limit Cosmos Magnetic field Earth field Electric Instruments around field General & Super- Conductor Magnet Permanent Magnet High Volt Transmitter, Transformer, Choke Coil, Motor Expectation of a Very High Sensitivity of GMR-SV

9. The Hemoglobin Properties Of Red Blood Cell * RBC : normal adult blood volume = 4  6 L average number = 4  5×10 6 /cc circulatory lifetime = 120 days 1 RBC = 3×10 6 Hemoglobin 1 Hemoglobin = 4 Fe atoms Ferrous iron(Fe 2+ ) Fe 2 O 3 Binding Oxygen Molecules 2-pair Polypetide Chain Globin+4 Heme Group Ferric iron(Fe 3+ ) Fe 3 O 4 Loss of carrier power of oxygen and carbon dioxide Blue-green color oxyhemoglobin deoxyhemoglobin methemoglobin

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

11. 1. Capillary magnetophoresis of Human blood cells trapping in a flow system J. of Chromatography A, 2002 ApparatusResults Red Blood Cell Magnetophoresis-1

12. 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 Magnetophoresis-2

13. Red Blood Cell Magnetic Susceptibilities

14. Red Blood Cell Magnetophoretic Mobilities

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

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

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 h ttp://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 2  6  m 2 Pure-RBC

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

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 Fabrication of high sensitive GMR/SV biosensor Extraction of RBC or Heme-Sanal from Bonghan 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 and medical instruments Set up measuring system, using micro-capillary and optical tweezer 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