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  1. 1. Scanning Probe Microscopy and Nanotechnology for Biomedical Applications M. Dudziak Silicon Dominion / IEPB May 6, 1999
  2. 2. Contents♦ What is SPM and why use it in medicine? – AFM, STM, LFM, MFM♦ Some applications and results in life sciences & biomaterials research♦ Approaches and methods - – in vitro // fixed – biological // inorganic♦ Using adaptive learning algorithms and pattern recognition for control and interpretation
  3. 3. Basics of SPM• Surface forces - Van der Waals, EMF, quantum tunneling• Tip/cantilever movement/current signal• A/D translation of surface reading --> 3D image• Alternative to EM• Partner technology for Optical, Confocal, Near-field Optical Microscopy• Imaging PLUS lithography/fabrication
  4. 4. SPM Technology : 35mm Slides (S) and Overhead Slides (O)• SPM rationale (S)• EM comparisons (S)• STM current/height modes, resolution (S)• AFM principles, types (S, O)• Other Modes (S)• Instrument variation and nonlinearities (S)• Different sample types and images (S)• Sets 0, 1, 2
  5. 5. Research Application Using SPM• Investigation of quantum field effects (QFT) and bioelectromagnetics upon cell topology, structural dynamics, growth• Fundamentally a mathematical, geometrical approach to questions of differentiation and communication• Emphasis upon cytoskeletal and membrane topological features• Search to measure (bio)solitons, fractal & p-adic & chaotic measurables
  6. 6. Foundations• Solitons - stable nonlinear waves• Biosolitons in protein (MT, actin)• Dynamics of MT and IF and effects from EMF, Ca+, other gradients• Intriguing possibilities of the “CA” effect : – neighbors, boundaries, population types• How to study? – Theory and modeling – Computer-based simulation – Experimentation (AFM, confocal, MODE)
  7. 7. Experimentation Goals, Requirements• Living cells• Controlled culture growth• Mechanisms for reproducible sample preparation, gradient application, observation techniques• AFM and AFM+Optical+Confocal best way to go• Main accomplishments (to date): – achieved relative stability in imaging – design of testbed – migration path of image data to modeling/analysis
  8. 8. Neural and Epithelial Imaging• Digital Instruments Nanoscope-III• XR1 Xenepus retinal ganglial cell line• L15 media + embryo extract and fetal calf serum• Relatively rapid death during and after imaging• Multiple rinsing + moisture bath• Bioscope much better than simple fluid cell• Typical XY scan 50 µm x 50 µm• Typical Z scale 2 µm
  9. 9. Set 3 of Overhead Slides• Neural and Epithelial AFM Images
  10. 10. Interpretation, Hypotheses and Theory• Fractal and Chaos Dimensions• Prior interesting observables in large-scale biology (organisms, organs, metabolic rate)• MT structure variations in different pathologies, esp. oncological• Soliton modeling (Dubna, Novosibirsk, ‘93-’96)
  11. 11. Sets 4 & 5 of Overhead Slides• Fractal/Chaos/QB overview• Soliton equations and graphs
  12. 12. Conceptual Formulation• Massive large-scale parallel simulated-annealing type computation in phospholipid membranes – Giving rise to• Soliton-like propagations – Converging to modulation of ion channels and• Amplified effects (QP “pilot wave” principle) in cytoskeletal topology• Effecting changes in cell motility, 3D geometry, and cytoplasmic movement of intracellular components – Giving rise to• Changes in inter-cellular membrane signaling and• Intracellular metabolism and reproduction control
  13. 13. A Geometrical Excursion• Projective Geometry (Pappus, Pascal, Desargues, Klein, Veblen)• Metamorphosis of biological form types from a confluence of simple projections• Path curves, pivot transforms, vortices, and buds• Not magic, just numbers
  14. 14. Path.HTM and Pivot.HTM• Work by N. Thomas (UK)
  15. 15. “Hamilton’s Birds of Prey”• A rare and untamable species• Never photographed in the wild• Sensitive to the touch• Easily camouflaged• Giving rise to speculation about the nature of Geometry and Evolution• Known to inhabit large silicon-based forests
  16. 16. Set 6 of Overhead Slides• Computer simulations of quaternion Julia sets by Tim Stilson
  17. 17. Acknowledgements• Basil Hiley, David Bohm, David Finkelstein• Robert Rosen, Valery Sanyuk, Louis Kaufmann• Hiroomi Umezawa, Karl Pribram, Peter Kugler• Matti Pitkanen, Nick Thomas• Eric Henderson, Tim Stilson• Digital Instruments, Park Scientific Instruments• Many students and assistants• NSF, Jeffress Foundation
  18. 18. References and More• Web resources on SPM: – Start with Digital, Park, Rice, JHU, NCSU, IowaSU• Web Resources on MathBio, QB, BioEM: – Principia Cybernetica and links therefrom• Request from MJD and you may receive, eventually• Explore www.silicond.com/library (No librarian or secretary --- self-service)