1. Scanning Probe Microscopy
and Nanotechnology for
Biomedical Applications
M. Dudziak
Silicon Dominion / IEPB
May 6, 1999

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. 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. 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. 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. 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. 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. 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. Set 3 of Overhead Slides
• Neural and Epithelial AFM Images

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. Sets 4 & 5 of Overhead Slides
• Fractal/Chaos/QB overview
• Soliton equations and graphs

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. 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. Path.HTM and Pivot.HTM
• Work by N. Thomas (UK)

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. Set 6 of Overhead Slides
• Computer simulations of quaternion Julia sets by
Tim Stilson

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. 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)