© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999

4.8.1 Cellular Topographics

Tactile topographic scanning provides the most direct means for examining cellular structures in vivo.^{484-486,2723-2727} For example, ex vivo live cell scanning in air by commercially available atomic force microscopy (AFM; Section 2.3.3) using a 20-40 nm radius tip allows nondestructive feature resolutions of ~50 nm across the top 10 nm of the cell. Investigators have used the scanning tip to punch a hole in the cell, then pull back and scan the breach, observing the membrane heal itself via self-assembly in real time. Up to ~KHz scanning frequencies are possible, with up to 1024 data points per scan line. The nanomechanical manipulator arm described in Section 9.3.1.4 achieves comparable tip velocities and positional accuracies.

Assuming a scan rate of ~10⁶ pixels/sec, a micron-scale nanodevice, once securely anchored (Section 9.4.3.3) to the surface of a (~20 micron)³ human cell, could employ a tactile scanning probe to image the 0.1% of plasma membrane lying within its (1.4 micron)² vicinity in ~2 sec to ~1 nm² resolution (~1 mm/sec tip velocity), or ~50 sec to ~0.2 nm (e.g., atomic) resolution (~0.2 mm/sec tip velocity). Inside the cell, and again post-anchoring, an entire 6 micron² mitochondrial surface could be imaged to atomic resolution in ~100 sec; the surface of a 100-nm length of 25-nm diameter microtubule could be atomically resolved in 0.2 sec -- though of course in a living cell these structures may be changing dynamically during the scanning process. From Eqn. 5.5, continuous power dissipation of a (0.1 micron)² scan head moving at 1 mm/sec through water is ~0.002 pW (~kT/pixel at ~10⁶ pixels/sec), though of course the energy cost of sensing, recording, and processing each pixel must be at least ~10 kT/pixel (ignoring the possibility of pre-computational image compression), so the total scanner power draw could be as high as 0.02-0.1 pW in continuous operation. Special scanning tips and techniques should allow topographic, roughness, elastic, adhesive, chemical, electrostatic (charge density), conductance, capacitance, magnetic, or thermal surface properties to be measured.

For large (~0.1-1 micron) cellular components, identification and preliminary diagnosis of improper structure may be possible using measured surface characteristics which may be matched to entries in an extensive onboard library, perhaps combined with dynamic monitoring of anomalies in cross-membrane molecular traffic using chemical nanosensors. Most membranes are self-sealing, so it should also be possible to gently insert a telescoping member into the target organelle (Section 9.4.5), which member then slowly reticulates and extrudes smaller probes with sensory tips in a fixed pattern and step size, allowing the acquisition of detailed internal structural and compositional information.

Small (~1-10 nm) protein-based components of the cell such as enzymes, MHC carriers, and ribosomes are self-assembling or require only modest assistance (e.g., molecular chaperones) to self-assemble. Reversible mechanical denaturation of these smaller proteins, using diamondoid probe structure to displace water molecules (thus reducing hydrophobic forces) and by using specialized handling tools akin to functionalized AFM tips and molecular clamps, may be followed by precise nondestructive amino acid sequencing (Chapter 20) to allow identification and diagnostic compositional analysis. Afterward, the protein molecule may be refolded back into its original minimum-energy conformation, possibly with the assistance of chaperone-like structures in some cases.³⁰⁴⁵

Last updated on 17 February 2003