Nanomedicine, Volume I: Basic Capabilities
© 1999 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999
126.96.36.199 Morcellation and Mincing
Morcellation is the fragmentation of biological materials as they are excised from the body; mincing is the progressive reduction in size of tissue segments by mechanical means. Chunks of biological material may be excised from the body using a tool such as the core sampler described in Section 9.3.2 (3). Cutting is required because many connective tissues have strengths on the order of 10-100 atm but the body is only pressurized to ~1 atm, so vacuum suction alone is insufficient to pull coherent tissues apart.
In the simplest design, morcellated material is passed through successive banks of fixed diamondoid cutting blades or rotating diamondoid cutting disks positioned at various angles with progressively more closely-spaced blade edges. The target material is minced into nanometer-sized bits. Each blade is geared for maximum force application at relatively slow speed and turns in a tightly fitted sleeve, providing an automatic self-cleaning action. More complex designs might include paddlewheeling-bucket or orthogonal-blade arrays whose interiors are cleared by pistons after completion of the mincing action on material compacted into the cutting chamber by a larger piston. Table 9.3 shows that diamond and other potential blade materials are far stronger than all forms of biological matter, including dental enamel which is the hardest natural substance found in the human body.
To quantify the mincing action, consider a blade of length Lblade, cutting edge width Wedge, and compressive strength Tblade (N/m2) which applies a force Fblade to a biological sample of length Lsample and thickness xsample and tearing strength Tsample. Assuming Lblade = Lsample, then the minimum force required to cut the sample is Fmin = Tsample Lblade Wedge < Fblade, the chopping energy per full blade stroke is Estroke = Fblade xsample, and the continuous power requirement of the blade (neglecting drag during the return stroke) is Pblade = Estroke nblade where nblade is chopping frequency in Hz. Taking Lblade = 1 micron, Wedge = 1 nm, xsample = 1 micron, Tsample = 108 N/m2, and nblade = 1 KHz, then Fmin = 100 nN, Estroke = 0.1 pJ, and Pblade = 100 pW.
Consider next an ideal morcellation system which accepts a cubic biological sample of volume Vsample = Lsample3 and minces it by progressive halving into final pieces of volume Vminced = Lminced3 in a minimum number of Ncut = log2 (Vsample / Vminced) cuts (analogous to "oct-trees" in computer science3155). The energy required to make the ith cut is Tsample Wedge [Vsample / 2(i-1)]2/3 and after the ith cut there are 2i intermediate pieces, hence the total energy Eminced required to make all cuts down to the final pieces is:
The minimum size of the final pieces depends on the character of the sample material, the edge sharpness and speed of the blades, and numerous other factors, but in most cases cannot be smaller than 1-10 nm -- natural biomolecules like hemoglobin, insulin, or albumin are 5-10 nm in diameter (Fig. 3.15). A crude limit is Estroke >~ Ebond, where Ebond = 180-1800 zJ for individual covalent bonds (Section 3.5.1), which implies a minimum final piece size of Lmin ~ (Ebond/Tsample Wedge)1/2 assuming Lblade = xsample = Lmin. Taking Ebond ~ 1000 zJ, Tsample = 108 N/m2 and Wedge = 1 nm, then Lmin ~ 3.2 nm.
Eqn. 9.54 may now be applied to a specific morcellator configuration. Taking Vsample = 1 micron3, Vminced = 1000 nm3 (Lminced = 10 nm), Wedge = 1 nm, Tsample = 108 N/m2, and nblade = 1 KHz, then Ncut = 20 cuts, blade velocity vblade = nblade Vsample1/3 = 1 mm/sec, total mincing time tminced = Ncut / nblade = 20 millisec, volume mincing rate 'Vminced = Vsample / tminced = 50 micron3/sec, total energy to mince a single sample of volume Vsample is Eminced = 40 pJ, and continuous power dissipation while the morcellator is in operation is Pminced = Eminced / tminced = 2000 pW. Care must be taken to minimize sample adhesion in blade surface design (Section 9.2.3).*
* M. Krummenacker notes that mechanical bond cutting might leave behind reactive fragments, possibly including radicals, that could dehydrogenate the diamond blade surface via radical abstraction, leading to chemomechanical blade wear. A fluorine-passivated diamond blade might be more resistant to such wear, and hydrogen bonding with fluorine increases protein-diamond friction, possibly giving better cutting.
Once reduced to multi-nanometer-scale chunks, biological refuse may be disposed of directly (Chapter 16) or may be further digested using inorganic acids, lysosomal enzymes (Sections 188.8.131.52 and 10.4.2), collagenases,359 artificial enzymes, or even direct molecular mechanodecomposition (Section 184.108.40.206.5) which is the inverse of mechanosynthesis. A discussion of the biocompatibility of minced tissue and methods of final disposal is deferred to Chapters 15 and 16.
Last updated on 21 February 2003