Proceedings Article | 17 April 2006
KEYWORDS: Microfluidics, Artificial intelligence, Genetics, Nanorobotics, Control systems, Stem cells, Atomic force microscopy, In vitro testing, Biology, Organisms
To investigate Somatic Cell Nuclear Transfer (SCNT), we choose the Drosophila cloning based on a recent experiment
(Haigh, MacDonald, Lioyd, Gen. V.169,1165, 2005) to be improving the adulthood rate in 2-week turn-around time.
Original 1% success rate might be due to three less certain key steps: (i) The double membranes of a nucleus has at its
pore led to the attached Rough Endoplasmic Reticulum (ER), passing the genetic instruction to assemble amino acids,
proteins and lipid at its smooth end. Also, any mismatch of nucleus with mitochondria (MT) having own small genome
for energy production had led to reprogramming failure. (D. Wallace, UC Irvine, Nature,Vol. 439, pp.653). We ask
"whether a guest DNA shall come with its servants, ER, MT, etc or not." It seemed to be logical to have a whole
package replaced the embryonic host cell, equipped with all housekeeping, energy production and mitosis
functionalities except the genetic information. To answer this hypothesis, we design a bio-NanoRobot having a surgical
precision in removing the desired nucleus with or without its attached ER and MT material. The design is based on a
real-time multiplexing principle of combining both the soft-contact-vision of the Nobel Laureate Binning called Atomic
Force Microscope (AFM) and the hard-grasp-action called NanoRobotTM by Xi and Szu, 2004. However, applying it,
we must re-design a new bio-NanoRobot, consisting of two parts: (a) multiple resolution analysis (MRA) using AI to
control a dual-resolution vision system: the soft-contact-vision AFM co-registered with a on-contact high resolution
imaging; and (b) two cantilever arms capable to hold and enucleate a cell. The calibration and automation are controlled
by AI Case-Based reasoning (CBR) together with AI Blackboard (BB) of the taxonomy, necessary for integrating
different tool's tolerance and resolution at the same location. Moreover, keeping the biological sample in one place,
while a set of tools rotates upon it similar to a set of microscopic lenses, we can avoid the non-real-time re-imaging, and
inadvertent contamination. Applying an imposing electrical field, we can take the advantage of structure differences in
smooth nuclear membranes inducing Van der Waal's forces versus random cytoplasm. (ii) The re-programming of
transplanted cells to the ground state is unclear and usually relies on electrochemical means tested systematically in a
modified 3D Caltech micro-fluidics. (iii) Our real-time MRA video-manipulator can elucidate the mitosis's tread-mill
assembly mechanism in the development course of pluripotent stem cell differentiation into specialized tissue cell
engineering. Such a combination bio-NanoRobot and micro-fluidic massive parallel assembly-line approach might not
only replace the aspirating pipette with a self- enucleating Drosophila embryonic eggs, but also genetically reproduce a
large amount of cloning embryonic eggs repeatedly for various re-programming hypotheses.