LEGO Robotic DNA Sequencing

1
LEGO Robotic DNA Sequencing

• EDL Team E-18-C
• Bob Sherbert
• Christopher Young
• Armon Entezari
• Bryant Richardson
• Nick DiSciullo
• James Kim

2
Overview

• Problem/Backround
• DNA sequencing technologies and advances
• Miniaturization Problems/Impacts
• Designs
• Logistics
• Future Work

3
Human Genome Project

• Started in 1990, and was completed in 2003.
• Goals of Human Genome Project
• Determine the sequences of chemical base pairs
• Identify genes in human DNA
• Improve medical knowledge by relationships
  between genes and expressed traits
• What are they doing now?
• Working on in-depth analysis of complete
  chromosomes

4
Background/Problem / Rational

• Medical Benefits of DNA sequencing
• - Disease Testing and Possible Treatments
• Benefits offset by sample size

• http//admin.sun.ac.za/kie/unistel/medical_labs/sa
  mple.gif

5
Current Methods

• Sanger Method
• Uses Gel Electrophoresis
• Functions by making thousands of copies of a DNA
  strand, artificially terminating them at random
  intervals, separating them by mass in a gel cell,
  and using their dyed colors to determine the
  sequence in the cell
• Approx. 67,000 bases in one hour

http//www.6mgel.com/K2020_600.jpg
6
Current Methods

• Margulies, et al. Method
• Published in Nature 2005
• Uses a chip with millions of picoliter wells that
  react DNA fragments with known substrates
• Approx. 6.25 Million bases in one hour
• Other Recent Publications

Chart taken from E-18 Proposal
7
Recent Advances

• Korean scientists have built a tiny chip that
  copies DNA molecules very quickly
• It is approximately 4 times faster than PCR
• Coin size chip
• Potential component in portable medical
  diagnostic equipment

8
Simulation

• The Robotic Alternative
• Design a robot to sequence DNA faster and more
  accurately than previous methods.
• Test tube
• Lego Mindstorm NXT Simulation
• Macro-Level Design
• Balance becomes latching system

9
Nano-Scale Development

• EB Lithography
• Use of a focused beam of electrons to cut
  nano-sized patterns
• Up to 10nm wide lines can be made (Advantest)
• Nanoimprint Lithography
• Use of a mold with nano-structures being pressed
  against a thin resist cast
• 25nm wide lines with smooth and vertical
  sidewalls can be made (Nanonex)

www.nccr-nano.org/.../internet/ibm_xenon.jpg
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Nano-Scale Development (cont.)

• Photolithography
• Use of magnified light is passed through a mold
  of the desired structure and then focused onto a
  photo reactant surface

http//www.ece. gatech.edu/research /labs/vc/theor
y/ photolith.html
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Design 1

• Platform concept
• Struggles
• Height
• Parts

Design Rendering by Chris Young on ML Cad
12
Design 2

• Wheel Climbing upward
• Struggles
• Elastic Tension between wheels
• Base Size
• Rigidity

Design Rendering by Chris Young on ML Cad
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Design 3

• Linear motion
• Climbs upward
• Hardware
• Claws grasp center
• Circular motors convert circular motion to linear
• Struggles
• Insecure claws
• Gears
• Size and Sensor Placement

Photo taken by Chris Young
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Design 4

• Two claw linear climber
• Hardware
• Claws
• Envelopes DNA Strand
• Struggles
• Geometry of claws
• Linear translations
• Gear Mesh
• Available Parts

Photos taken by Chris Young
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Solution (Design 5)

• Hardware
• Enclosing Base
• Two Pincers
• Rubber Bands to Increase Closing Speeds
• Stabilizing Wheels

Photo taken by Chris Young
16
Solution (Design 5)

• Software
• Lego Mindstorms NXT
• Simple loop control
• Light sensor read/compare
• Hardwire transfer
• after data acquisition

Screen Shot of Code from Mindstorm Programming
NXT Software
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Costs

• Legos
• Kit
• 250
• Other Test Parts
• 40
• Rubber Bands
• Usually Break the Bank

• Real Nano-scale Robot
• Engineers Salarys
• 100,000 (18 week)
• Support Staff/Office
• 70,000
• Nano-fabrication equipment
• 6,000,000

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Environmental

• Lithography photoresist chemicals can be
  hazardous
• Unknown power source
• Lego battery disposal
• Release of nano-robots
• (http//www.lenntech.com/Periodic-chart-elements/S
  i-en.htm)

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Recommendations for future work.

• Power Source (nano-scale)
• On-board battery/Chemical interaction with Medium
• Wireless Transmission (nano-scale)
• Power consumptions
• Wave generations
• Multiple Robots
• Transcription/Translation Monitoring

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Summary

• Problem/Backround
• Sanger Method
• Miniaturization Problems/Impacts
• Balance and Lithography
• Designs
• Descending Inverted Crab
• Future Work
• Power Source and Wireless Transfer

21
Q A
22
References

• 1 H. Chan, Researchers Unravel DNA Tangles and
  Enzyme Seamstresses, dnaresearch, Mar. 23,
  2007. Online Available http//www.dnaresearch.
  com/2006/03/23/researchers-unravel-dna-tangles-and
  -enzyme-seamstresses/ Accessed Mar. 29, 2007.
• 2 Tiny Chip Copies DNA in a Flash,
  wiredscience, Apr 17, 2007. Online Available
  http//blog.wired.com/wiredscience/2007/04/tiny_de
  vice_cop.html Accessed Mar. 29, 2007.
• 3 Stories of discovery DNA research,
  mrc.ac.uk. Online Available
  http//www.mrc.ac.uk/YourHealth/StoriesDiscovery/D
  NAresearch/index.htm Accessed Apr. 2, 2007
• 4 T. Dixon. (2002). Approaches to Sequencing.
  University of Leeds/Royal Society of Chemistry.
  Online. Available http//www.chemsoc.org/Exempl
  arChem/entries/2002/proteomics/
• 5 H. Fields, (2005, 8 4) "Superfast DNA
  Sequencing." US News and World Report, Online.
  Available www.usnews.com
• 6 M. Margulies et al, "Genome Sequencing in
  Microfabricated High-Density Picolitre reactors."
  Nature, July 2005.