1. DNA Computing and Robotics:
Engineering (Science?), Fun, and Applications
Milan N. Stojanovic
NSF Center for Molecular Cybernetics
Department of Medicine
Columbia University

2. Suppose we have a set of primitives:
Sensor primitives:
Computing primitives:
Moving primitives:

3. Recipe for Computing Primitives:
Beacons (Tyagi and Kramer)
1. Take Recognition Regions,
2. Take Nucleic acid catalysts,
Phosphodiesterase (Joyce) E S
Ligase (Szostak) E S1 S2
3. And combine (for computing elements, at least) them in:
Cf. modular design (e.g. Breaker…)

4. Logic Gates: YES (Detector or Sensor Gate)
50000
100000
150000
200000
250000
100
200
300
400
t (min) FU
Stojanovic et al., ChemBioChem 2001
Stojanovic et al., J. Am. Chem. Soc. 2002
Joyce 1995, Breaker 1999, Tyagi, Kramer 1996

5. Switching Primitives (Logic Gates):
NOT
AND
Three-input Gates

6. Some demonstrations of molecular computing:
A. Full adder (Lederman et. al, Biochem. 2006)
B. Maya-II (Macdonald et al. Nano Lett. 2006)
11 × 01 =
11 × 10 =
11 × 11 =
(3×1=3)
(3×2=6)
(3×3=9)
01 × 01 =
(1×1=1)
01 × 10 =
(1×2=2)
C. DNA Calculator (Macdonald)
D. AND Hub with Beads (Rudchenko)
(Yashin et al. JACS ~2007)

7. Implementation of Naughts-and-Crosses Playing Algorithm with Deoxiribozymes: Molecular Array of YES and ANDANDNOT Gates (MAYA)
Stojanovic, Stefanovic, Nat. Biotech. 2003

8. MAYA vs. Milan: Losing Game

9. The Simplest Moving Primitive:

10. But, what about multivalent design?
Pei et. al JACS, 2006

11. AFM Images of Spider at Starting Point
Kyle Lund, Hao Yan, video now: with Nadine Dabby, Erik Winfree

12. AFM images of Spider on Lanes of Substrates
Kyle Lund, Hao Yan
Video with: Nadine Dabby, Erik Winfree

13. Center for Molecular Cybernetics Phase II?

14. Center Members & Friends
Erik Winfree (CS)
Hao Yan (CHE)
Niles Pierce (ApM)
Paul Krapivsky (Phys)
Sergei Rudchenko (BPh)
Nils Walter (CHE)
Milan Mrksich (CHE)
Darko Stefanovic (CS/EE)
Milan Stojanovic (MEDSci)
Nadrian Seeman (CHE)
Henry Hess (CHE/MATS)
William Shih (CHE)
Srboljub Mijailovich (ME)
Natasha Yonoska (MATH)
Satoshi Murata (CS/ME)
Friedrich Simmel (P-CHE)
Vojislav Stojkovic (CS)
Qiao Lin (ME)
Paul Rothemund (CHE/CS)
CHE
CHE
Chemical Bonding Center NSF (CHE )

15. Acknowledgments:
Postdocs: Steven Taylor, Renjun Pei, Dmitry Kolpashchikov, Joanne Macdonald
Tech’s: Stanka Semova, Erik Green, Payal Pallavi, Ma Li
High Shool Program: Harvey Lederman, Yang Lee, Marko Sutovic, Kiran Pendri, Wengho Lu, Kirill Lebedov, Srikanth Damera, George Lederman, Kaitlin Kyi.
Tiffany Elizabeth Mitchell
Collaborators:
Sergei Rudchenko (HSS), Ruslan Yashin
Darko Stefanovic (UNM), Mark Olah
Nils Walter (UM, Ann Arbor), Tony Manzo, Chamaree De Silva
Vincent Butler (Columbia)
Milan Mrksich (Chicago), Haim Tsubery
Erik Winfree (Caltech), Georg Seelig, Nadine Dabby
Hao Yan (ASU), Kyle Lund
Current funding NSF (ITR, 3xEMT, and CBC), JDRF, NIH (NCI-R21)
Lymphoma and Leukemia Society Scholarship
Previously: NASA, NSF QuBIC, NSF Biophotonics, NIH (NIBIB), Searle

16. Potential practical applications:
1. Cell-death by Boolean Calculations:
2. Glucose-triggered movement of catalytic nanoassemblies: