molecular computation with automated microfluidic sensors (mcams) laura landweber * princeton...
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Molecular Computation with
Automated Microfluidic Sensors(MCAMS)
Laura Landweber*
Princeton University
Princeton UniversityL. L. Sohn†M. SinghA. SahaiR. Weiss
Stanford UniversityC. WebbR. Davis
UC BerkeleyA. P. Alivisatos
*DARPA Biocomp PI †NSF ITR PI
Molecular Computation with Automated Microfluidic Sensors Molecular Computation with Automated Microfluidic Sensors (MCAMS)(MCAMS)
Accelerate the field of molecular-based computing by increasing sensitivity and throughput and enabling “hands-free” molecular computation.
Combine microfluidic technology and biophysical methods for detecting nucleic acids with recently-developed algorithms of RNA-based computing to create a compact, automated, scalable, nucleotide-based computational device capable of rapidly and directly detecting the computational output.
New Ideas
Impact/Relevance
The sensing device•EBL on quartz is time consuming
•Etched samples have finite lifetimes- after ~5 msmts., too dirty to clean and reuse
•Solution: Embed pore in PDMS- make one master, cast from it forever…
•Seal PDMS to glass slip that holds electrodes
The master
•Negative pore: Electron-beam-defined polystyrene line (height, width adjustable 450 nm to <100 nm), or photolith defined etched quartz (1x1 m and bigger)
•Negative reservoirs: SU-8 photoresist (5 m thick)
Saleh and Sohn’s device in PDMS
AFM on PDMS shows successful casting down to 200 nm line width
Optical image of sealed devices
a small and quickly fabricated pore!
PDMS
Res
ervo
ir
Pore Reservoir
Measuring DNA
•Each downward spike=single DNA molecule
•Pore: diameter~300 nm, 4 m long
•Why does peak size vary? Varying DNA conformation?
Immobilization principle: surface enlargement with streptavidin coated beads, NHS-LC-biotin to aminolated silicon surface
silicon surfaceNHS-LC-biotin
streptavidin
Immobilization principle: surface enlargement with streptavidin coated beads, NHS-LC-biotin to aminolated silicon surface
biotinylated single DNA strands
silicon surfaceNHS-LC-biotin
streptavidin
Nanocrystal-labeled DNA
Alivisatos and Schultz , Nature 382 p. 609 1996; Angew. Chemie 38 p. 1808 1999related work by (Mirkin and Letsinger,) (Silvan and Braun)
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Scheduled Milestones/Success Metrics
Design prototype microfluidic system Identify methods for sizing and detection of RNA-based
computation outputs, such as electrical detection.Develop microfluidic chip to perform RNA-based computationExplore ways to make the chip versatile for different
computing algorithmsDesign microfluidic chip with reaction wells and switching valvesIdentify methods to detect 15-nt bits in RNA computationSolve an instance of a SAT problem using microfluidic device
Year 1 Year 2
Molecular Computation with
Automated Microfluidic Sensors
Princeton UniversityL. F. Landweber (15%)*L. L. Sohn (10%) †M. SinghA. Sahai (5%)R. WeissDanny van Noort (100%)Omar A. Saleh (30%)Zhao Huang (50%)
Stanford UniversityC. Webb (10%)R. Davis (1%)W. Tongparsit (50%)
UC BerkeleyA. P. Alivisatos (10%)Christine Micheel (40%)Teresa Pelelgrino (20%)
*DARPA Biocomp PI †NSF ITR PI
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