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Molecular Sensing Using Nanofluidics. A Novel solution using Nanofluidic Field Effect Transistors By Laura Benson, Chris Hughes, and Zac Milne. The Need. 2009 NIH challenge for scientists to learn to sequence DNA for less than $1000
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Molecular Sensing Using Nanofluidics A Novel solution using Nanofluidic Field Effect Transistors By Laura Benson, Chris Hughes, and Zac Milne
The Need • 2009 NIH challenge for scientists to learn to sequence DNA for less than $1000 • With cheap and quick access to a patients genetic information, doctors will be able to usher in a new level of personalized medicine • Ineffective treatments can be avoided and better drugs can be developed
The current leader • The leading technology to achieve this goal is a Nanopore based Coulter Counter • Coulter counters have been around for more than 50 years, and are used to count cells based on a change in current as they pass through a pore • As each nucleobase of DNA passes through the pore, each alters the current in a different way, thus allowing for sequencing
Nanofluidic Field Effect Transistors • NFETs can solve two major nanopore issues • A NFET is simply a device which uses the principals of electrokinetics to tune the velocity of a fluid close to it’s surface • The two phenomenon important to NFETs and molecular sensing are: • Electrophoresis: motion of particles induced by an electric field • Electroosmosis: motion of the bulk fluid due to an electric field
3 Different types of NFETs • Plain Dielectric Surface • Our model advances the science by being the first to consider the effect of Stern Capacitance on channel dynamics • Soft Layer of Charge-Regulated molecules • Our model advances the science by being the first to consider charge regulation in a NFET • Soft Layer of non-regulated molecules • This model is accurate for certain types of soft layer fabrication processes
Plain Dielectric Surface NFET • The electrical double layer consist of: • Stern Layer: Immobile counter-ion layer (typically 1 ionic diameter thickness) • Diffuse Layer: Higher concentration of counter-ions to satisfy electroneutrality (thickness of a debye length) • Previous studies of NFETs have ignored the stern layer, due to the small thickness • This assumption is not valid for all conditions likely in a nanochannel
NFETs cont’d EDL : Electrical Double Layer EOF : Electroosmotic Flow Ez : Electric Field ; Vg : Gate Voltage
Circles Represent Published Experimental Data In both cases, a small capacitance fits experimental data best Verification of our Model
Low Salt Concentration High Salt Concentration Affect on Zeta due to Cs
Low Salt Concentration High Salt Concentration Affect on Velocity due to Cs
The Gated, Charge-Regulated/Charge-Fixed Nano Channel Dielectric Layer Soft Layer Bulk Salt Solution Gate Potential
Analytical Methods • COMSOL Soft Layer Bulk Layer Trans side Wafer Cis side Pore 2nd Generation Model 1st Generation Model
Comparisons between Fixed and Charge Regulated Nano Channels Interesting Results
The Gated, Charge-Regulated Nanopore • Gate Electrode with the soft layer is a unique study • Experimental data for Soft layer model exists • Soft layer adds complexity to fabrication
Fabrication • ALD • RF Sputtering • FIB (focused Ion Beam)
Problems with current technology • Scientists and engineers have already made considerable contributions to developing nanopore based molecular sensors • Two major issues remain: • The Capture rate is too low • The DNA must be threaded through the pore • The Translocation rate is too high • When the DNA reaches the pore, it passes through too quickly (1bp/μs)
Solving Translocation Speed • Two Forces are responsible for the DNA Translocation • Electrophoretic Force • Hydrodynamic Force • Electric forces become strongest inside Pore • NFET can reduce total force on particle, thus tuning translocation speed
Solving Capture Rate • By adding a gate to the outer membrane surface, we theorize that can use the electric field to hydro-dynamically coax the particles toward the pore
Conclusion / Moving Forward • We have already generated our results from the one dimensional nanochannel models • We will simulate the velocity response in a nanopore due to adding NFETs to the channel and upstream (cis) wall of the membrane. • Our hope is too show that the cis electrode can significantly improve the capture rate