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Project Title
Electronic Detection of Genomic Length DNA in Nanochannels
 

Research Program
Biomolecular Devices and Analysis

 
Project #
BDA15
 
Participating Faculty: R. Austin, H. Craighead, S. Tavazoie
NBTC Students/Postdocs: Chih-kuan Tung, John Mannion
Other Students/Postdocs: 
 

Objectives
We have two main objectives: the isolation of genomic material from single cells, and the analysis of the genomic DNA from single cells directly using nanochannels. This project is about the nanochannel work.

Nanochannels: The elongation of genomic length DNA in confining nanochannels is not only a fascinating exercise in polymer dynamics, but also is of great interest in biotechnology because the elongation of the confined molecule is directly proportional to the actual length of the molecule in basepairs. Precision length measurements of genomic length DNA molecules are useful because most of the mutations are not point mutations, but a rearrangement, insertion or deletion of a variety of lengths of segments of the genome within the genome itself. Conducting such measurements without an expensive optical microscope will be of great value for genomic analysis, and electrical measurements should provide the highest resolution. We are developing measurement methods using field-effect transistors (FETs) and electrochemical measurements, and we demonstrate methods to integrate the electronic devices with the nano-fluidics

Methods
Nanochannels: Since DNA molecules are negatively charged in an aqueous solution, FETs can be used to detect the electric fields from the molecules. Our studies show that different characteristic I-V curves are seen when DNA molecules are present in the solution, for FET devices made of carbon nanotubes and poly-silicon film. We also demonstrate that some easy electrical measurements can be used to detect DNA or the bases of DNA by their electrochemical properties.

To integrate the electrical detection with the fluidics, we have developed two different methods to achieve that goal. A channel made with silicon oxide lift-off and anodic bonding can be used to integrate electronics with microchannels, and a self-sealed parylene capped nanochannel can be easily integrated with the electronics. The ability to integrate electronics with nanochannels can eventually lead to an all-integrated single-piece genomic diagnostic system.

Summary
We proposed demonstrated the fabrication of a single, narrow (as small as 11 nm), long (over 1.5 cm) and continuous fluidic channel and the transporting and stretching of DNAs in these channels.  We have also demonstrated nanofabrication of channels which are integrated with electrodes using a room-temperature sealing process which should be scalable to integration with CMOS FET technology for detection and amplification of electronic signals.

Accomplishments

  • Construction of nanochannels using parylene capping for low-temperature processing connection to FETs and carbon nanotubes.
  • Single sub-20 nm wide centimeter long nanofluidic channels

Fig.1: Epi-fluorescence image of fluorescent dye in a nanochannel (bright vertical line at the center) with gold nanoelectrodes electrodes intersecting the nanochanenl (not visible at this scale).  The nanochannel was sealed by parylene processing.

 

Fig.2: Top-down SEM images of (a) a 17 nm wide, 1.5 cm long single nanochannel pattern on an imprint mold (3ó error ) 1.6 nm);

(b) the corresponding 17 nm wide, 1.5 cm long nanochannel directly imprinted in a NXR-3020 UV-curable functional material layer (3ó error ) 3 nm); (c) the 18 nm wide, 1.5 cm long nanochannel subsequently etched in SiO2 by RIE (3ó error ) 6 nm)..

This material is based upon work supported in part by the STC Program of the National Science Foundation under Agreement No. ECS-9876771. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

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