Qintao Zhang

EECS Department, University of California, Berkeley

Technical Report No. UCB/EECS-2007-170

December 20, 2007

http://www2.eecs.berkeley.edu/Pubs/TechRpts/2007/EECS-2007-170.pdf

This thesis describes an ultra-low-cost, disposable, portable and fast DNA hybridization detection system integrating Organic Thin Film Transistor (OTFT) based DNA sensors with microfluidic systems. OTFTs have attracted significant attention in recent decades for use in low-cost Radio Frequency Identification (RFID) tags and driver circuits for flexible displays, but their biological applications is still very rare. The capability of OTFTs on DNA detection was studied in this thesis. Because of their electrical-readability, OTFT based gene analysis toolkits greatly solve problems faced by current DNA detection systems, including expensive instruments and slow processing due to their fluorescence-based detection nature.

To implement this concept, DNA molecules were immobilized directly on the exposed channels of bottom-gated organic transistors. By carefully characterizing transistors, the doping mechanism caused by immobilized DNA was studied. Importantly, unhybridized and hybridized DNA molecules show substantial difference in the resultant threshold voltage shift due to their different net doping and immobilization efficiencies. Thus, this method clearly enables direct electrical detection of hybridization through measuring OTFT saturation current. To dramatically speed up the analysis process, the pulse-enhanced DNA hybridization method was used to achieve hybridization in less than a millisecond. The net result of the research on OTFT DNA sensor is an overall analysis time of less than 40 minutes, compared with more than 24hrs using conventional techniques.

As a further step, a microfluidic system on OTFTs was built to automatically deliver DNA to detection sites. By carefully studying controllability of etching rate of the Polyvinyl Alcohol (PVA) film, a water-soluble polymer, a SU-8-based microfluidic system was patterned photolithographically on OTFTs as the first time. The process was proven not to change the morphology of pentacene film, and because the etchant is DI water, the process-induced performance shift is acceptable for following successful DNA detection. Even importantly, the integration of microfluidic system with OTFT DNA sensor dramatically drops data variance, thus enabling on-chip hybridization detection. Combing OTFT-based DNA sensors with microfluidic systems, the overall results of the research will enable the deployment of gene chip techniques for disposable field-deployable diagnosis toolkits, facilitating personalized medicine research and early-stage disease diagnosis.

Advisors: Vivek Subramanian

---

BibTeX citation:

@phdthesis{Zhang:EECS-2007-170,
    Author= {Zhang, Qintao},
    Title= {OTFT-based DNA Detection System},
    School= {EECS Department, University of California, Berkeley},
    Year= {2007},
    Month= {Dec},
    Url= {http://www2.eecs.berkeley.edu/Pubs/TechRpts/2007/EECS-2007-170.html},
    Number= {UCB/EECS-2007-170},
    Abstract= {This thesis describes an ultra-low-cost, disposable, portable and fast DNA hybridization detection system integrating Organic Thin Film Transistor (OTFT) based DNA sensors with microfluidic systems. OTFTs have attracted significant attention in recent decades for use in low-cost Radio Frequency Identification (RFID) tags and driver circuits for flexible displays, but their biological applications is still very rare. The capability of OTFTs on DNA detection was studied in this thesis. Because of their electrical-readability, OTFT based gene analysis toolkits greatly solve problems faced by current DNA detection systems, including expensive instruments and slow processing due to their fluorescence-based detection nature.

To implement this concept, DNA molecules were immobilized directly on the exposed channels of bottom-gated organic transistors. By carefully characterizing transistors, the doping mechanism caused by immobilized DNA was studied. Importantly, unhybridized and hybridized DNA molecules show substantial difference in the resultant threshold voltage shift due to their different net doping and immobilization efficiencies. Thus, this method clearly enables direct electrical detection of hybridization through measuring OTFT saturation current. To dramatically speed up the analysis process, the pulse-enhanced DNA hybridization method was used to achieve hybridization in less than a millisecond. The net result of the research on OTFT DNA sensor is an overall analysis time of less than 40 minutes, compared with more than 24hrs using conventional techniques.

As a further step, a microfluidic system on OTFTs was built to automatically deliver DNA to detection sites. By carefully studying controllability of etching rate of the Polyvinyl Alcohol (PVA) film, a water-soluble polymer, a SU-8-based microfluidic system was patterned photolithographically on OTFTs as the first time. The process was proven not to change the morphology of pentacene film, and because the etchant is DI water, the process-induced performance shift is acceptable for following successful DNA detection. Even importantly, the integration of microfluidic system with OTFT DNA sensor dramatically drops data variance, thus enabling on-chip hybridization detection. Combing OTFT-based DNA sensors with microfluidic systems, the overall results of the research will enable the deployment of gene chip techniques for disposable field-deployable diagnosis toolkits, facilitating personalized medicine research and early-stage disease diagnosis.},
}

EndNote citation:

%0 Thesis
%A Zhang, Qintao 
%T OTFT-based DNA Detection System
%I EECS Department, University of California, Berkeley
%D 2007
%8 December 20
%@ UCB/EECS-2007-170
%U http://www2.eecs.berkeley.edu/Pubs/TechRpts/2007/EECS-2007-170.html
%F Zhang:EECS-2007-170