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Structural optimization for heat detection of DNA thermosequencing platform using finite element analysis
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1.F. Sanger, S. Nicklen, and A. R. Coulson, Proc. Natl. Acad. Sci. U.S.A. 74, 5463 (1977).
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Image of FIG. 1.

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FIG. 1.

Schematic of thermosequencing platform.

Image of FIG. 2.

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FIG. 2.

The time-dependent concentrations of dNTP and PPi at the well bottom are shown for the 2D simulation. The dNTP concentration asymptotically increases to equilibrate with the 3 mM dNTP concentration in the channel. The maximum PPi concentration at the well bottom is 0.1407 mM (time scale is in seconds).

Image of FIG. 3.

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FIG. 3.

Control channel schematics for the double (top left) and single (bottom left) control line systems. In both cases, pressurization of the control channels induces expansion for mass and thermal insulation of the well. The double-control line system for a -wide channel is shown at right.

Image of FIG. 4.

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FIG. 4.

Time-dependent PPi concentrations are plotted for the open-channel, two-control-line and one-control-line models of thermosequencing. The one-control-line PPi concentration begins to increase more quickly than the others because it is assumed that, when the control line begins pressurizing, the expansion will convectively drive dNTP into the well for faster reaction.

Image of FIG. 5.

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FIG. 5.

The time-dependent temperature change at the well bottom is shown for the 2D simulation. The temperature change is at 0.5 s.

Image of FIG. 6.

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FIG. 6.

Comparison of the temperature change for the open-channel, two-control-line and one-control-line systems from 0 to 0.5 s. It is apparent that the insulated systems have higher temperature change due to the decrease in the thermal conductivity and the decreased heat absorption by the fluid surrounding the reaction.

Image of FIG. 7.

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FIG. 7.

The temperature change in the one-control channel system with Invitrogen Dynabead™ at 0.5 s. The density, heat capacity, and thermal conductivity characteristics are calculated and simulated. The difference in temperature change between this model and the standard one-control channel system is around .

Image of FIG. 8.

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FIG. 8.

A comparison of the temperature change in sequencing platforms of two different sizes. The size system (top) is the aforementioned two-control channel system. The size system (bottom) is the same two-control channel system increased in volume by 1000. The limits on the diffusive flow of dNTP are seen as the size system is actively heating up the system at 2 s while the size system reaches thermal and reaction steady state.


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Table I.

Reaction series constants.


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For the past three decades, Sanger’s method has been the primary DNAsequencingtechnology; however, inherent limitations in cost and complexity have limited its usage in personalized medicine and ecological studies. A new technology called “thermosequencing” can potentially reduce both the cost and complexity of DNAsequencing by using a microfluidic platform [Esfandyarpour, Pease, and Davis, J. Vac. Sci. Technol. B26, 661 (2008)]. To optimize the efficiency of the technology,finite element analysis was used to model the thermosequencing system by simulating the DNA incorporation reaction series and the resulting product concentration and heat production. Different models of the thermosequencing platform were created to simulate the effects of the materials surrounding the system, to optimize the geometry of the system, and to concentrate reaction heat into specific regions for detection in the real system. The resulting concentrations of reaction products were used to calibrate the reaction speed and to design the heat sensors in the thermosequencing technology. We recommend a modified gated structure for the microfluidic detection platform by using control valves and show how this new platform could dramatically improve the detection efficiency.


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Scitation: Structural optimization for heat detection of DNA thermosequencing platform using finite element analysis