SNP Biochip with Electrical Detection and Gold Nanoparticles

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SNP Biochip with Electrical Detection and Gold
Nanoparticles

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• Prof. Ping-hei Chen
• Department of Mechanical Engineering
• National Taiwan University

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Array-Based Electrical Detection of DNA with
Nanoparticle Probes
Single Nucleotide Polymorphism (SNP)
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NanoDevice

NanoDevice NanoMaterial

Nanoparticles
SNP Chip
Self Assembly
measurement
Material Properties
Integration
Device
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SNP Chip
100nm
PROCESS BY E-beam writer
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Principle for electrical detection of DNA
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SNP Chip
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Self-Assembly of AuNP Monolayer
THMS
Silanization
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Self-Assembly of AuNP Multilayer
alkanethiol-cDNA
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Single layer
Multi-layer
Measurements are taken in atmosphere and at room
temperature, but no solution between the
electrodes
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DNA with AuNP
No AuNP
Monolayer
Mutlilayer
In atmosphere, but no solution in the gap
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FE-SEM images of the AuNPs before and after
denatured
Fig (A) Complementary tDNA hybridization before
denatured (B)
Complementary tDNA hybridization after
denatured
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FE-SEM images of the AuNPs before and after
denatured
Fig (Left) IV curve for complementary tDNA
hybridization before denatured
(Right) IV curve for complementary
tDNA hybridization after denatured

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FE-SEM images of the AuNPs multilayer by using
different concentration of tDNA hybridization
A
B
C
D

• Fig (a) 0.1 µM, (b) 1 nM, (c) 10 pM, and (d) 1fM
  with the complementary cDNA and pDNA strands were
  assembled on the SiO2 substrates following the
  same procudure used for DNA detection.

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The electronic measurement results of nano-gap
measured by using different tDNA concentration

• Fig I-V curves of the nano-gap electrode
  measured by using different tDNA concentration
  which detected in the (A) 0.1 µM, (B) 1 nM, (C)
  10 pM, and (D) 1fM range. Here, tDNA were
  cohybridized to cDNA and pDNA in 0.3 M PBS for 2
  hours in all experiments

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Results with 1 fM tDNA Concentration
350nm
Key How to improve the area coverage with
monolayer AuNP structure?
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FE-SEM images of the AuNPs multilayer for
single-bp Mismatch
Fig. (a) FE-SEM image for multilayer of AuNPs for
single-bp mismatch tDNA hybridization before
denaturing. (b) FE-SEM image of AuNPs for
Single-bp mismatch tDNA hybridization after
denaturing. Here, the concentration of tDNA for
hybridization is 1nM. The chip was immersed into
a salt solution of 0.01 M NaCl and PBS buffer for
2 hours.
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FE-SEM images of the AuNPs multilayer for
single-bp Mismatch
(left) Current-voltage curve for multilayer of
AuNPs with single-bp mismatch tDNA
hybridization with a scanning rate of 10 mV/s.
(right) Current-voltage curve for AuNPs layer
after the chip with the single-bp mismatch tDNA
after denaturing.
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CMOS processed SNP
temperature sensor

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  ?testkey

post-process testkey
biosensor microstructures
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CMOS processed SNP
biosensor microstructures
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CMOS processed SNP
biosensor microstructures
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CMOS processed SNP
biosensor microstructures
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CMOS processed SNP
biosensor microstructures
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CMOS processed SNP
biosensor microstructures
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biosensor microstructures
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Conclusions

1. Electrical measurement for DNA detection is made
   possible through gold nanoparticles and nanogap
   electrodes.
2. A CMOS biochip using this electrical measurement
   for DNA detection is fabricated by TSMC. It
   proves that this biochip can be massively
   produced through a batch process. In future, this
   biochip can be used for a massive screening.
3. If the detection concentration of tDNA can be
   lowered to 1 fM, no PCR for tested sample is
   required for this biochip.
4. A single-bp mismatch between oligonucleotides can
   be detected by using the current technique.

biosensor microstructures