SNP Biochip with Electrical Detection and Gold Nanoparticles

1. SNP Biochip with Electrical Detection and Gold Nanoparticles 陳炳煇教授 Prof. Ping-hei Chen Department of Mechanical Engineering National Taiwan University

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

3. NanoDevice NanoDevice NanoMaterial Nanoparticles SNP Chip Self Assembly measurement Material Properties Integration Device

4. 100nm GAP SNP Chip 100nm PROCESS BY E-beam writer

5. Principle for electrical detection of DNA e- 100nm

6. SNP Chip

7. Self-Assembly of AuNP Monolayer THMS Silanization

8. Self-Assembly of AuNP Multilayer alkanethiol-cDNA

9. Single layer Multi-layer Measurements are taken in atmosphere and at room temperature, but no solution between the electrodes

10. DNA with AuNP No AuNP Monolayer Mutlilayer In atmosphere, but no solution in the gap

11. A B FE-SEM images of the AuNPs before and after denatured Fig: (A) Complementary tDNA hybridization before denatured (B) Complementary tDNA hybridization after denatured

12. 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

13. 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.

14. 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

15. Results with 1 fM tDNA Concentration 350nm Key: How to improve the area coverage with monolayer AuNP structure?

16. a b 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.

17. 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.

18. CMOS processed SNP temperature sensor • 奈米粒子暨電極式微陣列生物晶片主要可分為三個部分：生物感測部分、微結構部分、溫度感測與控制機制及後製程testkey post-process testkey biosensor & microstructures

19. CMOS processed SNP biosensor & microstructures

20. CMOS processed SNP biosensor & microstructures

21. CMOS processed SNP biosensor & microstructures

22. CMOS processed SNP biosensor & microstructures

23. CMOS processed SNP biosensor & microstructures

24. biosensor & microstructures

25. Conclusions: • Electrical measurement for DNA detection is made possible through gold nanoparticles and nanogap electrodes. • 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. • If the detection concentration of tDNA can be lowered to 1 fM, no PCR for tested sample is required for this biochip. • A single-bp mismatch between oligonucleotides can be detected by using the current technique. biosensor & microstructures