Detection of several cancer biomarkers by. semiconductor Si nanowires

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1 VIETNAM NATIONAL UNIVERSITY HO CHI MINH CITY LABORATORY FOR NANOTECHNOLOGY Detection of several cancer biomarkers by semiconductor Si nanowires Laboratory for Nanotechnology Viet nam National University at HoChiMinh Linh Trung, Thu Duc, Ho Chi Minh City Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 1

2 Content Introduction about Laboratory for Nanotechnology (LNT) Introduction ti about nanowire nanosensor Fabrication of complete nanowire nanosensors at LNT Detection of several biomarkers for diagnosing of breast, prostate & liver cancers at LNT Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 2

3 Vietnam National University - Ho Chi Minh City (VNU-HCM) Laboratory for Nanotechnology (LNT) Laboratory for Nanotechnology (LNT) -Research Institution tut of International Standard Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 3

4 I. Introduction about LNT The Laboratory for Nanotechnology (LNT) was officially established in September LNT has the following missions: Developing the scientific research in Micro-Nanotechnology and transferring research results from universities to industry, Supporting industrial sectors for doing research on materials and microelectronics, Teaching the Micro-Nanotechnology for graduate and postgraduate programs, Collaborating with joint-ventures and foreign companies for doing research, training and technology transfer in microelectronics and other sectors. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 4

5 Technological Facilities of LNT The LNT owns the Clean Room of with class for micro/nano device fabrication, characterization ti and applications Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 5

6 Technological Facilities of LNT Manufacturing of Micro and Nano Devices: Photolithography, Wet etching and dry etching (RIE), Thermal treatment (Oxidation / Annealing furnace), Packaging (Dicing equipment, Bonding equipment), Characterization (Surface Profiler, Optical thickness measurement equipment). Structure Characterization and Nano Manipulation: Scanning Electron Microscopy - SEM with EDS, Micro Raman spectroscopy, Atomic Force Microscopy - AFM, Scanning Tunneling Microscopy -STM. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 6

7 Core Research groups at LNT Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 7

8 Internal and external collaborations For conducting micro and nanotechnology for health I. Internal collaboration: 02 biggest National Cancer hospitals, Electronics Department of University of Natural Science (UNS) of VNU; Biology Department of UNS, Hanoi University it of Technology, National Institute for Epidemics diseases etc II. External collaboration: Having direct and closed collaborations with ca. 10 international research groups III. Research projects: Currently running 05 research projects, including 02 key national research projects and 02 VNU key projects, All projects relating to early diagnosing of diseases Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 8

9 II. Introduction about nanowire nanosensor Definition: Nanowires are wires having at least one dimension from 1 to 100 nm; Your hair has diameter of nm; So, bundling at least ca nanowires = the size of your hair. ( very small, ultra high surface to volume ratios...) bundle nanowires single, selected wire Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 9

10 Nanowires with many new properties p and applications Ultrahigh surface to volume ratios, New phenomena and properties: quantum confinement, strong influence of surface processes to resistance... New devices with completely new capabilities and functions in: optics, electronics, magnetics, laser,... and especially in sensor technology Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 10

11 Nanowire nanosensor: working principle ASinanowire-based FET device configured as a sensor with antibody receptors (green), where binding of a protein with net positive charge (red) yields a decrease in the conductance. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 11

12 Multiplexed detection Array of nanowires, coated with different bioreceptors for electrical and multiplexed detections Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 12

13 Configuration of nanowire nanosensor SEM image of a Si nanowire FET sensor and Packaging with microfluidics and electronics; Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 13

14 Advantages of nanowire nanosensors + Biological recognition gives high selectivity, + Molecular size of the wire give high sensitivity ( down to even single molecular level) + Label free, electrical read out (rapid, real-time -on-line), + Simultaneous and multiplexed detections Bring New applications and possibilities in: Drug discovery, Food quality control (gene mutation...), Biological & chemical warfare, Environment quality control (gases, water...), Especially, an detection of cancer biomarkers for early diagnosis Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 14

15 Biological detections by using nanowire nanosensors Single virus detection in real-time Patolsky et al., Proc. Natl. Acad. Sci., 101, (2004). Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 15

16 Protein detection Real time detection ti of protein binding. SiNW surface was modified d by biotin to detect streptavidin, detection limit of about 10 pm. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 16

17 DNA and DNA sequence variation detection + The ΔF508 mutation is responsible s e for 75% of the cases of the disease of Cystic fibrosis, one of the most common fatal genetic diseases. + SiNW was modified by peptide nucleic acid (PNA) that can distinguish wild- type from the ΔF508 mutation site in the cystic fibrosis transmembrane receptor (CFTR) gene. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 17

18 Small molecule-protein interaction detection The protein (tyrosine kinase Abl) is covalently linked to the surface of a SiNW, and then the conductance of the nanowire device is monitored to detect ATP binding and the competitive inhibition of ATP binding by Gleevec. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 18

19 Multiplexed electrical detection of prostate cancer markers + Detection of prostate specific antigen (PSA) down to 0.9 pg/ml in undiluted serum; times more sensitive than conventional methods; + Can be used for detecting other cancers and diseases (More details: Zheng et al., Nature biotechnology, September, 2005.) Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 19

20 Other examples of cancer biomarker detections Nanowire-Based Nanoelectronic Devices in the Life Sciences, F. Patolsky et al., MRS bull. 32, (2007). Electrical detection of VEGFs for cancer diagnoses using antivascular endotherial growth factor aptamer-modified Si nanowire FETs, Hyun-Seung Lee et al., Biosensors and Bioelectronics 24 (2009) Nanowire sensors for multiplexed detection of biomolecules, Bo He et al., Current Opinion in Chemical Biology 2008, 12: Label-free biomarker detection from whole blood, Eric Stern et al., Nature Nanotechnology, Volume 5, Issue 2, pp (2010). Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 20

21 III. Fabrication of complete nanowire nanosensors at LNT Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 21

22 Existing Problems of Nanowire technology + Problems: nanowire FET sensors fabricated by complicated & time consuming processes -> very high sensor cost (up to k$), low reproducibility... Bundle nanowires Select good one Make contacts (E-beam lithography) These limitations have rendered further studies and applications of nanowire devices. Therefore, although h huge interest, t investment, t and study, but the devices are not commercially available yet. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 22

23 Our newly developed technology for Inexpensive, wafer-scale nanowires + We have developed a new method that uses conventional IC techniques to pattern wafer-scale nanowires of many materials including metals, alloys, oxides, semiconductors etc ) + Generally, the newly developed technique uses the conventional IC technology, thin film depositions (both physical and chemical routes), and a normal etching to make the nanowires on the bearing wafers of silicon, glass, quartz, or even plastics. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 23

24 Wafer scale nanowire fabrication by Deposition and Etching Under Angle method (DEA) Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 24

25 Our fabricated nanowires Single nanowire Single nanowire with individual electrical contacts Hien Duy Tong et al., Nanoletter, vol. 9, No.3, pp , March, P. Offermans and Hien Duy Tong et al., Apply Physic Letter, Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 25

26 Ready for measurement silicon nanowires Single nanowire with micro-contact paths to outer-world (control electronics), thus ready for measuring the biomarkers for cancer detection Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 26

27 Our fabricated nanowires Array of Si nanowires for multiplexed detections Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 27

28 Our ready for measurement nanowire chips Version 1 Version 2 Version 3 Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 28

29 Measurement setup LNT has complete setups, including: + Chemical line for surface modification ( to bind the bioreceptors on the surface of nanowires), and + Electrical line for electrical detection of cancer biomarkers Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 29

30 On going work of cancer detection + After a couple of research and development years, We have mastered the fabrication technology to produce: Inexpensive & ready measurement Si nanowire chips + We now move to second phase of the project: Utilization of the developed Si nanowire chips for Ultrasensitive and multiplexed detection of several Biomarkers for diagnosing of cancers. + The interest cancers are: prostate, breast, & liver cancers Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 30

31 Biomarkers for cancer detection Liver cancer: simultaneous detections at fm of markers Alpha-fetoprotein (AFP), AFP-L3, Des-gamma-carboxyprothrombin (DCP) & Protein (GP73) This will really enhance an accuracy for diagnosing Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 31

32 Biomarkers for cancer detection in our research Prostate cancer: + Detection of prostate specific antigen (PSA) + In particular, the expression of TMPRSS2:ERG fusion gene originating i i from circulating i tumor cells (CTC) and its potential for monitoring prostate cancer with nanowire technology will be investigated. The direct detection of CTC's with nanowire technology will also be explored. Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 32

33 THANKS FOR YOUR ATTENTION Laboratory for Nanotechnology Vietnam National University of Ho Chi Minh city 33