Silicon Nanomembrane-based Nanophotonic Devices for Communications and Biosensing Ray T. Chen Microelectronics Research Center, Electrical and Computer Engineering Department, University of Texas at Austin Austin, TX,
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Silicon Nanomembrane-based Nanophotonic Devices for Communications and Biosensing Ray T. Chen Microelectronics Research Center, Electrical and Computer Engineering Department, University of Texas at Austin Austin, TX, 78758, USA * [email protected] Funded by AFOSR MURI for Silicon Nanomembranes NIH, EPA, US Army, MDA and NSF 5/15/2014 Introduction Optical Phased Array Novel System Applications Identification Si NM Device Reliability& Manufactur ability Slow Light Photonic Crystal Waveguides Transferrable Si NM Basic Research with needed Optical and Electronic Properties 2 On-chip Optical Interconnects On-chip Open Sensors for Diverse Pathogen Detection Environmental Human Health Homeland Security National Defense RFID CMOS Compatibility is the Key !!! On-Chip PCW True Time Delay (TTD) Module (a) 1mm CH-4 CH-3 CH-2 CH-1 (b) (d) Photonic crystal taper Slow Light PCW (e) Slow Photonic Light crystal PCW taper 20μm (c) 10μm 1μm 1μm C.-Y. Lin, H. Subbaraman, A. Hosseini, A. X. Wang, L. Zhu, and R. T. Chen, Applied Physics Letters (Submitted) (2012). 11/6/2015 3 Schematic of Testing Setup and Results (a) TUNABLE LASER L RFIN MZM EDFA Photonic crystal waveguide (b) 1x4 MMI (c) PHOTODETECTOR LNA TTD Strip waveguide t = DF Dw Channel-2 (d) 1550nm 65ps Increase λ Vector Network Analyzer 1557nm 126ps Increase λ Channel-3 1561.5nm 217ps Increase λ 1570nm Channel-4 Max ng=23 C.-Y. Lin, H. Subbaraman, A. Hosseini, A. X. Wang, L. Zhu, and R. T. Chen, Applied Physics Letters (Submitted) (2012). 11/6/2015 4 Transfer of Si NM Nanophotonic Devices for Biosensing Application From Photon Manipulation to Photon Detection with Unprecedented Sensitivity for Label-free Biomarkers Detection with High Specificity 6 Photonic Crystal Structures in Nature and in Nanofabrication Opal, the best known periodical structure in nature. 7 Photonic Crystals and Defects Periodic variation of refractive index (Artificial) Periodic atomic structure (Natural) Photonic Bandgap ω Electronic Bandgap Photonic Crystals Semiconductors Introduction of defects k Trapped Carriers Schrődinger Equation { Electronic Bandgap hν } Photonic Bandgap k 1000 Electronic Dispersion Photonic Dispersion Eigenvalue Problem Introduction of defects PC resonant cavities and waveguides Maxwell’s Equations Photonic Crystal for Early Cancer Detection Slow Light Trapped Light Sub-Micron scale Guiding and Confinement of Light 9 Silicon Nanophotonic Biosensor Chip for Lung Cancer Detection Figure of merits of our cancer detection chip in reference to all existing results [1-12] [1] J. Waswa, J. Irudayaraj, C. Deb Roy, “Direct detection of E-Coli O157: H7 in selected food systems by a surface plasmon resonance biosensor”, LWT-Food Science and Technology 40 (2), 187 (2007). [2] M.G. Scullion, et al., “Slotted photonic crystal cavities with integrated microfluidics for biosensing applications”, Biosens. Bioelectron. 27, 101-105 (2011). [3] S. Mandal, D. Erickson, “Nanoscale optofluidic sensor arrays”, Opt. Exp.16(3), 1623 (2008). [4] S. Pal, et al., “Silicon photonic crystal nanocavity-coupled waveguides for error-corrected optical biosensing”, Biosens. Bioelectron. 26, 4024 (2011). [5] C.F. Carlborg, et. al, “A packaged optical slot-waveguide ring resonator sensor array for multiplex label-free assays in labs-on-chips”, Lab on a Chip 10, 281 (2010). [6] K. De Vos, et al., “Silicon-on-insulator microring resonator for sensitive and label-free biosensing”, Opt. Exp. 15 (12), 7610 (2007). [7] C.A. Barrios, “Optical slot-waveguide based biochemical sensors”, Sensors 9, 4751 (2009). [8] S. Zlatanovic, et al., “Photonic crystal microcavity sensor for ultracompact monitoring of reaction kinetics and protein concentration”, Sens. and Actuators B 141, 13-19 (2009). [9] H. Li, X. Fan, “Characterization of sensing capability of optofluidic ring resonator biosensors”, Appl. Phys. Lett. 97, 011105 (2010). [10] B.T. Cunningham, et al, “Label-free assays on the BIND system”, J. Biomol. Screen. 9, 481 (2004). [11] M. Iqbal, et al., “Label-Free Biosensor Arrays based on silicon ring resonators and high-speed optical scanning instrumentation”, IEEE J. Sel. Top. Quant. Electron. 16(3), 654 (2010). [12] Y. Zou, S. Chakravarty, W-C. Lai, R.T. Chen, “High yield silicon photonic crystal microcavity biosensors with 100fM detection limit”, Proc. of the SPIE 8570, 857008 (2013) and S. Chakravarty, Y. Zou, W-C. Lai, R.T. Chen, “Slow light engineering for high Q high sensitivity photonic crystal microcavity biosenors in silicon”, Biosensors and Bioelectronics 38(1), 170 (2012). Center Overview 10 • 50fM concentration of avidin binding to biotin detected • High sensitivity demonstrated at 0.1mg/ml • High “working device” yield of photonic crystal microcavity biosensors using sub-wavelength grating couplers • Repeatable resonance wavelength shifts • CMOS platform--- low cost during high volume manufacturing • 64 Multiplexed Devices for Microarrays demonstrated. It can go as high as 1024 different biomarker detection if needed 11 Intensity (a.u.) Principle of Operation Intensity (a.u.) Wavelength (nm) Wavelength (nm) 12 Intensity (a.u.) Principle of Operation Intensity (a.u.) Wavelength (nm) Wavelength (nm) 13 Intensity (a.u.) Principle of Operation Intensity (a.u.) Wavelength (nm) Wavelength (nm) 14 Chip-Integrated Microarray for High Throughput Highly Sensitive Highly Specific Cancer Detection Prototype system demonstrated at Baylor College of Medicine in May 2013 Translation to portable platforms possible 15 Formation of Microfluidic Channels 16 Three stages of Biomarker Detections A. B. C. Pure antibody-Antigen reaction (for proteinprotein reaction) Biomarker in cell lysate (for in-vitro research purpose) Biomarker in real patient serum (for clinical diagnosis) 17 Breast Cancer Biomarker Detection in Serum Baseline Probe-EGFR Antibody Target-EGFR Antigen EGFR: Epidermal Growth Factor Receptor is the cellsurface receptor Sensitivity and Specificity for Lung Cancer Detection Specificity is achieved with Label-free Sandwich Assays • Resonance Wavelength Shift with Induced Lysate in PBS. • No Resonance Wavelength Shift with Un-Induced Lysate in PBS. • Secondary Supershift with secondary antibody in PBS: Sandwich • Specificity demonstrated further with isotype matched control mouse IgG1 • Secondary Supershift with secondary antibody in PBS: Sandwich Chakravarty et al., Biosensors and Bioelectronics 43, 50 (2013) Multiplexed Sensitivity and Specificity Induced Lysates Immobilized Antibodies 4 PC Microcavities in Silicon 1 1. BSA 2 IgG 2. Mouse 3 3. Anti-ZEB1 4. Anti-MYC 4 9E10 MYC 9E10 Induced Lysates to attach to ZEB-1 and MYC 9E10 1 2 3 4 ZEB Chakravarty et al., Biosensors and Bioelectronics 43, 50 (2013) Multiplexed Sensitivity and Specificity l1 No Shift l2 No Shift l3 Shift l4 Shift Mouse IgG1 Washing in PBS Induced Lysates Immobilized Antibodies 4 PC Microcavities in Silicon 1. BSA 2. Mouse IgG 3. Anti-ZEB1 4. Anti-MYC 9E10 MYC 9E10 Induced Lysates to attach to ZEB-1 and MYC 9E10 1 2 3 4 ZEB Chakravarty et al., Biosensors and Bioelectronics 43, 50 (2013) Multiplexed Sensitivity and Specificity l1 No Shift l2 No Shift l3 No Shift l4 No Shift Anti-MYC 9E10 Washing in PBS Mouse IgG1 1. BSA 2. Mouse IgG 3. Anti-ZEB1 4. Anti-MYC 9E10 MYC 9E10 Induced Lysates to attach to ZEB-1 and MYC 9E10 1 2 3 4 ZEB Chakravarty et al., Biosensors and Bioelectronics 43, 50 (2013) Multiplexed Sensitivity and Specificity Sandwich for Specificity Washing in PBS l3 Super Shift Anti-MYC 9E10 1. BSA 2. Mouse IgG 3. Anti-ZEB1 4. Anti-MYC 9E10 MYC 9E10 Induced Lysates to attach to ZEB-1 and MYC 9E10 1 2 3 4 ZEB Chakravarty et al., Biosensors and Bioelectronics 43, 50 (2013) Sensitivity Amplification by Sandwich Assay • Initial Cell Concentration: 10,000 cells per micro-liter made up of 20K-30K proteins • Samples diluted in PBS: 60 micro-liters in each addition • 10 cells per micro-liter detected without sandwich • 2 cells per micro-liter detected with sandwich assisted amplification 1 1 2 ZEB1 detected from among 20K-30K proteins 2 10 100 1000 5000 0d Cells per micro-liter T2 Chakravarty et al., Biosensors and Bioelectronics 43, 50 (2013) Binding Measurements Probe Protein Binding Target Protein Binding Lai et al. Optics Lett. 37, 1208 (2012) 25 Low Cost of Ownership Chip-Integrated Microarray for High Throughput Highly Sensitive Highly Specific Cancer Detection Omega Optics Inc., Austin, TX Slowing Light for Sensitive Diagnostics Competitive Advantage: Price of consumables < 50% Biacore 4000 (GE) Bench-Top System Price <50% Biacore 4000 (GE) Biacore acquired for $436M in 2006 Patent Position: 7 issued , 4 pending; more in pipeline, 6 from UT. Team: Omega Optics, University of Texas, Austin; MD Anderson Cancer Center (Breast Cancer); Medical Univ. of S. Carolina (Lung Cancer). Contact: Dr. Ray Chen, CTO, [email protected], 512-825-4480 26 64 Highly Multiplexed Early Cancer Detection Chip 27 Fabrication and testing of 1x16 splitter Xu et al. IEEE Photonics Technology Letters, Vol. 25, No.16, pp.1601-1604 (2013) Test Result of 64 Highly Multiplexed Early Cancer Detection Chip 29 L3 series devices L55 devices L13 device- high magnification Integrated Sample Preparation and Sensors on a Chip with User-Friendly Machine-Human Interface Fast Plasma Separation on Chip Light Out Sensor Arrays on Chip Sample Preparation on Chip Light In Silicon Nanophotonic Devices for Early Cancer Detection Selective CTC Capturing An Open Platform for High Value Biomarker Detection APPLICATION Lung Cancer Breast Cancer BIOMARKER IL-10 Antibody Annexin 11 Protein TARGET TYPE Protein Protein Mesothelioma Melanoma Osteopontin Antibody GM3 Antibody Protein Lipid DNA/RNA/mR NA Protein AIDS HIV Gene Bacteria/Virus Infection Anti-HCV Antibody Anti-Amphotericin B Therapeutic Drug Ab Signal Transduction Pathway P53 Antibody Cancer Stem Cell Protein Protein Open Sensor Systems on Silicon PCW Chip What has been demonstrated On Semiconductor Nanomembranes Early Cancer Detection (NIH)* Air-pollution (Methane gas) Sensor(EPA)* Water-pollution (Xylene) Sensor (NSF)* Sensor for National Security (Chemical Warfare Simulant TEP Triethylphosphate, funded by US Army)* EM-Wave Sensor (Missile Defense Agency)* *: Peer-reviewed Journal publications available or to be available Issued US Patents • “Photonic Crystal Microarray Device for Label-free Multiple Analyte Sensing, Biosensing and Diagnostic Assay Chips,” Patent 8293177 (Issued: 10/23/2012) US Patent and Trademark Office (2009). (Omega Optics Inc.) • “Photonic Crystal Slot Waveguide Miniature On-Chip Absorption Spectrometer,” Patent 8282882 (Issued: 10/09/2012) US Patent and Trademark Office (2010). (Omega Optics Inc.) • “Method for Label-Free Multiple Analyte Sensing, Biosensing and Diagnostic Assay,” Patent Application # 13607791, US Patent and Trademark Office (2012). (Omega Optics Inc.) • “Method for the Chip-Integrated Spectroscopic Identification of Solids, Liquids, and Gases,” Patent Application # 13607792, US Patent and Trademark Office (2012). (Omega Optics Inc.) • “Packaged chip for multiplexing photonic crystal waveguide and photonic crystal slot waveguide devices for chip-integrated label-free detection and absorption spectroscopy with high throughput, sensitivity, and specificity,” Patent Application # 13607801, US Patent and Trademark Office (2012). (Omega Optics Inc.) • “Photonic Crystal MicroArray Layouts for Enhanced Sensitivity and Specificity of Label-Free Multiple Analyte Sensing, Biosensing and Diagnostic Assay,” Patent Application # 13607793, US Patent and Trademark Office (2012). • “Fabrication Tolerant Design for the Chip-Integrated Spectroscopic Identification of Solids, Liquids, and Gases,” Patent Application # 13607794, US Patent and Trademark Office (2012). Contact: Dr. Ray Chen, CTO, [email protected], 512-825-4480 36 Low Cost of Ownership Chip-Integrated Microarray for High Throughput Highly Sensitive Highly Specific Cancer Detection Omega Optics Inc., Austin, TX Slowing Light for Sensitive Diagnostics Issued Patents: University of Texas Austin • “Multimode Interface Coupler for Use with Slot Photonic Crystal Waveguides,” Provisional Application 61/092,672 (2008). • “Broadband, group index independent, and ultra-low loss coupling into slow light slotted photonic crystal waveguides”, PCT Conversion, WO 2013/048596 A2 (2012) • “Subwavelength grating coupler”, Provisional Application 61/770,694 (2013). Contact: Dr. Ray Chen, CTO, [email protected], 512-825-4480 37 Potential Collaborations 38 Thank You from Austin 11/6/2015 39