Nanostructured Plasmonic Interferometers for Ultrasensitive Label-Free Biosensing. Fil Bartoli Lehigh University 4/9/2014

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1 Nanostructured Plasmonic Interferometers for Ultrasensitive Label-Free Biosensing Fil Bartoli Lehigh University 4/9/2014

2 P.C. Rossin College of Engineering and Applied Science Department of Electrical and Computer Engineering

3 Smith Family Laboratory for Optical Technologies Lab Members: Qiaoqiang Gan (now at U Buffalo) Yongkang Gan Beibei Zeng Zheming Xin Collaborators: Prof. Xuanhong Cheng (MSE) Bu Wang

4 Outline 1 Introduction Surface plasmon resonance (SPR) biosensors Nanoplasmonic biosensors 2 Plasmonic Mach-Zehnder interferometer for highly-sensitive biosensing Sensor design and fabrication Label-free, real-time biomolecular sensing 3 Plasmonic interferometers for array-based high-throughput sensing Scaling up plasmonic sensors for multiplexed sensing in imaging mode Imaging-based high-throughput sensing experiment 4 Optimization of plasmonic interferometers Design of circular plasmonic interferometer High-performance single-channel sensing High-performance imaging-based multiplexed sensing 5 Summary

5 Biosensors Biosensor applications: fundamental biological research, drug discovery, biomedical diagnostics, environmental monitoring, food testing, homeland security. Global: 8.5 billion (2012) billion (2018) US: 2.6 billion (2012) largest market 1. Fluorescent labeling 2. Label-free detection Time consuming Interfere with target molecules Fast Real-time No labeling A. G. Brolo, Plasmonics for future biosensor, Nature Photonics, 6, 709 (2012) Biosensors - A Global Market Overview, 2012

6 SPR biosensors working principle Underlying physics: the resonant excitation of surface plasmon polaritons (SPPs) ω k = ω c k = ω c n sinθ SPPs - Electromagnetic waves coupled to coherent charge oscillations at a metal-dielectric interface n sinθ = k = ω 0 k = ω c k n ε n + ε

7 SPR biosensors - advantage SPR is used to monitor biomolecular binding events in real time. It can provide binding kinetics, affinity, specificity and concentration, without any need for labels.

8 SPR biosensors-limitations 1. Current prism-coupling design requires bulky, complex, expensive instrumentation (limits the application to research only). Next generation biosensors: low-cost, portable, fast, sensitive. R&D investments have focused on miniaturization. A. G. Brolo, Plasmonics for future biosensor, Nature Photonics, 6, 709 (2012)

9 SPR biosensors-limitations 2. Difficult to increase SPR Imaging throughput Avoid crosstalk between sensing spots (large sensing spot size μm diam.) No use of high NA optics for magnification to increase signal/noise ratio Low throughput, not suitable for single-cell analysis

10 Nanoplasmonic biosensors Nanoplasmonic sensors employ nanoparticles, nanoaperture arrays to couple light directly into SPPs in a simple collinear transmission setup. 1. Promising for low-cost portable biosensors 2. Small footprint, high NA optics, high throughput J-C Yang et. al., Metallic Nanohole Arrays on Fluoropolymer Substrates as Small Label-Free Real- Time Bioprobes, Nano Lett. 8, 2718 (2008).

11 Nanoplasmonic biosensors-limitations 1. Sensitivity (nm/riu), 2. Linewidth (nm), 3. Figure of merit (sensitivity/linewidth) 4. Resolution: bulk refractive index (unit: RIU) or surface mass density (pg/mm 2 ) Single-channel sensor Detection scheme Sample structure Resolution Reference Angular modulation Flat metal film (SPR) RIU Chem. Rev. 108, 462 (2008) Spectral modulation Nanohole arrays RIU ACS Nano 5, 6244 (2011) Spectral modulation Nanohole arrays RIU PNAS 103, (2006) Spectral modulation Nanohole arrays RIU Anal. Chem. 84, 1941 (2012) Intensity modulation Nanohole arrays RIU Opt. Express 19, (2011) Multi-channel sensor Sample structure Resolution Sensing spot size Reference Flat metal film (SPRi) RIU 100 ~ 500 μm Biomaterials 28, 2380 (2007) Nanohole arrays RIU 6 μm Anal. Chem. 81, 2854 (2009) Nanohole arrays RIU 1.5 μm J. Micromech. Microeng. 21, (2011) Nanohole arrays RIU 6 μm Biosens. Bioelectron. 24, 2334 (2009) Nanohole arrays RIU 5 μm Nano Lett. 8, 2718 (2008)

12 Nanoplasmonic biosensors Research challenges: 1. Develop low-cost single-channel plasmonic sensor using spectral modulation with performance comparable to commercial SPR systems. 2. Scale-up nanoplasmonic sensor arrays for high-throughput sensing with performance comparable to commercial SPR imagers, but using significantly smaller sensor footprint. Our approach: Nanoplasmonic interferometry Plasmonic architectures Interferometry Plasmonic Interferometer

13 Outline 1 Introduction Surface plasmon resonance (SPR) biosensors Nanoplasmonic biosensors 2 Plasmonic Mach-Zehnder interferometer for highly-sensitive biosensing Sensor design and fabrication Label-free, real-time biomolecular sensing 3 Plasmonic interferometers for array-based high-throughput sensing Scaling up plasmonic sensors for multiplexed sensing in imaging mode Imaging-based high-throughput sensing experiment 4 Optimization of plasmonic interferometers Design of circular plasmonic interferometer High-performance single-channel sensing High-performance imaging-based multiplexed sensing 5 Conclusions and future directions

14 Plasmonic Mach-Zehnder interferometer 1. Vertically aligned sensing and reference arms (small, compact MZI sensor footprint) 2. Simple, easy-to-fabricate nanostructure (doublet in a metal film) Silver film:350 nm thick Slit width:100 nm, length: 35 µm Silicon planar Mach-Zehnder interferometer: Modulator, switch, filter, biosensor (100 µm separation between arms) Gao et.al., Plasmonic Mach Zehnder interferometer for ultrasensitive on-chip biosensing, ACS Nano, 5, 9836 (2011).

15 Plasmonic nanosensor chip - Fabrication 1. E-beam evaporation of silver on glass substrate. 2. Focused ion beam milling 3. PECVD 4 nm SiO 2 as protection layer 4. Ellipsometer for characterization Silver film:350 nm thick Slit width:100 nm, length: 35 µm

16 Plasmonic nanosensor microfluidic chip fabrication Microfluidic channel: 50 μm height, 50 μm width

17 Plasmonic Mach-Zehnder interferometer 1. Sensitivity: 3600 nm/riu 2. Figure of merit: Further improvement possible Sensitivity: 178 nm/riu for nanoparticles, Nano Lett. 9, 4428 (2009) 300~560 nm/riu for nanoslit arrays, Nano lett. 9, 2584 (2009) 323 nm/riu for nanohole arrays, Nano Lett. 8, 2718 (2008) Figure of merit: 23 for nanohole arrays, Nat. Nanotech. 2, 549 (2007) typically < 10 for LSPR sensors, Chem. Rev. 111, 3828 (2011) 108 for prism-based SPR, Opt. Lett. 31, 1528 (2006) Gao et.al., Plasmonic mach zehnder interferometer for ultrasensitive on-chip biosensing, ACS Nano, 5, 9836 (2011).

18 Plasmonic Mach-Zehnder interferometer 300 nm SA 15 nm peak shift (Plasmonic MZI) 370 nm SA 3.8 nm, ACS Nano 5, 844 (2011) 370 nm SA 6 nm, SMALL 5, 1889 (2009) 2 µm SA 3 nm, Nano lett. 3, 935 (2003) Summary: 1. Record high sensitivity & sensing figure of merit, shows promise of this sensing technique. 2. First demonstration of biomolecular sensing using plasmonic interferometry. Limitations: The sensor structure is not currently suitable for high-throughput sensing. Gao et.al., Plasmonic mach zehnder interferometer for ultrasensitive on-chip biosensing, ACS Nano, 5, 9836 (2011).

19 Outline 1 Introduction Surface plasmon resonance (SPR) biosensors Nanoplasmonic biosensors 2 Plasmonic Mach-Zehnder interferometer for highly-sensitive biosensing Sensor design and fabrication Label-free, real-time biomolecular sensing 3 Plasmonic interferometers for array-based high-throughput sensing Scaling up plasmonic sensors for multiplexed sensing in imaging mode Imaging-based high-throughput sensing experiment 4 Optimization of plasmonic interferometers Design of circular plasmonic interferometer High-performance single-channel sensing High-performance imaging-based multiplexed sensing 5 Summary

20 Plasmonic interferometers for array-based sensing Silver film: 350 nm thick Slit width: 100 nm, length 30 µm Groove: 130 nm wide, depth 70 nm 1. Collinear transmission geometry 2. Still low interference contrast Gao et.al., Plasmonic interferometers for label-free multiplexed sensing, Opt. Express, 21, 5859 (2013).

21 Plasmonic interferometers for array-based sensing Scale bar: 10 µm Packing density: sensors per cm 2 Slit-groove plasmonic interferometers demonstrated for multiplexed sensing in imaging mode. Sensor resolution = RIU (close to commercial SPR imager: RIU) Sensor footprint: μm 2, (100X smaller than for commercial SPR imager) However, sensing performance needs further improvement. Gao et.al., Plasmonic interferometers for label-free multiplexed sensing, Opt. Express, 21, 5859 (2013).

22 Outline 1 Introduction Surface plasmon resonance (SPR) biosensors Nanoplasmonic biosensors 2 Plasmonic Mach-Zehnder interferometer for highly-sensitive biosensing Sensor design and fabrication Label-free, real-time biomolecular sensing 3 Plasmonic interferometers for array-based high-throughput sensing Scaling up plasmonic sensors for multiplexed sensing in imaging mode Imaging-based high-throughput sensing experiment 4 Optimization of plasmonic interferometers Design of circular plasmonic interferometer High-performance single-channel sensing High-performance imaging-based multiplexed sensing 5 Summary

23 Plasmonic nanosensor chip - Optimization Groove: R = 4.3 µm. w = 200 nm d = 45 nm P = 430 nm Hole: r = 310 nm 1. Collinear transmission setup 2. Circular design: balance SPPs and light in power - high interference contrast 3. Large interferometer array - high spectral S/N ratio Gao et.al., Plasmonic interferometric sensor arrays for high-performance label-free biomolecular detection, Lab Chip, 13, 4755 (2013).

24 Circular plasmonic interferometer array Experimentally demonstrated high interference contrast, intense transmission peak, narrow interference linewidth, and broadband sensor response Gao et.al., Plasmonic interferometric sensor arrays for high-performance label-free biomolecular detection, Lab Chip, 13, 4755 (2013).

25 Circular plasmonic interferometer array Broadband sensor response Multispectral sensing method Sensor resolution: RIU 2 IR I( ) I State-of-the-art nanohole array: 0( ) / I0( ), RIU, Gao et.al., Plasmonic interferometric sensor arrays for high-performance label-free biomolecular detection, Lab Chip, 13, 4755 (2013). H. Im et. Al., Anal. Chem 84, 1941 (2012)

26 Circular plasmonic interferometer array Resolution: 0.4 pg/mm 2 Commercial SPR : 0.1 pg/mm 2 1. Two orders of magnitude smaller sensor footprint (150 µm 150 µm). 2. Integration with compact microfluidics, decrease sample consumption. 3. Simple optical setup. Research goals: 1. To develop a single-channel plasmonic sensor using spectral modulation with performance comparable to commercial SPR systems. 2. To scale up the proposed sensor for high-throughput sensing with performance comparable to commercial SPR imagers, but using significantly smaller sensor footprint. Gao et.al., Plasmonic interferometric sensor arrays for high-performance label-free biomolecular detection, Lab Chip, 13, 4755 (2013). H. Im et. Al., Anal. Chem 84, 1941 (2012)

27 Circular plasmonic interferometer array optimization FOM* = (ΔI/I 0 ) /dn Record high FOM* = 147 Delicate balance between two interfering components - Low-background interferometric sensing Gao et.al., Plasmonic interferometric sensor arrays for high-performance label-free biomolecular detection, Lab Chip, 13, 4755 (2013). Plasmonics 5, 161 (2010)

28 Summary 1. We have demonstrated a plasmonic interferometric sensor for highly-sensitive single-channel sensing, with performance comparable to commercial SPR systems. 2. The proposed sensors were fabricated in a high-density array format for multiplexed sensing, with performance comparable to SPR imagers but using a two orders of magnitude sensor footprint. 3. The successful transformation of SPR technique from prism-coupling to this far simple optical setup would lead to major advances in low-cost, portable biomedical devices as well as in other highthroughput sensing applications including proteomics, diagnostics, drug discovery, and fundamental cell biology research.