Nanostructured Plasmonic Interferometers for Ultrasensitive Label-Free Biosensing
Fil BartoliLehigh University
4/9/2014
P.C. Rossin College of Engineering and Applied Science
Department of Electrical and Computer Engineering
Smith Family Laboratory for Optical Technologies
Lab Members:Qiaoqiang Gan (now at U Buffalo)Yongkang GanBeibei ZengZheming Xin
Collaborators:Prof. Xuanhong Cheng (MSE)Bu Wang
Outline1 Introduction
Surface plasmon resonance (SPR) biosensorsNanoplasmonic biosensors
2 Plasmonic Mach-Zehnder interferometer for highly-sensitive biosensingSensor design and fabricationLabel-free, real-time biomolecular sensing
3 Plasmonic interferometers for array-based high-throughput sensingScaling up plasmonic sensors for multiplexed sensing in imaging modeImaging-based high-throughput sensing experiment
4 Optimization of plasmonic interferometers Design of circular plasmonic interferometerHigh-performance single-channel sensingHigh-performance imaging-based multiplexed sensing
5 Summary
BiosensorsBiosensor applications: fundamental biological research, drug discovery, biomedicaldiagnostics, environmental monitoring, food testing, homeland security.
Global: 8.5 billion (2012) - 16.8 billion (2018)US:2.6 billion (2012) – largest market
“Biosensors - A Global Market Overview”, 2012A. G. Brolo, “Plasmonics for future biosensor”, Nature Photonics, 6, 709 (2012)
1. Fluorescent labeling
Time consumingInterfere with target molecules
2. Label-free detection
FastReal-timeNo labeling
SPR biosensors – working principle
http://www.biosensingusa.com/ http://www.biacore.com/
Underlying physics: the resonant excitation of surface plasmon polaritons (SPPs)
SPPs - Electromagnetic waves coupled to coherent charge oscillations at a metal-dielectric interface
ω
k
ω0
𝑘 = 𝜔𝑐 𝑘 = 𝜔
𝑐 𝑛 𝑠𝑖𝑛𝜃
𝑘 = 𝜔𝑐
𝑛 𝜀𝑛 + 𝜀
𝑛 𝑠𝑖𝑛𝜃 = 𝑘 =
SPR biosensors - advantage
http://www.biacore.com/
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.
SPR biosensors-Limitations
http://www.biacore.com/A. G. Brolo, “Plasmonics for future biosensor”, Nature Photonics, 6, 709 (2012)
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.
SPR biosensors-Limitations
http://www.microfl.com
2. Difficult to increase SPR Imaging throughput• Avoid crosstalk between sensing spots (large sensing spot size - 100-500 μm diam.)• No use of high NA optics for magnification to increase signal/noise ratio • Low throughput, not suitable for single-cell analysis
Nanoplasmonic biosensors
J-C Yang et. al., “Metallic Nanohole Arrays on Fluoropolymer Substrates as Small Label-Free Real-Time Bioprobes,” Nano Lett. 8, 2718 (2008). http://www.its.caltech.edu/~ahmet/publications.html
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
Nanoplasmonic biosensors-limitations1. Sensitivity (nm/RIU), 2. Linewidth (nm), 3. Figure of merit (sensitivity/linewidth)4. Resolution: bulk refractive index (unit: RIU) or surface mass density (pg/mm2)
Detection scheme Sample structure Resolution ReferenceAngular modulation Flat metal film (SPR) 1 × 10-7 RIU Chem. Rev. 108, 462 (2008)
Spectral modulation Nanohole arrays 2 × 10-5 RIU ACS Nano 5, 6244 (2011)
Spectral modulation Nanohole arrays 1 × 10-5 RIU PNAS 103, 17143 (2006)
Spectral modulation Nanohole arrays 3.1 × 10-6 RIU Anal. Chem. 84, 1941 (2012)
Intensity modulation Nanohole arrays 6.4 × 10-6 RIU Opt. Express 19, 15041 (2011)
Sample structure Resolution Sensing spot size ReferenceFlat metal film (SPRi) 1 × 10-5 RIU 100 ~ 500 μm Biomaterials 28, 2380 (2007)
Nanohole arrays 2 × 10-4 RIU 6 μm Anal. Chem. 81, 2854 (2009)
Nanohole arrays 2 × 10-4 RIU 1.5 μm J. Micromech. Microeng. 21, 115001 (2011)
Nanohole arrays 1 × 10-4 RIU 6 μm Biosens. Bioelectron. 24, 2334 (2009)
Nanohole arrays 1.5× 10-4 RIU 5 μm Nano Lett. 8, 2718 (2008)
Sing
le-c
hann
el se
nsor
Mul
ti-ch
anne
l sen
sor
Nanoplasmonic biosensors
Our approach: Nanoplasmonic interferometry
Plasmonic Interferometer
Interferometry
Plasmonic architectures
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 significantlysmaller sensor footprint.
Outline• 1 Introduction
Surface plasmon resonance (SPR) biosensorsNanoplasmonic biosensors
• 2 Plasmonic Mach-Zehnder interferometer for highly-sensitive biosensingSensor design and fabricationLabel-free, real-time biomolecular sensing
• 3 Plasmonic interferometers for array-based high-throughput sensingScaling up plasmonic sensors for multiplexed sensing in imaging modeImaging-based high-throughput sensing experiment
• 4 Optimization of plasmonic interferometers Design of circular plasmonic interferometerHigh-performance single-channel sensingHigh-performance imaging-based multiplexed sensing
• 5 Conclusions and future directions
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)
Gao et.al., “Plasmonic Mach–Zehnder interferometer for ultrasensitive on-chip biosensing,” ACS Nano, 5, 9836 (2011). http://nanob2a.cin2.es/
Silver film:350 nm thickSlit width:100 nm, length: 35 µm
Silicon planar Mach-Zehnder interferometer:Modulator, switch, filter, biosensor(100 µm separation between arms)
Plasmonic nanosensor chip - Fabrication
Silver film:350 nm thickSlit width:100 nm, length: 35 µm
1. E-beam evaporation of silver onglass substrate.
2. Focused ion beam milling3. PECVD – 4 nm SiO2 as protection
layer4. Ellipsometer for characterization
Plasmonic nanosensor microfluidic chip fabrication
Microfluidic channel: 50 μm height, 50 μm width
Plasmonic Mach-Zehnder interferometer
1. Sensitivity: 3600 nm/RIU2. Figure of merit: 1223. 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).
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)
Gao et.al., “Plasmonic mach–zehnder interferometer for ultrasensitive on-chip biosensing,” ACS Nano, 5, 9836 (2011).
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.
Outline• 1 Introduction
Surface plasmon resonance (SPR) biosensorsNanoplasmonic biosensors
• 2 Plasmonic Mach-Zehnder interferometer for highly-sensitive biosensingSensor design and fabricationLabel-free, real-time biomolecular sensing
• 3 Plasmonic interferometers for array-based high-throughput sensingScaling up plasmonic sensors for multiplexed sensing in imaging modeImaging-based high-throughput sensing experiment
• 4 Optimization of plasmonic interferometers Design of circular plasmonic interferometerHigh-performance single-channel sensingHigh-performance imaging-based multiplexed sensing
• 5 Summary
Plasmonic interferometers for array-based sensing
Gao et.al., “Plasmonic interferometers for label-free multiplexed sensing,”Opt. Express, 21, 5859 (2013).
Silver film: 350 nm thickSlit width: 100 nm, length 30 µmGroove: 130 nm wide, depth 70 nm
1. Collinear transmission geometry2. Still low interference contrast
Plasmonic interferometers for array-based sensing
Scale bar: 10 µmPacking density: 4 × 104 sensors per cm2
Gao et.al., “Plasmonic interferometers for label-free multiplexed sensing,”Opt. Express, 21, 5859 (2013).
Slit-groove plasmonic interferometers demonstrated for multiplexed sensing in imaging mode.• Sensor resolution = 5 × 10-5 RIU
(close to commercial SPR imager: 1 × 10-5 RIU)• Sensor footprint: 10 × 30 μm2,
(100X smaller than for commercial SPR imager)However, sensing performance needs further improvement.
Outline• 1 Introduction
Surface plasmon resonance (SPR) biosensorsNanoplasmonic biosensors
• 2 Plasmonic Mach-Zehnder interferometer for highly-sensitive biosensingSensor design and fabricationLabel-free, real-time biomolecular sensing
• 3 Plasmonic interferometers for array-based high-throughput sensingScaling up plasmonic sensors for multiplexed sensing in imaging modeImaging-based high-throughput sensing experiment
• 4 Optimization of plasmonic interferometers Design of circular plasmonic interferometerHigh-performance single-channel sensingHigh-performance imaging-based multiplexed sensing
• 5 Summary
Plasmonic nanosensor chip - Optimization
Gao et.al., “Plasmonic interferometric sensor arrays for high-performance label-free biomoleculardetection,”Lab Chip, 13, 4755 (2013).
Groove:R = 4.3 µm. w = 200 nm d = 45 nm P = 430 nm
Hole:r = 310 nm
1. Collinear transmission setup2. Circular design: balance SPPs and light in power - high interference contrast3. Large interferometer array - high spectral S/N ratio
Circular plasmonic interferometer array
Experimentally demonstrated high interference contrast, intense transmissionpeak, narrow interference linewidth, and broadband sensor response
Gao et.al., “Plasmonic interferometric sensor arrays for high-performance label-free biomoleculardetection,”Lab Chip, 13, 4755 (2013).
Circular plasmonic interferometer array
Broadband sensor response Multispectral sensing method Sensor resolution: 8 × 10-7 RIUState-of-the-art nanohole array:3 × 10-6 RIU,
� �2
10 0( ) ( ) / ( ) ,IR I I IO
OO O O �¦
Gao et.al., “Plasmonic interferometric sensor arrays for high-performance label-free biomoleculardetection,”Lab Chip, 13, 4755 (2013). H. Im et. Al., Anal. Chem 84, 1941 (2012)
Circular plasmonic interferometer array
Resolution: 0.4 pg/mm2
Commercial SPR : 0.1 pg/mm2
1. Two orders of magnitude smaller sensorfootprint (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 biomoleculardetection,”Lab Chip, 13, 4755 (2013). H. Im et. Al., Anal. Chem 84, 1941 (2012)
Circular plasmonic interferometer array optimization
Gao et.al., “Plasmonic interferometric sensor arrays for high-performance label-free biomoleculardetection,”Lab Chip, 13, 4755 (2013). Plasmonics 5, 161 (2010)
FOM* = (ΔI/I0) /dn
Record high FOM* = 147Delicate balance between two interfering components- Low-background interferometric sensing
Summary1. 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 high-throughput sensing applications including proteomics, diagnostics, drug discovery, and fundamental cell biology research.