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Biosensing with Silicon Photonics

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Biosensing with Silicon Photonics Biosensing with silicon photonics Kristinn B. Gylfason KTH Micro and Nanosystems [email protected] KTH – Micro and Nanosystems IR cameras Transdermal drug delivery systems Silicon microneedles (www.flir.com) IR bolometer Photonic ring resonator biosensors RF filter Micro fuel cell (www.myfuelcell.se) RF switch Lab-on-a-Chip Polymer microfluidics Outline • Why do we need biosensors sensors? • Biosensor definition. • The fundamentals of photonic waveguide based biosensing • Silicon waveguides as biosensors. • Liquid sample handling for photonic biosensors. • Reducing temperature sensitivity. Why do we need biosensors? • When intruded by a disease causing virus or bacterium, the body releases biomolecules called antibodies into the blood. • The antibodies attach selectively to a part of the intruder called the antigen, to label it for attack by the immune system. • Accurate disease diagnosis requires the measurement of the concentration of these antibodies. • The concentration is very low (ng/ml), and there are other biomolecules in blood of much higher concentration (mg/ml). • By fixing an antigen on a biosensor surface, the attachment of antibodies can be measured with high selectivity. Image from Wikipedia More applications of biosensors • Medical diagnostics • Drug development • Explosives and narcotics detection • Environmental monitoring 6 Outline • Why do we need biosensors sensors? • Biosensor definition. • The fundamentals of photonic waveguide based biosensing • Silicon waveguides as biosensors. • Liquid sample handling for photonic biosensors. • Reducing temperature sensitivity. What are biosensors? Some commercial examples: • In general, biosensors are devices to characterize a chemical quantity: the analyte Attana QCM: www.attana.com Corning EPIC: www.corning.com • Biosensors can be used to: - Determine analyte concentration - Study the kinetics of chemical reactions of the analyte Biacore SPR: www.biacore.com Roche Accu-Chek: www.accu-chek.com 8 The formal definition of a biosensor For example: 1 Analytes: IUPAC definition: [K+] [Antibody] “A biosensor is a self-contained [Virus] integrated device which is [CO2] capable of providing selective Recognition: quantitative analytical DNA Antigen information using a biological recognition element which is in Enzyme direct spatial contact with a Transduction: QCM transducer element.” SPR EC 1 IUPAC: International Union of Pure and Applied chemistry 9 Analytes • Biosensors can be used to study: - Ions: K+, Cl-, Ca2+, … - Gasses: CO2, NH3, … - Sugars - Alcohols - Oligonucleotides (short single stranded DNA chains) - Various proteins and peptides: Antibodies, antigens - Viruses - and more … 10 Biological recognition elements Double stranded DNA • The fundamental idea of biosensing is using the work done by biological evolution to create highly selective biomolecular pairings. • Using one part of the pair as a recognition element allows selective measurement of the other part. • The biological recognition system provides selectivity and translates information from the biochemical domain (often an analyte concentration C) into chemical or physical output. • Biological recognition elements can be: - Oligonucleotides (short single stranded DNA chains) - Enzymes 11 - Antigens/Antibodies … Biological recognition elements Double stranded DNA • The biological binding reactions generally work only in water. • This is a serious limitation for biosensors that are adversely affected by the viscous damping of liquids. • For example: Resonating micromechanical cantilevers have shown mass detection limits of: - zeptograms (10-21) in vacuum [1] - but nanograms (10-9) in liquid [2] [1] Y. T. Yang, et al., Nano Letters 6, 583 (2006) [2] T. Braun, et al., Nature Nanotechnology 4, 179 (2009) 12 Transducer elements • The purpose of the transducer is to transform the output from the recognition system to a form suited for data analysis and storage (usually electrical). • Often the output of the recognition system is a mass change (∆m) or a charge change (∆q). • Most often these quantities are eventually translated to a frequency change (∆f) or a current change (∆i) of an electrical signal. • Complete biosensors can thus be described by their transduction chains. For example: ∆C ∆q ∆i or ∆C ∆m ∆f 13 Classification of biosensors Analyte Recognition Transduction Ions Enzymes Electrochemical Dissolved gasses Enzymes Electrochemical Vapors Antibodies Piezoelectric Receptor proteins Optical Substrates Enzymes Electrochemical (molecules upon Membrane receptors Piezoelectric which enzymes Whole cells Optical act) Plant or animal tissue Calorimetric Antibody/Antigen Antigen/Antibody Electrochemical Virus Piezoelectric Optical Surface plasmon Various proteins Receptor proteins Electrochemical Piezoelectric Optical Surface plasmon 14 Outline • Why do we need biosensors sensors? • Biosensor definition. • The fundamentals of photonic waveguide based biosensing • Silicon waveguides as biosensors. • Liquid sample handling for photonic biosensors. • Reducing temperature sensitivity. Interaction of light and matter: Wavelength change (refractive index) λ 0 Speed of light in vacuum: c Wavelength in vacuum: λ0 = c/f λꞌ nw In water light slows down to vꞌ Wavelength in water: λꞌ = vꞌ/f = λ0/nw λꞌꞌ ns Wavelength in a biomolecule solution: λꞌꞌ = λ0/ns < λꞌ n is the material's refractive index Waveguides for light control, by microfabrication Guided wave propagation Electric field (Ey) of the light wave in the A-A’ cross-section Evanescent field Liquid sample ns Core nc Bottom nb cladding λ = λ0/neff Effective refractive index of waveguide Evanescent field neff =f(nb, ns, nc) Evanescent field based biosensing with photonic waveguides Liquid sample Strength of evanescent field • Cross section along guide • Electric field of Anti- Y the propagating bodies light wave Antigens • Biomolecule binding Core Increased wg. effective Bottom index: cladding Δλ/λ = Δne/ne Photonic waveguide circuits for Δλ read out • The transduction chain of a photonic biosensor is: ∆C ∆m ∆n ∆λ Overlapping evanescent fields • We need to read out ∆λ. • Lithography enables fabrication of functional photonic circuits. • The directional coupler permits nearly lossless splitting and combining of light. Directional coupler Image from: http://www.comsol.com/wave-optics-module Ring resonators for Δλ read out Transmitted light to detector Light in at free space wavelength λ0 OnOff resonance resonance Transmitted m = 10 mλ /n = 2πR New light 0 e trans- to detector Surface binding mission spectrum Integermλ’0/n ’e = 2πR of ring fixed λ0 λ0 λ’0 Light in • Off resonance Most of light transmitted Directional coupler R=70 µm • On resonance Light coupled to ring Transmission minimum • Surface binding ne increase Light out Resonace wavel. increase: Δλ0 Ring resonator Ring resonator sensing fundamentals Input Pass Quality factor Volume Surface sensitivity sensitivity = = = The Q limits휆 the Resonance푉 wavelength휕휆 Resonance푆 wavelength휕휆 푄achievable shift per푆 refractive index unit shift for surface푆 density change sensor resolution.Δ휆 change of top 휕cladding.푛 of surface coating.휕휎 An example ring resonator biosensor chip Biosensor cartridge Ring resonator transducer 70 µm Antigen-Antibody pair 1 µm Light in Optical sensor array 750 µm Light out 24 C. F. Carlborg, K. B. Gylfason, et al., "A packaged optical slot-waveguide ring resonator sensor array for multiplex label-free assays in labs-on-chips," Lab Chip, vol. 10, pp. 281-290, Feb. 2010. Layout of sensor array optical circuit Grating coupling Waveguide Ring-resonator 25 Waveguide cross-section A-A’ Strip waveguide Slot waveguide Sample EvanescentΔnΔ waveσsp n s ΔσpΔλ Y Y Y Y Y Y Y Y Y Y Y Surface sensing Y Y Y nc Y Y ΔnsΔλ Waveguide IncreasedWaveguide light-analyte nb interaction Bottom cladding Volume sensing Time average of optical power through cross section (TE, λ=1310 nm) (TM, λ=1310 nm) Volume refractive index measurement of ethanol and methanol dilutions Limit of detection: noise level / sensitivity = 5 x 10-6 RIU State of the art refractometers: 10-8 RIU Selective surface bio-coating by spotting Spotting robot Chip spotted Spotts with BSA Spotting jets Biological recognition components Not spotted Spotted Bus Ring Precipitated salt crystals on surface Sensor M5 Sensor M6 Coupler 28 Biosensing (the antibody) (the antigen) C. F. Carlborg, K. B. Gylfason, et al. “A packaged optical slot-waveguide ring resonator sensor array for multiplex label-free assays in labs-on-chips,” Lab on a Chip, vol. 10, pp. 281-290, 2010. Outline • Why do we need biosensors sensors? • Biosensor definition. • The fundamentals of photonic waveguide based biosensing • Silicon waveguides as biosensors. • Liquid sample handling for photonic biosensors. • Reducing temperature sensitivity. Biosensing with silicon waveguides The high refractive index of silicon waveguides provide two benefits for sensing: 1. Rings can be made very small without reducing Q by bending loss, 2. The evanescent electric field at the silicon surface is very high, yielding high sensitivity for surface sensing. Biosensing with silicon waveguides Label-free detection limit of a few hundred molecules. K. De Vos, et al., "Silicon-on-Insulator microring resonator for sensitive and label-free biosensing," Optics Express, vol. 15, no. 12, pp. 7610-7615, 2007. Multiplexing K. De Vos, et al., "Multiplexed antibody detection with an array of Silicon-on-Insulator microring resonators," Photonics Journal, IEEE, vol. 1, no. 4, pp. 225-235, Oct.
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