Web Based Photonic Crystal Biosensors for Drug Discovery & Diagnostics

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1 Web Based Photonic Crystal Biosensors for Drug Discovery & Diagnostics Stephen C. Schulz

2 Introduction SRU Biosystems Inc., Woburn MA Biosensors, Instruments, Software, and Applications Drug Discovery and Diagnostic Applications Photonic Crystal Structures as Biosensors Label Free Binding / Mass Detection Fluorescent Label Amplification Component / Process Requirements Roll to Roll Biosensor Processing Future Direction Example 2

3 Drug Discovery and Diagnostic Applications Drug Discovery Label free binding assays. Screening for attachment of antibodies, small molecules, fragments to target proteins and cell receptors without fluorescent or radioactive labels. Diagnostics Amplified Fluorescence for pharmacogenomics. Screening patient genome for drug dosing or predicted efficacy. See recent FDA labeling change for Warfarin indicating the benefits of gene testing to guide dosing. 3

4 Photonic Crystal Subwavelength refractive index periodicity yields resonance. Steady state average field intensity - Ez 2 z-position (mm) Input field has magnitude E = 1 V/m 2D 2 x-position (mm) 1D Image contributions from Dr. Brian Cunningham at University of Illinois E z (V /m) 2 Above: Field intensity for one grating period. 4

5 Photonic Crystal Band Structure Measured 1 Wavelength (nm) PC Reflection Efficiency (%) q=~5 deg. Simulated Transmission % Resonance, characterized by high reflection, occurs at narrowly specified wavelengths and incidence angles Launch Angle (q degrees) 40 G-M Wavelength (nm) 750 Image contributions from Dr. Brian Cunningham at University of Illinois 5

6 Detecting Binding of Species to Sensor Surface. Assay Solution w/ Ligand (test species) Excitation Laser Fluorescent Amplification Mode Fluorescent Label Photonic Crystal Sensor Broadband Light Label Free Mode Optical Analogue to Quartz Xtal Monitor 6

7 Two Modes of Use for Sensing Molecular Binding Labeled Protein Spots on 2D Photonic Crystal Fluorescent Label Amplification Resonance Based Mass Sensor Label-Free Wavelength Shift Image On Spot 103 RFI (cts) Off Spot Image contributions from Dr. Brian Cunningham at University of Illinois 7

8 General Sensor Material Requirements Low / no background fluorescence. Materials near the sensor should have very low absorption, like laser mirrors. Absorbed light can reradiate at detectable wavelengths. Cyclic Olefin Polymers (COPs) have low fluorescence e.g. Zeanor or Topas. No birefringence. Sensor resonance is polarization specific. Can work around but increases material waste. Low / no extractable materials. Out gassing or leaching species can contaminate the assay and interfere with binding. Thick substrates, no stretching. 8

9 Basic Sensor Manufacturing Process Slit master roll. Dust and edge quality create issues down stream. Replicate. Create 3D structure on web substrate. Vacuum deposit optical thin film coatings. Cut sensors from roll. Bond sensors to rigid support in the form of standard labware. Curable and pressure sensitive adhesives. Cure state and solvent resistance important. Apply surface chemistry tailored to assay class. Surface chemistry links biological material to the sensor. Covalent protein attachment preferred. Package 1 year storage. 9

10 Photonic Crystal Replication Master Replication = Transfer of pattern to web substrate via UV cured material. 10

11 Nanostructured Sensors on Web 11

12 Vacuum Coating Requirements Optical thickness control equivalent to multi-layer AR coatings. Adhesion to polymers. Tape test. High rates. Film thickness 100 to 300 nm. Low absorption and scattering. Absorption leads to background fluorescence. Control of deposition profile. Maintain replicated features. Careful web handling to avoid damage to replicated features. Spectral monitoring of coating. Opportunities for surface functionalization on web. Examples : Epoxy or aledhyde surfaces for DNA or Protein binding. 12

13 Effects of vacuum coating process on Photonic Xtals Feature coverage by vacuum coatings affects sensor performance. >> Coating process may attack features. >> << Optical film composition affects sensor background. 13

14 Cut Sensors from Coated Roll Cut edge quality affects down stream processing. Scratches damage the sensor structure. 14

15 Bond Coupon to Standard Lab-ware Supports Use non water soluble adhesives with good solvent resistance. Packaging should not outgas volatiles. Labeling should provide trace ability. 15

16 Label Free Microplate / Reader Platform for Drug Discovery 16

17 Microfluidic-Sensor Integration at U of I Incorporate fluid delivery channels into replication pattern. Image contributions from Dr. Brian Cunningham at University of Illinois 17

18 Conclusions Web based photonic crystal devices have a prosperous commercial future and plenty of technical room to grow. 18

19 Acknowledgements Sensor Development Team at SRU Biosystems Inc. Kurt Albertson, Brenda Hugh, Frank Jackson, Wendy Montanez, Maneesha Dond, Michelle Kearns, Irina Rasputnis Brian Cunningham, Nano Sensors Group at the University of Illinois at Urbana-Champaign 19