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Mike Thompson

Hydration of ultra-thin surface films and its role in enhancement of biocompatibility of medical devices. Mike Thompson Department of Chemistry and Institute for Biomaterials and Biomedical Engineering, University of Toronto

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Mike Thompson

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  1. Hydration of ultra-thin surface films and its role in enhancement of biocompatibility of medical devices Mike Thompson Department of Chemistry and Institute for Biomaterials and Biomedical Engineering, University of Toronto 9th Annual Conference on the Physics, Chemistry and Biology of Water Pamporovo, Bulgaria, October, 2014

  2. Topics • The core of our research – theranostics – combined therapy and detection • Fouling and the sensor–biological fluid interface • Link between fouling and biocompatibility • Anti-thrombotic surface chemistry • Role of surface hydration • Neutron reflectometry of ultra – thin film water • Anti-fouling / anti-thrombogenetic effect - concerted mechanism involving structured water • Questions

  3. The Challenges of Critical CareSick Patients Coagulopathy Shock Organ Failure Inflammation

  4. In-line theranostics and medical bypass circuitry

  5. Electromagnetic acoustic wave sensor

  6. Fouling of Quartz by Serum undiluted goat serum Sheikh, S.; Yang, D. Y.; Blaszykowski, C.; Thompson, M. Chem. Commun.2012, 48, 1305 12

  7. Surface Modifier Structure Y Functionalizable for subsequent biomolecule immobilization Head function Linkers for biosensors Alkyl: –(CH2)n– Oligoethylene glycol (OEG): –(O–CH2–CH2)n– Perfluoroalkyl: –(CF2)n– Backbone X Trichlorosilyl (Cl3Si), trialkoxysilyl ((RO)3Si), thiol (–SH), ... Anchoring function Quartz (piezoelectric), gold (electrical), stainless steel (implant), plastics (flexible), ... Substrate 5

  8. Systematic Structural Modification 1/1 (v/v) H2O/MeOH room temp., overnight 13 Sheikh, S.; Yang, D. Y.; Blaszykowski, C.; Thompson, M. Chem. Commun.2012, 48, 1305

  9. Antifouling Behaviour Through the use of structurally simple surface modifiers, the frequency shift due to the adsorption of goat serum was substantially reduced from ~ -31 kHz for bare quartz to less than -3 kHz for MEG-OH films Sheikh, S.; Yang, D. Y.; Blaszykowski, C.; Thompson, M. Chem. Commun.2012, 48, 1305 14

  10. BLOOD CONTACTING MEDICAL DEVICES Stents Extracorporeal Circuits P Pacemaker Blood Contacting Medical Devices Hemo-dialyzer Vascular Graft Econous Inc. July 2012

  11. Biosensors Group Blood interaction and bypass circuitry • Cardiopulmonary bypass (CPB) surgery is a common operation with • Over 1 million yearly worldwide1 • Has several undesired consequences including blood coagulation • After surgery complications can occur for 20% for low risk patients with 12% result in multi organ dysfunction • syndrome2 • Multi organ dysfunction syndrome has a mortality rate of 40%3 1. Sphere medical statistics 2. Grover FL: . Ann ThoracSurg 1999;68:367-373; discussion 374-376. 3. Kollef MH, Wragge T, Pasque C:. Chest 1995;107:1395-1401. IBBME

  12. Collagen Coated Polycarbonate surfaces

  13. MEG-OH coated Surfaces MEG-OH coated Surfaces

  14. Purpose of Research To investigate the hydration of ultra-thin films and gain insight into its anti – fouling mechanism. Bulk water • Probe water density of water at MEG-OH and OTS-OH adlayers (normal to the surface) • Examine interfacial water • Determine the effect of the internal ether oxygen atom on behaviour of water with adlayer Water density profile How? Neutron reflectometry MEG-OH OTS-OH

  15. Canadian Neutron Beam Centre (CNBC) • CNBC’s National Research Universal (NRU) Reactor • Neutrons produced via fission of 235U (D2O moderator) • Largest global producer of medical isotopes (60Co, 99Mo, 131I) • > 85% neutron time to users (universities, research facilities) • Applications: Structural chemistry, soft materials, thin films/interfaces (examples) Greetings from Chalk River! Ontario D3 Neutron Reflectometer • Neutron Reflectometry (NR) • A neutron diffraction technique probing the specular reflectivity of surfaces and buried interfaces in layered systems • Functions and Features • Structural and compositional information (e.g. oxide growth) • Atomic distribution (depth profiles) • High penetration depth • Film thickness (up to 200 nm) • Sensitive to 1H and 2H • Manipulation of contrast between media 6 Beam lines!!!

  16. NR Theory: Reflectivity Curve Anatomy Addition of layer (film) N+1 interfaces Amplitude αΔSLD 9.42 x 10-6 Å-2 3.00 x 10-6Å-2 2.07 x 10-6Å-2 Air d Cr Si • Kiessig fringes: Oscillations originate from constructive/destructive interference of reflected neutron waves • Frequency depends on thickness of the layer • Δq= 2π/d • Amplitude depends on contrast between adjacent media (ΔSLD) • - Enhanced sensitivity with increasing contrast Kiessig fringes z ks ko Period of oscillation 1/α layer thickness (d) θo θo j σj Surface Roughness x Dampened oscillations Diffuse scattering of neutrons ↓ R

  17. Measurements in CMW: Si/SiO2 MEG-OH Si/SiO2 OTS-OH • Fringes on MEG-OH, OTS-OH reflectivity curves confirm presence of a ‘layer’ between SiO2 and CMW (interference of reflected neutron wave) • MEG-OH: dampened oscillations (low amplitude) • OTS-OH : sharper minima, oscillations with higher amplitude • FIT REFLECTIVITY DATA WITH MODEL

  18. Measurements in CMW: Si/SiO2 Reflectivity + Fits SLD Profile: 2-Phase Fit Bulk Interfacial water SiO2 Film Low SLD (organic coating)

  19. “Water Barrier”? BULK - - - - - - - - - - - - - BULK INTERFACIAL WATER 22 Å - - - - - - - - - - - - - 4 Å 6 Å 5 Å quartz quartz MEG-OH OTS-OH not to scale 17

  20. Some questions • What is the origin of the myth that high quality SAMs reduce adsorption + fouling? • What is the precise role of the distal –OH in MEG-OH? • Why is the chemistry so “robust” in terms of antifouling / antithrombogenesis? • Can the surface chemistry lead to a quantum changes in medical device technology? • Does hydration play a role in biochemical interactive selectivity – e.g. cell signaling?

  21. Mike Thompson Research Group, October, 2014 Jack Sheng Jenise Chen Dr. Sonia Sheikh Niall Crawley Brian De La Franier Edmund Chan Elaine Chak Ellie Wong Kiril Fedorov Tairan Wang Pat Benvenuto RohanRavindranath Dr. Chris Blaszykowski Ruben Machado Dr. Larisa Cheran Miguel Neves Victor Crivianu-Gaita

  22. THANKS FOR LISTENING!mikethom@chem.utoronto.ca

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