hydration of ultra-thin surface films and its role in enhancement of biocompatibility of medical...
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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
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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
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The Challenges of Critical CareSick Patients
Coagulopathy
Inflammation Organ Failure
Shock
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In-line theranostics and medical bypass circuitry
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Electromagnetic acoustic wave sensor
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Fouling of Quartz by Serum
Sheikh, S.; Yang, D. Y.; Blaszykowski, C.; Thompson, M. Chem. Commun. 2012, 48, 1305
undiluted goat serum
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Surface Modifier Structure
Anchoring function
Head function
Backbone
Substrate Quartz (piezoelectric), gold (electrical), stainless steel (implant), plastics (flexible), ...
Trichlorosilyl (Cl3Si), trialkoxysilyl ((RO)3Si), thiol (–SH), ...
Alkyl: –(CH2)n–
Oligoethylene glycol (OEG): –(O–CH2–CH2)n–
Perfluoroalkyl: –(CF2)n–
Functionalizable for subsequent biomolecule immobilization
X
Y Linkers for biosensors
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Systematic Structural Modification
Sheikh, S.; Yang, D. Y.; Blaszykowski, C.; Thompson, M. Chem. Commun. 2012, 48, 1305
1/1 (v/v) H2O/MeOHroom temp., overnight
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Antifouling Behaviour
Sheikh, S.; Yang, D. Y.; Blaszykowski, C.; Thompson, M. Chem. Commun. 2012, 48, 1305
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
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BLOOD CONTACTING MEDICAL DEVICES
Blood Contacting
Medical Devices
Vascular Graft
Hemo-dialyzer
PPacemaker
Stents
Extracorporeal Circuits
Econous Inc. July 2012
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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 Thorac Surg 1999;68:367-373; discussion 374-376.3. Kollef MH, Wragge T, Pasque C:. Chest 1995;107:1395-1401.
Biosensors Group IBBME
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Collagen Coated Polycarbonate surfaces
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MEG-OH coated Surfaces MEG-OH coated Surfaces
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To investigate the hydration of ultra-thin films and gain insight into its anti – fouling mechanism.
1) Probe water density of water at MEG-OH and OTS-OH adlayers (normal to the surface)
‒ Examine interfacial water
2) Determine the effect of the internal ether oxygen atom on behaviour of water with adlayer
Bulk water
SiO
O n
Quartz
O
O
SiO
O n
H
O
H
Quartz
Wat
er d
ensi
ty p
rofil
e
MEG-OH OTS-OH
How?Neutron reflectometry
Purpose of Research
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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)
Canadian Neutron Beam Centre (CNBC)
Greetings from Chalk River!
D3 Neutron Reflectometer
6 Beam lines!!!
Ontario
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
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NR Theory: Reflectivity Curve Anatomy
Addition of layer (film)N+1 interfaces
dCr
Air
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
Period of oscillation 1/α layer thickness (d)
Kiessig fringes
Amplitude α ΔSLD
9.42 x 10-6 Å-2
3.00 x 10-6 Å-2
2.07 x 10-6 Å-2
Dampened oscillations
z
σjj
koks
θo
θox
Surface Roughness
Diffuse scattering of neutrons ↓ R
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Measurements in CMW: Si/SiO2
MEG-OH
OTS-OH
Si/SiO2
• 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
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Measurements in CMW: Si/SiO2
SLD Profile: 2-Phase Fit
SiO2 Interfacial water BulkFilm
Reflectivity + Fits
SampleSLDSiO2
(x 10-6 Å-2)σSiO2 (Å)
d1
(Å)SLD1
(x 10-6 Å-2)SLDB
(x 10-6 Å-2)σB
(Å)
MEG-OH 3.67 14.3 21.7 2.97 3.66 16.5
OTS-OH 3.56 9.7 18.7 0.90 3.53 1.6
Low SLD(organic coating)
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“Water Barrier”?
Si
O
O
H
OO O
Si
O
O
H
OO
Si
O
O
H
OO
Si
O
O
H
O
O
H
HO
H
H
OH
H
O
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
H
O
H
HO H
HO
H H O
H
H
O
H
HO
H
H
O
H
HO
H
H
O
H
H
OH H
OH
H
quartz
17MEG-OH
Si
O
O
H
OO O
Si
O
O
H
OO
Si
O
O
H
O
Si
O
H
OO O
Si
O
H
OO
Si
O
H
O
quartz
OTS-OH
6 Å
22 Å
BULK
BULK
5 Å
4 Å
- - - - - - - - - - - - -
- - - - - - - - - - - - -
not to scale
INTERFACIALWATER
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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?
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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 Rohan Ravindranath
Dr. Chris Blaszykowski Ruben Machado
Dr. Larisa Cheran Miguel Neves Victor Crivianu-Gaita
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THANKS FOR [email protected]