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
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
The Challenges of Critical Care
Sick Patients
Coagulopathy
Inflammation
Shock
Organ Failure
In-line theranostics and medical
bypass circuitry
Electromagnetic acoustic wave
sensor
Fouling of Quartz by Serum
undiluted goat serum
Sheikh, S.; Yang, D. Y.; Blaszykowski, C.; Thompson, M. Chem. Commun. 2012, 48, 1305
12
Surface Modifier Structure
Head function
Y
Functionalizable for subsequent
biomolecule immobilization
Linkers for
biosensors
Alkyl: –(CH2)n–
Oligoethylene glycol (OEG): –(O–CH2–CH2)n–
Backbone
Perfluoroalkyl: –(CF2)n–
Anchoring function
Substrate
X
Trichlorosilyl (Cl3Si), trialkoxysilyl ((RO)3Si), thiol (–SH), ...
Quartz (piezoelectric), gold (electrical), stainless steel
(implant), plastics (flexible), ...
5
Systematic Structural Modification
1/1 (v/v) H2O/MeOH
room temp., overnight
Sheikh, S.; Yang, D. Y.; Blaszykowski, C.; Thompson, M. Chem. Commun. 2012, 48, 1305
13
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
BLOOD CONTACTING MEDICAL DEVICES
Stents
Extracor
poreal
Circuits
Pacemaker
P
Blood
Contacting
Medical
Devices
Vascular
Graft
Hemodialyzer
Econous Inc. July 2012
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
IBBME
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
Collagen Coated Polycarbonate surfaces
MEG-OH coated
Surfaces
Bulk water
Water density profile
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
How?
Neutron reflectometry
MEG-OH OTS-OH
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)
Neutron Reflectometry (NR)
D3 Neutron Reflectometer
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!!!
Amplitude α
ΔSLD
Addition of layer (film)
9.42 x 10-6 Å-2
3.00 x 10-6 Å-2
2.07 x 10-6 Å-2
N+1 interfaces
Air
Cr
d
Si
Kiessig fringes
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)
Surface
Roughness
z
ks
ko
x
θo
θo
j
σj
Dampened
oscillations
Diffuse scattering of neutrons ↓ R
Si/SiO2
MEG-OH
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
Reflectivity + Fits
SLD Profile: 2-Phase Fit
SiO2
Film Interfacial water
Bulk
Low SLD
(organic coating
Sample
SLDSiO2
(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
“Water Barrier”?
BULK
-------------
H
H
O
H
O
H
H H
H
O
H
H
H
H
O
O
H
H
O
H
H
H
O
H
H
H
O
H
H
O
H
4Å
H
H
H
H
O
H
H
Si
Si
O
O
H
not to scale
O
O
Si
O
O
H
O
O
O
O
6Å
5Å
O
Si
O
O
O
H
O
O
O
H
H
H
O
O
O
H
O
H
O
O
H
H
H
H
H
-------------
O
O
22 Å
O
H
H
H
H
INTERFACIAL
WATER
H H
O
O
H
O
H
O
H
O
O
H
O
O
H
H
O
O
H
H H
O
H
H
O
H
H
O
H
H
H
O
H
O
O
BULK
O
Si
O
O
Si
O
O
Si
O
O
Si
O
O
Si
O
O
quartz
quartz
MEG-OH
OTS-OH
Si
O
O
17
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?
Mike Thompson Research
Group, October, 2014
Jack Sheng
Dr. Sonia Sheikh
Brian De La Franier
Elaine Chak
Kiril Fedorov
Pat Benvenuto
Dr. Chris Blaszykowski
Dr. Larisa Cheran
Victor Crivianu-Gaita
Jenise Chen
Niall Crawley
Edmund Chan
Ellie Wong
Tairan Wang
Rohan Ravindranath
Ruben Machado
Miguel Neves
THANKS FOR LISTENING!
mikethom@chem.utoronto.ca