Biomaterials for MEMS

178 K.Yu,G.GaoandJ.N.Kizhakkedathu

Figure 8.2. High-resolution S2p X-ray photoelectron spectra (in counts per second).

These spectra are for CH

3

(CH

2

)

1

7SH (1-octadecanethiol), HOCH

2

(CH

2

)

10

SH (mercapto-1-

undecanol),and HOOC(CH

2

)

10

SH (11-mercaptoundecanoic acid) exposed to ambient en-

vironmental conditions (fresh, 5 days, 11 days) and PEG-bl-PPS-bl-PEG (fresh, 5 days,

41 days and exposed to ultraviolet and ozone).Spectra comprise doublet structures due to

the presence of the S

2p3/2

and S

2p1/2

peaks. In less than 2 weeks, thiols show significant

oxidation, whereas the PEG-bl-PPS-bl-PEG only shows nominal oxidation near 6 weeks.

The sample treated with ultraviolet and ozone demonstrates shifted oxidized S

2p

spectra as

positive control. Inset indicates chemical structure for PEG-bl-PPS-bl-PEG. Images adapted

from Ref. 65.

Bearinger et al. explored an alternative structure to alkanethiolates, namely

block copolymers comprising sulphides in a chemisorbing block (PEG

17

−

b−PPS

25

− b−PEG

9

) where PPS = polypropylene sulfide, in an expectation of

better resistance to oxidative instability.

65

These materials offer a more robust

approach to passivate gold surfaces against protein adsorption and cell adhesion.

The copolymer PEG

17

− b−PPS

25

− b −PEG

9

chemisorbed to form a 2.2 nm dense

monolayer of 226 ± 26 ng cm

-

2

. The copolymeric monolayer was much more stable

to oxidation than commonly used alkanethiolates (Fig. 8.2). Protein adsorption

was greatly reduced (>95%), even when exposed to whole blood serum (>55 mg

ml

-

1

protein concentration). The cell adhesion was also reduced over long culture

durations (> 97%) (Fig. 8.3). These results such that polysulphides containing

copolymers are attractive alternatives to alkanethiolates with greater stability and

allows greater flexibility in the design.

8.2.3 Covalent Grafting of Poly (ethyelene glycol)

Compared to oligo(ethylene glycol) SAMs, grafting of preformed poly(ethylene

glycol) (PEG) provided more robust films and versatile architecture, and chemistry

for the development of non-fouling surfaces. Several approaches have been

reported for grafting PEG chains on solid surfaces such as metal, silicon, plastics

to improve the biocompatibility relying on different coupling chemistry or tech-

niques.

Unsworth and Brash used chain-end thiolated PEO assemblies to investigate

the effect of PEO chain density on protein adsorption.

72

Their study showed that

resistance to fibrinogen adsorption for 750 and 2000 MW (molecular weight) PEO

layers increased with graft density of PEO chains and the least protein adsorption

was observed at ∼0.5 chains/nm

2

. However, the protein adsorption increased

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Polymer-Based Biocompatible Surface Coatings 179

Figure 8.3. Surface plasmon resonance measurements. a, Intensity of reflected light

against angle of incidence before and after deposition of PEG-bl-PPS-bl-PEG in methanol

on a gold surface. Polymer adsorption induces a shift of the resonance angle,which is

proportional to adsorbed mass. b, Shift of resonance angle observed in methanol as a

function of time by monitoring the increase of reflectivity at about 1

◦

gbelow the resonance

angle.c,Intensity of reflected light against time for serum addition, followed by subse-

quent buffer wash, on PEG-bl-PPS-bl-PEG-coated gold surface.d , Intensity of reflected light

against time for serum addition, followed by subsequent buffer wash, on gold surface. The

chain density and architecture are two important factors which influence the anti-fouling

properties. Images adapted from Ref. 65.

when the graft density was increased beyond 0.5 chains/nm

2

. For 5000 MW PEO,

the optimal chain density was found to be 0.5 chains/nm

2

.Brashet al. suggested

that at high chain density, the chemisorbed PEO was dehydrated giving a surface

that was no longer protein resistant.

Sofia et al. tested surfaces covalently grafted with poly(ethylene oxide) poly-

mers with different architecture, in linear and star form, on silicon membrane to

determine their ability to prevent protein adsorption.

73

Modified surfaces were

exposed to solutions of each of three proteins: cytochrome-c, albumin, and fi-

bronectin. It was found that protein adsorption decreased almost exponentially

with graft density of chains and it reached almost negligible adsorption at the

highest grafting densities. In contrast to surfaces grafted with linear PEG, star

PEG-grafted surfaces can prevent adsorption of larger proteins even though open

spaces existed between bound molecules. The adsorption was prevented as long

as the open spaces were smaller than the effective size of the protein. They

also proposed a physical model of the surface to explain the protein adsorption

resistance in terms of the spacing and degree of overlap of grafted PEO chains

which lead to steric repulsion between surface and protein. In the case of linear

PEG surfaces, a complete coverage of the surfaces with grafted polymer (chains

were roughly half-overlapping (i.e., L ≈ R

G

linear; Rg = radius of gyration, L-

distance between the grafting point)) was important for the prevention of protein

adsorption. Since the star PEO-grafted surfaces have much more polymer segment

concentration than linear chains of equivalent molecular weight or equivalent size

(Fig. 8.4), they prevented the adsorption of proteins to surface more efficiently.

Zhu et al. reported a strategy for the formation of uniform and ultra-flat

PEG monolayers on the atomically flat Si(111) surface with high grafting density

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