Biomaterials for MEMS

Polymer-Based Biocompatible Surface Coatings 175

8.2.1.2 Electrostatic Adsorption

In this method, electrostatic adsorption of charged polymers on oppositely

charged surface was used for creating a non-fouling surface layers on metallic

surfaces.

46−48

Hubbell and Spencer developed a class of copolymers based on

poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), which was found to sponta-

neously adsorb from aqueous solution onto several metal oxide surfaces, pro-

viding a high degree of resistance to protein adsorption.

46−47

The adsorbed co-

polymer layer formed a comb-like structure on the surface, with positively charged

primary amine groups of the PLL bound to the negatively charged metal oxide

surface due to electrostatic interaction, while the hydrophilic and uncharged PEG

side chains were exposed to the solution phase. The resulting adsorbed layers were

highly effective in reducing the protein adsorption from both individual protein

solutions and blood serum. The amount of protein adsorbed from human serum

on the modified surfaces was consistently below 1–2 ng cm

−2

. Fibrinogen adsorp-

tion was reduced by 96-98% in comparison to the unmodified oxide surfaces.

8.2.2 Chemisorption of PEG Containing Thiol or Sulfide Groups

The spontaneous assembly of thiol or sulfide containing molecules on noble metal

surfaces is a good method for surface modification.

49

This method has been

extensivelyusedinthemodificationofgoldorgoldcoatedsurfaces.Onegreatad-

vantage of this method was the ease of preparation of surfaces; alkanethiols readily

assemble when gold surface was exposed to alkanethiols either in solution or

vapor phase.

49−50

Self assembled monolayers (SAMs) of alkanethiols, terminated

with short oligomers of the ethylene glycol groups, (HS(CH

2

)

11

-(OCH

2

CH

2

)

n

OH),

were developed to resist the adsorption of several model proteins.

51−59

Prime and Whitesides prepared monolayers from alkanethiols terminated

with short oligomers of the ethylene glycol group (HS(CH

2

)

11

(OCH

2

-CH

2

)

n

OH;

n= 3-7) and studied their protein exclusion behavior

51

They found that these

monolayers appeared to provide a general solution for controlling non-specific

adsorption of proteins with a range of molecular weights and isoelectric points

(pI), and under a wide range of solution conditions

52−53

For a better understanding of the factors involved in the protein resistance

of oligoether SAMs, Herrwerth and Grunze synthesized a series of oligoether-

terminated alkanethiols with different oligoether backbones, different chain

lengths and different alkyl terminals.

54−56

Their studies suggested that the pene-

tration of water molecules to the interior of the SAMs was a necessary prerequisite

for protein resistance. Three factors, including the hydrophilicity of the internal

units, packing density and the hydrophilicity of the terminal group should be

considered for making a non-fouling oligoether SAMs. It was demonstrated

that an interior hydrophilic structure was necessary as evident from the fact that

only the oligo(ethylene glycol) and oligo(trimethylene glycol) SAMs exhibited

protein resistance. Oligo(propylene glycol) SAMs did not show protein repelling

properties (Table 1). Another important factor was the packing density of SAMs.

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

Table 8. 1 AmountofadsorbedfibrinogenonSAMsongoldandsilver,mea-

sured by the ellipsometric thickness of the protein layer and normalized to the

amount of fibrinogen adsorbed on a monolayer of hexadecanethiol (C16SH) on

gold (=100%).

54

Protein Absorption[%] Protein Absorption[%]

Au Ag Au Ag

EG

1

OME(1) 22 57 EG

6

OMe(10) 0 35

EG

2

OH(2) 0 0 EG

6

OEt(11) 51 89

EG

2

OME(3) 0 62 EG

6

OPr(12) 69 100

EG

3

OH(4) 0 0 PRO

2

OMe(13) 52 87

EG

3

OME(5) 0 37 PRO

3

OMe(14) 49 80

EG

3

OEt(6) 60 88 PRO

4

OMe(15) 42 60

EG

3

Opr(7) 79 93 TRI

3

OH(16) 0 0

EG

3

OBu(8) 77 98 TRI

3

OMe(17) 0 52

EG

6

OH(9) 0 0

Figure 8.1. Amount of protein adsorption on a given oligoether SAM on gold normalized

to the amount of protein adsorbed on a monolayer of hexa-decanethiol on gold (100%)

versus advancing aqueous contact angle of the SAM. Symbols: red

,EG

2

OH; orange,

EG

3

OH; green+,EG

6

OH; blue,TRI

3

OH; blue ,EG

1

OMe; green,EG

2

OMe; light blue •,

EG

3

OMe; red ×,EG

6

OMe; blue ,TRI

3

OMe; red ×,PRO

2

OMe; blue♦,PRO

3

OMe; orange

+,PRO

4

OMe; purpl,EG

3

OEt; green◦,EG

6

OEt; blue,EG

3

OPr; green,EG

6

OPr; blue •,

EG

3

OBu. Images adapted from Ref. 54. For color reference, see page 270.

It was shown that SAMs with a relaxed lateral packing or with some defects or

disorder was required for high protein resistance. The methoxy-terminated SAMs

which form a highly ordered all-trans conformation lost non-fouling capacity due

to high packing densities. The terminal groups of the SAMs were shown to play

an equally important role (Fig. 8.1). For excellent protein resistance, the contact

angles should not exceed 70

◦

.

54

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