Ghodssi R., Lin P., MEMS Materials and Processes Handbook

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944 P. Lin e t al.

the techniques include (i) treatment of silica or silicone surfaces by organosilanes,

(ii) treatment of noble metal surfaces (Au, Pt, Ag, etc.) by thiol or dialklydisulﬁde

compounds, and (iii) treatment of silicon or silicon nitride surfaces with alkenes.

Silanization of Silica or Silicone Surfaces

Organosilanes are commonly used in MEMS fabrication as adhesion promoters or

antistiction l ayers (see also Section 13.4.2). They can modify substrate surfaces such

as silica (e.g. glass, quartz) or silicone (e.g. PDMS) via the covalent Si-O-Si link-

age between organosilanes and the substrate surface. Although some silanol groups

(-SiOH) may originally exist on the PDMS surfaces, an O

plasma treatment on the

PDMS can produce more silanol groups for a more effective silanization reaction.

Examples of some commonly used organosilanes are shown in Fig. 13.7, which

include alkyl-substituted alkoxysilanes (1–6, 9) and alkyl-substituted chlorosilanes

(7, 8, 10, 11). Some chemicals in Fig. 13.7 (such as FOTS, No. 10) have similar

characteristics as those mentioned in Tables 13.1 and 13.2 (such as FDTS). FOTS

is commercially available for producing hydrophobic and non-stick surfaces using

a molecular vapor deposition tool (such as MVD-100, by Applied Microstructures).

The same tool can also be used to deposit self-assembled coatings based on APTMS

(No.3inFig.13.7), MAOPTS (No. 8), or MPTMS (No. 5) to enhance adhe-

sion, change hydrophobicity, and/or to create functional groups on the surface for

subsequent reactions. The organosilanes can be monofunctional, bifunctional, or

trifunctional, depending on the number of the silanol groups (Si-OH) that can be

converted upon hydrolysis (Fig. 13.8).

In general, coatings are more robust when organosilanes contain multi-

functional silyl groups. However, silanization involving trifunctional silyl groups

usually results in rougher surfaces because of the complex cross-linking reactions

(Fig. 13.9a). Silanization using organosilanes with monofunctional silyl groups

results in smoother surfaces (Fig. 13.9b), but they are more vulnerable to hydrolytic

desorption in a high-pH alkaline buffer.

Thiolation of Noble Metal Surfaces

As shown in Fig. 13.10, thiols or dialkyldisulﬁdes can be used to modify the surfaces

of noble metals such as Au, Ag, or Pt, to form self-assembled monolayers (SAMs)

[76, 77]. These modiﬁcations can yield excellent systems to study the interactions of

proteins with organic surfaces. Some examples of thiol compounds [76] and disul-

ﬁde compounds [77] are shown in Figs. 13.11 and 13.12, respectively. Typically,

to prepare SAMs on the surfaces of noble metals, a thiol or disulﬁde solution in

an organic solvent (e.g. ethanol or methanol) with a very dilute concentration, i.e.

0.2–20 mM, is prepared and then used to treat the surfaces of noble metals. SAMs

comprising mixtures of two or more components can also be prepared by chemisorp-

tion from solutions containing mixtures of these components [76]. Consequently, the

surface properties (e.g. hydrophobicity) can be tailored according to the ratio of the

different alkanethiolates on the modiﬁed surfaces.

13 Surface Treatment and Planarization 945

CO OCH

OCH

COCH

OCH

CCH

OCH

CO OCH

OCH

Cl Cl

CO OCH

OCH

OOC

CCH

OOC

Cl Cl

1234

567

8 91011

Fig. 13.7 Examples of organosilanes: (1) 3-aminopropyldimethylmethoxysilane, (2) 3-amino-

propylmethyldimethoxysilane, (3) 3-aminopropyltrimethoxysilane (APTMS), (4) 3-amino-

propyltriethoxysilane (APTES), (5) 3-mercaptotrimethoxysilane (MPTMS), (6) triethoxysi-

lylbutyraldehyde, (7) propyldimethylchlorosilane, (8) 3-methacryloxypropyltrichlorosilane

(MAOPTS), (9) 3-glycidoxypropyltrimethoxysilane (GPTMS), (10) 1H,1H,2H,2H-perﬂuoro-

octyltrichlorosilane (FOTS), and (11) octadecyltrichlorosilane

946 P. Lin e t al.

CO OCH

OCH

CO CH

OCH

CCH

OCH

Cl Cl

CCH

HO OH

HO CH

CCH

HO OH

CCH

Hydrolysis

Trifunctional

alkyl-substituted alkoxysilane

Bifunctional

alkyl-substituted alkoxysilane

Monofunctional

alkyl-substituted alkoxysilane

Trifunctional

alkyl-substituted chlorosilane

Monofunctional

alk

l-substituted chlorosilane

Fig. 13.8 Hydrolysis of organosilanes

Hydrosilylation of Silicon or Silicon Nitride Surfaces

Alkenes can be used to modify substrate materials based on single crystalline sil-

icon, porous silicon, or silicon nitride via Si-C bonding (Fig. 13.13)[78]. Prior

to hydrosilylation, the native SiO

layer on silicon must be removed (e.g. by

HF). Dilute (1–2%) HF solution treatment of a single crystalline Si (100) wafer

yields dihydride (-SiH

) on the surface, and a 40% NH

F solution treatment on Si

(111) results in monohydride (–SiH) groups. Similar etching treatments can also

be applied to silicon nitride substrates. For porous Si (created by electrochemical

HF etching), etching yields a –SiH

terminated silicon surface with x ranging from

1 to 3. The freshly prepared silicon hydride terminated surface is chemically homo-

geneous (>99% H terminated) and is a useful precursor because the Si-H bonds can

be further functionalized.

13 Surface Treatment and Planarization 947

CCH

OH O

CCH

OH O OH O

CCH

(A)

(B)

(

)

(

)

Fig. 13.9 A silica surface subjected to silanization treatment by (a) a trifunctional organosilane

and (b) a monofunctional organosilane

Hydrosilylation between C=C and Si-H can be started using radical initiators

such as diacyl peroxide at ~100

◦

C. However, thermally induced hydrosilyla-

tion of porous silicon at 110–180

◦

C, without initiators, has also been reported.

Alternatively, UV irradiation (185 and 253.7 nm wavelength UV light; 2 h) can

also be used to start hydrosilylation on the Si-H surface at room temperature. Some

examples of alkenes [78] are shown in Fig. 13.14.

13.5.3 Modiﬁcation of Pre-treated Substrate Surfaces

After the pristine surface has been modiﬁed using one of the methods described in

Section 13.5.2, the surface is either ready for use or requires further modiﬁcation. To

perform further modiﬁcation, the methods described in the previous section can still

be used. The modiﬁed surfaces may have exposed functional groups such as –OH,

-NH2, -COOH, -SH, or −CHO that are ready for further modiﬁcation. Therefore,

it is advantageous and convenient to exploit those chemical reactions for further

surface modiﬁcation in a multi-step procedure. The commonly employed chemical

reactions involving −OH, −NH

−COOH, −SH, and −CHO functional groups on

MEMS device surfaces for BioMEMS applications are summarized and elaborated

on in the sections that follow.

948 P. Lin e t al.

(A)

(B)

(C)

R’

M M

R’

Fig. 13.10 A noble metal

surface subjected to a

thiolation treatment by (a)a

thiol, (b)a

homodialkyldisulﬁde, and (c)

a heterodialkyldisulﬁde

SH SH

OCH

Fig. 13.11 Examples of thiols

13.5.3.1 Chemistry of Hydroxyl Groups (R-OH: Alcohols)

The chemical reaction shown in (13.3) allows an alcohol to form a covalent linkage

with another chemical compound containing an epoxy group.

13 Surface Treatment and Planarization 949

ROH

R’

(13.3)

EXAMPLE 4:

A three-step surface modiﬁcation process was used by Moorcroft et al. to modify

the PDMS substrate for in situ oligonucleotide synthesis on the surface of PDMS

microchannels [79]. First, PDMS channels were prepared by soft lithography using

SU-8 as a mold [80]. The PDMS was cured at room temperature overnight, and

then at 70

◦

C for 1 h. The PDMS channels were initially oxidized by an ozone

cleaner (UVO Cleaner



, by Jelight Co.). Secondly, vapor-phase silanization was

S S S

S S

Fig. 13.12 Examples of dialkyldisulﬁdes

(A)

RRR R R R R

Si Si Si Si Si Si Si

(B)

RRR

Si N N Si N N Si

Fig. 13.13 Hydrosilylation

of (a) a silicon surface and

(b) a silicon nitride surface

950 P. Lin e t al.

Fig. 13.14 Examples of alkenes

PDMS

(epoxysilanized PDMS)

OHHO

Fig. 13.15 Reaction of the hydroxyl group of HO-(C

-C

-OH with the epoxy group of

an epoxysilanized PDMS substrate, as described in Example 4 and reaction (13.3)

carried out in a vacuum oven with 3-glycidoxypropyltrimethoxysilane (GPTMS,

No. 9 in Fig. 13.7) to functionalize the substrate surface with epoxy groups. In

the third step of the surface modiﬁcation process (Fig. 13.15), the reaction (13.3)

was involved to create the covalent linkage between the surface-bound epoxy group

on the silanized PDMS substrate and the hydroxyl group of PEG spacer (HO-

(CH

OH). The oligonucleotides can be in situ synthesized on

the PEG surface using the conventional phosphoramidite chemistry with a DNA

synthesizer [79].

13.5.3.2 Chemistry of Amino Groups (R–NH

: Amines)

In this section, four different types of amine reactions are described, and each reac-

tion is accompanied by an example. The chemical reaction shown in (13.4) allows

13 Surface Treatment and Planarization 951

an amine to form a covalent linkage with another chemical species containing an

isothiocyanate group.

CSNR'

RNH

(13.4)

EXAMPLE 5:

A three-step surface modiﬁcation process was used by Charles et al. to fab-

ricate DNA chips for DNA hybridization efﬁciency studies [81]. First, the glass

substrates were acid-cleaned, and then the substrate was treated with a 2% acidic-

methanol solution of 3-aminopropyltriethoxysilane (APTES, No. 4 in Fig. 13.7).

In the second step of the surface modiﬁcation process (Fig. 13.16), the r eaction

(13.4) was used to generate the covalent linkage between the surface-bound amino

group (on APTES) and the isothiocyanate group of the bifunctional cross-linker,

1,4-phenylene diisothiocyanate (PDC). In the third step, the modiﬁed surfaces

(isothiocyanate groups) reacted with amine-modiﬁed single strand DNA molecules

(also shown in Fig. 13.16)[81].

A more popular chemical reaction (13.5) for an amine is to form a covalent

linkage with an isocyanate group. Aromatic isocyanates are more reactive than the

aliphatic isocyanates, and thus are more commonly used.

CONR'

RNH

(13.5)

Glass

ssDNA

NCS

(Aminosilanized Glass)–NH

Fig. 13.16 Reaction of the isothiocyanate group of 1,4-phenylene diisothiocyanate with the amino

group of an aminosilanized glass substrate, as described in Example 5 and reaction (13.4)

952 P. Lin e t al.

EXAMPLE 6:

A three-step surface modiﬁcation process was used by Jin et al. to fabricate

DNA chips for DNA hybridization efﬁciency studies [82]. Similarly to Example 5,

the silica surface was ﬁrst modiﬁed with 3-aminopropyltriethoxysilane (APTES, in

Fig. 13.7). This was performed by soaking the silica in 1 wt% (40 mM) APTES

solution in anhydrous toluene at room temperature for 30 min. In the second step

of the surface modiﬁcation process (Fig. 13.17), a maleimide-presenting surface

was generated using the reaction in (13.5). That is, the isocyanate group of the het-

erobifunctional cross-linker, p-maleimidophenyl isocyanate (PMPI), formed a urea

linkage with the APTES amines. The reaction was carried out in a 70 mM solution

of PMPI in anhydrous acetonitrile at room temperature for 30 min. The outermost

functional group became the maleimide group after this PMPI-APTES reaction.

The ﬁnal step was the immobilization of the thiol terminated DNA strands with

the surface maleimides.

The next example is the chemical reaction shown in (13.6), in which an amine

reacts with an N-hydroxysuccinimide ester (NHS-ester) to form an amide linkage.

RNH

R' R'

(13.6)

Glass

(Aminosilanized Glass)–NH

ssDNA

HS–(CH

)

NNCO

Fig. 13.17 Reaction of the amino group on an aminosilanized glass substrate with the isocyanate

group of p-maleimidophenyl isocyanate, as described in Example 6 and reaction (13.5).

13 Surface Treatment and Planarization 953

EXAMPLE 7:

Microﬂuidic channels made with PDMS (from SU-8 molds) and glass slides

were used to study the amyloid formation and ﬁbril growth [83]. Prior to bond-

ing, the glass slides were cleaned in piranha solution of 70% H

/30% H

(v/v) at 60

◦

C for 15 min. A three-step surface modiﬁcation process was used

to covalently attach the insulin molecules to the glass and PDMS walls of the

microchannels. First, the microchannels were injected with a 3% solution of APTES

in ethanol/water (95/5 by volume) for 1 h; then they were washed with ethanol and

cured at 100

◦

C. To activate the microchannel with N-hydroxysuccinimide (NHS)

ester, a solution of 20 mM N,N’-disuccinimidyl carbonate (DSC) in a sodium

bicarbonate buffer (50 mM, pH 8.5) was injected for 3 h at room temperature [83].

In the third step of the surface modiﬁcation process (Fig. 13.18), the reaction

(13.6) was involved to create covalent attachments between the amino group of

insulin molecules and the microchannel walls containing surface-bound NHS ester

groups. The insulin monomer solution was prepared by dissolving fresh insulin

(1 mg/mL) in 40 mM HCl solution to dissociate hexamers into monomers, and the

solution was ﬂushed through the microchannels for 10 min to covalently bond the

insulin monomers.

Glass

insulin

(Aminosilanized SiO

)

Fig. 13.18 Reaction of the amino group of an insulin molecule with the N-hydroxysuccinimide

ester group on an aminosilanized glass-based substrate, as described in Example 7 and reaction

(13.6)

The chemical reaction (13.7) allows an amine to form a covalent linkage with

another chemical species containing an epoxy group. This reaction is similar to reac-

tion (13.3), except that an amino group replaces the hydroxyl group in the reaction.

Both groups are commonly used for the ring opening reaction with the epoxy group

RNH

(13.7)