Ac0346712-Solvent Compatibility of Pdms

Solvent Compatibility ofPoly(dimethylsiloxane)-Based Microfluidic Devices

Jessamine Ng Lee, Cheolmin Park,

†

and George M. Whitesides*

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138

This paper describes the compatibility of poly(dimethyl-siloxane) (PDMS) with organic solvents; this compatibilityis important in considering the potential of PDMS-basedmicrofluidic devices in a number of applications, includ-ing that of microreactors for organic reactions. We con-sidered three aspects of compatibility: the swelling of PDMS in a solvent, the partitioning of solutes between asolvent and PDMS, and the dissolution of PDMS oligo-mers in a solvent. Of these three parameters that deter-mine the compatibility of PDMS with a solvent, theswelling of PDMS had the greatest influence. Experimen-tal measurements of swelling were correlated with thesolubility parameter,

δ

(cal

1/ 2

cm

-

3/ 2

), which is based onthe cohesive energy densities,

c

(cal/ cm

3

), of the materi-als. Solvents that swelled PDMS the least included water,nitromethane, dimethyl sulfoxide, ethylene glycol, per-fluorotributylamine, perfluorodecalin, acetonitrile, andpropylene carbonate; solvents that swelled PDMS themost were diisopropylamine, triethylamine, pentane, andxylenes. Highly swelling solvents were useful for extractingcontaminants from bulk PDMS and for changing thesurface properties of PDMS. The feasibility of performingorganic reactions in PDMS was demonstrated by perform-ing a Diels

-

Alder reaction in a microchannel.

Several characteristics make poly(dimethylsiloxane) (PDMS)useful in fabricating microfluidic devices intended for bioanaly-sis: ease offabrication (rapid prototyping, sealing, interfacing withthe user), transparency in the UV

-

visible regions, chemicalinertness, low polarity, low electrical conductivity, and elasticity.

1,2

PDMS does not swell in contact with water. The cost offabricationin PDMS is low compared to that for many materials (e.g., glassor silicon) commonly used in microdevices and MEMs.

3

There is a growing interest in using microfluidic systems forfunctions other than bioanalysis in water, including organicsynthesis in organic solvents.

4

-

6

PDMS swells in contact withnonpolar solvents (e.g., hydrocarbons, toluene, and dichloro-methane) and is not useful for manipulations requiring thesesolvents. The objective of this work was to define the solventcompatibility of PDMS as a first step in discerning what types of solvents (other than water) can be used in microfluidic systemsfabricated in this material. It is clear that PDMS is not a universalmaterial and that other classes ofpolymers (or perhaps even glass,despite the inconvenience of fabricating devices in rigid, brittlematerials) will be required for non-and less-polar solvents. Whatare not clear are the characteristics of the solvents that arerequired for a solvent to be compatible with PDMS.The problem of solvent compatibility has three aspects: (1)the solubility ofa solvent in PDMS, since this solubility influencesthe swelling of the PDMS; (2) the solubility of solutes in PDMS(or more properly, the partition of solute between a solution andPDMS), since loss of solute from the solvent is a concern; and(3) the dissolution of PDMS oligomers in solvent, since theseoligomers (present as contaminants in cross-linked PDMS) arepotential contaminants in the products of reactions carried out inPDMS.

Background on Solubility.

Many parameters have been usedin calculating solubilities.

7,8

We have arbitrarily chosen to usecohesive energy density,

c

(cal/ cm

3

), the energy associated withthe intermolecular attractive interactions within a unit volume of material.

8

-

10

The cohesive energy density can be expressed as

c

) -

U/V,

where

U

is the molar internal energy (cal/ mol) and

V

is the molar volume (cm

3

/ mol). For two materials to be soluble,their cohesive energy densities must be similar, since this energymust be overcome to separate the molecules ofthe solute to allowthe molecules of solvent to insert. For materials such as cross-linked polymers that do not dissolve, solubility is measured bythe degree of swelling. The cohesive energy density is oftenexpressed in terms of the solubility parameter, or Hildebrandvalue:

δ

)

c

1/ 2

)

(

-

U/V

)

1/ 2

(cal

1/ 2

cm

-

3/ 2

).

8,11

The solubilityparameter is useful for predicting the swelling behavior of apolymer in a solvent without knowing any other information aboutthe solvent.

* Corresponding author. Phone: 617-495-9430. Fax: 617-495-9857. E-mail:gwhitesides@gmwgroup.harvard.edu.

†

Current address: Department of Metallurgical System Engineering, YonseiUniversity, Seoul, 120-749, Korea.(1) McDonald, J. C.; Whitesides, G. M.

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2002

,

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3473.(3) Becker, H.; Locascio, L. E.

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287.(4) Salimi-Moosavi, H.; Tang, T.; Harrison, D. J.

J. Am. Chem. Soc.

1997

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119

,8716

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8717.(5) Kakuta, M., Bessoth, F. G.; Manz, A.

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2001

,

1

, 395

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405.(6) Tokeshi, M.; Minagawa, T.; Uchiyama, K.; Hibara, A.; Sato, K.; Hisamoto,H.; Kitamori, T.

Anal. Chem.

2002

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74

, 1565

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1571.(7) Burke, J.

AIC Book Pap. Group Annu.

1984

,

3

, 13

-

58.(8) Du, Y.; Xue, Y.; Frisch, H. L.

Physical Properties of Polymers Handbook

; AIPPress: Woodbury, NY, 1996.(9) Mark, J. E.; Eisenberg, A.; Graessley, W. W.; Mandelkern, L.; Koenig, J. L.

Physical Properties of Polymers

; American Chemical Society: WashingtonDC, 1984.(10) Abboud, J.-L. M.; Notario, R.

Pure Appl. Chem.

1999

,

71

, 645

-

718.(11) The units for

δ

can be expressed as the square root of the cohesive energydensity (cal

1/ 2

cm

-

3/ 2

) or as the square root of a pressure (MPa

1/ 2

), where1 cal

1/ 2

cm

-

3/ 2

)

0.488 88 MPa

1/ 2

.

Anal. Chem.

2003,

75,

6544

-

6554

6544

Analytical Chemistry, Vol. 75, No. 23, December 1, 2003

For a binary system, the Hildebrand

-

Scatchard equationrelates the solubility parameters ofnonpolar liquids to the enthalpychange on mixing them:

∆

H

m

)

V

m

(

δ

1

-

δ

2

)

2

φ

1

φ

2

, where

V

m

isthe volume of the mixture,

δ

i

is the solubility parameter of thecomponent i, and

φ

i

is the volume fraction of i in the mixture.

8

For two components to be soluble in one another (i.e., for swellingto occur in a polymer

-

solvent system), the free energy of mixingmust be favorable, that is,

∆

G

m

<

0. Since

∆

G

m

)

∆

H

m

-

T

∆

S

m

,and

∆

H

m

∝

(

δ

p

-

δ

s

)

2

, swelling is maximal when (

δ

p

-

δ

s

)

2

is 0,where

δ

p

and

δ

s

are the solubility parameters of the polymer andsolvent.

8

Table 1 shows values of

δ

for a range of solvents often used inorganic synthesis.

8,10,12

Although the Hildebrand

-

Scatchard equa-tion suggests that solvents with

δ

similar to that of PDMS (

δ

)

7.3 cal

1/ 2

cm

-

3/ 2

) will swell PDMS effectively, the relationshipbetween

δ

and swelling is not linear and differs for each polymer

-

solvent system. We therefore wished to calibrate this rankingexperimentally. Many research groups have used gravimetricmethods to determine the degree of swelling of a polymer by asolvent.

13

-

17

The degree of swelling is measured by the ratio of the mass of the swollen network and solvent combined to themass of the dry extracted solid. This method has two majordisadvantages. First, the mass of the combined swollen network and solvent must be measured while in equilibrium with thesolvent in the vapor phase, so that evaporation ofthe solvent doesnot effect the measurement. Second, the gravimetric techniquerequires extra steps in its protocol compared to length measure-ments (described below), because the unpolymerized PDMSoligomers must first be extracted before measurement. In thisresearch, we measured swelling by placing a solid piece ofPDMSin a solvent for 24 h and then measuring the change in dimensions(e.g., length) of the solid while the PDMS was still submersed inthe solvent in the liquid phase. The amount of un-cross-linkedoligomers in solid PDMS is small (

∼

0

-

5%, w/ w; see laterdiscussion) compared to the cross-linked network, and theoligomers do not significantly affect the shape or length of thecross-linked PDMS. We, therefore, did not need to extract theoligomers from the PDMS before measuring the swollen length.The degree of swelling is expressed by the swelling ratio:

9,18

S

)

D

/

D

0

, where

D

is the length of the solid PDMS in the solventand

D

0

is the length of the dry, solid PDMS.

19

RESULTS AND DISCUSSION

Swelling of PDMS in Organic Solvents

.

Prediction of swelling of PDMS by a solvent is important when consideringwhich solvents to use in performing organic syntheses in micro-fluidic devices made in PDMS, which cosolvents to use inseparations, or which nonpolar components to expect to lose fromaqueous solution by contact with PDMS. Swelling of micro-channels has many implications. Swelling changes the cross-sectional area of the channel and, therefore, the rate and profileofflow. Changes in channel dimensions due to swelling can effectintegration of the channel with components such as membranes,detectors, mixers, or electrodes. Swelling also changes surfaceproperties and may cause the microfluidic device to deseal if thePDMS is bonded to a glass substrate.Here, we calibrate the relation of the solubility parameter,

δ

,ofeach solvent listed in Table 1 to the extent ofswelling ofPDMS.The degree ofswelling is measured by the swelling ratio,

S

; Table1 also reports the values ofthese ratios. Figure 1 plots the swellingratio observed for each solvent against its solubility parameter.The inset lists the solvents in descending order of solubility inPDMS.

20

As expected, solvents that have a solubility parametersimilar to that of PDMS (

δ

)

7.3 cal

1/ 2

cm

-

3/ 2

) generally swellPDMS more than solvents that have a solubility parameter

(12) Lide, D. R. In

Handbook of Chemistry and Physics

, 74th ed

.

; Lide, D. R., Ed.;CRC Press: Boca Raton, FL, 1994.(13) Favre, E.

Eur. Polym. J.

1996

,

32

, 1183

-

1188.(14) Yoo, J. S.; Kim, S. J.; Choi, J. S.

J. Chem. Eng. Data

1999

,

44

, 16

-

22.(15) Horkay, F.; Waldron, W. K.; McKenna, G. B.

Polymer

1995

,

36

, 4525

-

4527.(16) Hedden, R. C.; Wong, C.; Cohen, C.

Macromolecules

1999

,

32

, 5154

-

5158.(17) Hedden, R. C.; Saxena, H.; Cohen, C.

Macromolecules

2000

,

33

, 8676

-

8684.(18) Van Krevelen, D. W.

Properties of Polymers

; Elsevier: New York, 1990.(19) Swelling in terms of volume is calculated by

∆

V

)

S

3

.(20) In this paper, the number associated with the solvent, e.g., hexanes (8)indicates the rank of the solvent from Figure 1, in descending order of solvability in PDMS.

Table 1. Solubility Parameters, Swelling Ratios, andDipole Moments of Various Solvents Used in OrganicSynthesis

solvent

δ

a

S

b

µ

(D) ref

c

rank

d

perfluorotributylamine 5.6 1.00 0.0 10 32perfluorodecalin 6.6 1.00 0.0 10 33pentane 7.1 1.44 0.0 10 3poly(dimethylsiloxane) 7.3

∞

0.6

-

0.9 8, 14diisopropylamine 7.3 2.13 1.2 10 1hexanes 7.3 1.35 0.0 10 8

n

-heptane 7.4 1.34 0.0 10 10triethylamine 7.5 1.58 0.7 8,10 2ether 7.5 1.38 1.1 10 6cyclohexane 8.2 1.33 0.0 10 11trichloroethylene 9.2 1.34 0.9 10 9dimethoxyethane (DME) 8.8 1.32 1.6 10 12xylenes 8.9 1.41 0.3 10 4toluene 8.9 1.31 0.4 10 13ethyl acetate 9.0 1.18 1.8 8,10 19benzene 9.2 1.28 0.0 10 14chloroform 9.2 1.39 1.0 10 52-butanone 9.3 1.21 2.8 10 18tetrahydrofuran (THF) 9.3 1.38 1.7 10 7dimethyl carbonate 9.5 1.03 0.9 8,10 25chlorobenzene 9.5 1.22 1.7 10 15methylene chloride 9.9 1.22 1.6 10 16acetone 9.9 1.06 2.9 8,12 22dioxane 10.0 1.16 0.5 10 20pyridine 10.6 1.06 2.2 10 23

N

-methylpyrrolidone (NMP) 11.1 1.03 3.8 10 26

tert

-butyl alcohol 10.6 1.21 1.6 8,12 17acetonitrile 11.9 1.01 4.0 10 311-propanol 11.9 1.09 1.6 8,10 21phenol 12.0 1.01 1.2 8,12 29dimethylformamide (DMF) 12.1 1.02 3.8 8,10 27nitromethane 12.6 1.00 3.5 10 34ethyl alcohol 12.7 1.04 1.7 8,12 24dimethyl sulfoxide (DMSO) 13.0 1.00 4.0 10 35propylene carbonate 13.3 1.01 4.8 10 30methanol 14.5 1.02 1.7 8,12 28ethylene glycol 14.6 1.00 2.3 8,12 36glycerol 21.1 1.00 2.6 13,15 37water 23.4 1.00 1.9 8,12 38

a

δ

in units of cal

1/ 2

cm

-

3/ 2

.

b

S

denotes the swelling ratio that wasmeasured experimentally;

S

)

D

/

D

0

, where

D

is the length of PDMSin the solvent and

D

0

is the length ofthe dry PDMS.

c

References referto literature values of

δ

and

µ

.

d

Rank refers to the order of the solventin decreasing swelling ability (see Figure 1).

Analytical Chemistry, Vol. 75, No. 23, December 1, 2003

6545

substantially different from that of PDMS. This relation between

S

and

δ

, however, deviates in small but important ways. Forexample, acetone and methylene chloride have indistinguishablesolubility parameters (

δ

)

9.9 cal

1/ 2

cm

-

3/ 2

), but methylenechloride swells PDMS much more than does acetone. Thisobservation can be explained by the polarity of the solvent. Thesolubility parameter can be expressed by a sum of the dispersionforces, polar forces, and hydrogen-bonding forces within thematerial (Hansen’s total solubility parameter);

8

that is,

δ

2

)

δ

d2

+

δ

p2

+

δ

h2

. While two solvents may have a similar total solubilityparameter, the contributions that make up this value may bedifferent. Two solvents with the same value of

δ

but a differentproportioning of these values among

δ

d

,

δ

p

, and

δ

h

may showsubstantial differences in swelling on exposure to PDMS. Thepartitioning of

δ

that is most similar to that of PDMS will resultin the greatest swelling. Unfortunately, values of

δ

d

,

δ

p

, and

δ

h

are not readily available for PDMS or for many organic solvents.

21

In this paper, we consider the dipole moment of the solvent,

µ

(D) (representing the polar contributions), to help explain trendsin solubility, since

µ

is readily available for most materials (Table1). For example, in the case of acetone (

µ

)

2.88 D) andmethylene chloride (

µ

)

1.60 D), methylene chloride has smallerpolar contributions to

δ

than does acetone. PDMS has a

δ

madeup of primarily dispersion forces; PDMS also has low polarcontributions (

µ

)

∼

0.6

-

0.9 D),

22

so it is not surprising thatmethylene chloride is more soluble in PDMS than is acetone.We grouped the solvents in Figure 1 into four classifications,depending on their solubility effect on PDMS: solvents that havelow solubility (1.00

<

S

<

1.10), moderate solubility (1.10

<

S

<

1.22), high solubility (1.28

<

S

<

1.58), and extreme solubility(1.58

<

S

<

2.13). Some solvents in which solubility parameterswere not available are listed in Tables 2

23

and 3

24,25

and are alsoincluded in this analysis.

General Observations.

Low Solubility.

Low-solubility solventsgenerally have

δ

g

9.9 cal

1/ 2

cm

-

3/ 2

. These solvents range fromwater (38) to 1-propanol (21) and include most alcohols (1-propanol, ethanol, methanol, phenol, ethylene glycol, glycerol),nitriles (acetonitrile), disubstituted amides (NMP, DMF), andtetrasubstituted ureas (1,1,3,3-tetramethylurea), sulfoxides (DMSO,

(21) Literature values of

δ

d

,

δ

p

, and

δ

h

for a limited number of polymers andsolvents are available in: Du, Y.; Xue, Y.; Frisch, H. L.

Physical Properties of Polymers Handbook

; AIP Press: Woodbury, NY, 1996.(22) Diachun, N. A.; Marcus, A. H.; Hussey, D. M.; Fayer, M. D.

J. Am. Chem.Soc.

1910

,

32

; S

1994

,

116

, 1027

-

1032.(23) Chitra, R.; Smith, P. E.

J. Chem. Phys.

2001

,

115

, 5521

-

5530.(24) Simonyan, G. S.; Beileryan, N. M.; Pirumyan, E. G.; Roque, J.-P.; Boyer, B.

Kinet. Catal.

2001

,

42

, 474

-

478.(25) Graffeuil, M.; Labarre, J. F.; Leibovici, C.; Theophanides, T.

J. Chim. Phys.Physicochim. Biol.

1973

,

70

, 1295

-

1298.

Figure 1.

Relationship between swelling ratio (

S

) (shown as Log (

S

)) of PDMS in various solvents and the solubility parameter (

δ

) for thesesolvents. The solvents are numbered in order of decreasing swelling ability (e.g., “1” has the most swelling ability and “38” has the least swellingability). The dashed line indicates the solubility parameter of PDMS (

δ

)

7.3 cal

1/2

cm

-

3/2

). In general, a greater degree of swelling is observedwith solvents that have a value of

δ

similar to that of PDMS.

6546

Analytical Chemistry, Vol. 75, No. 23, December 1, 2003