Analysis of biomedical polymer surfaces: polyurethanes and plasma-deposited thin films

Clinical Maferials 13 (1993) 71-84

Analysis of Biomedical Polymer Surfaces: Polyurethanes and Plasma-Deposited Thin Films Buddy D. Ratner, * Bonnie J. Tyler & Ashutosh Chilkoti Department of Chemical Engineering and Center for Bioengineering, BF-10, University of Washington, Seattle, Washington 98195, USA

Abstract: The surface characterization of biomaterials is important for understanding the biological reactivity of surfaces and for monitoring surface reproducibility and contamination. Electron spectroscopy for chemical analysis (ESCA), secondary ion mass spectrometry (SIMS), contact-angle methods, vibrational spectroscopic methods, and scanning probe microscopies are briefly reviewed. Examples are presented using these methods to characterize RF plasma-deposited surfaces based upon acetone and oxygen for cell culture and BiomerTM surfaces.

INTRODUCTION

free of leachable components, a living system can interrogate the bulk of the material. ?? The surface of a material is inevitably different from the bulk of the material. tsurfaces will try to minimize their interfacial energy, leading to different surface atomic structures and chemistries. Traditional materials characterization methods examine the bulk of materials and not the surface. ?? Surfaces exhibit enhanced reactivities. This is a manifestation of the excess interfacial energy and the ready accessibility to external phases of surface atoms. Such enhanced reactivity is responsible for the catalytic properties of some surfaces. ?? There is a minute amount of material that comprises the surface zone. Typical surfaces contain in the order of lOI atoms/cm2 or 10P9 moles of material. Traditional analytical methods are often unable to analyze such small amounts of material. ?? Surfaces are difficult to study because they readily contaminate and often exhibit mobility, permitting the surface chemistry and structure to adjust in a ‘chameleon-like’ fashion to changing external environments.

Two classes of biomaterials that have received much attention arc polyurethanes and plasma-deposited thin films. The reasons for interest in these materials are ;summarized in Table 1. This article discusses some of the surface analysis techniques that can be applied to understand the nature of the surfaces of these two different types of material.

RATIONALE FOR SURFACE CHARACTERIZATION

Understanding the nature of the surface of a biomaterial is essential both for understanding the interactilons between materials and living systems, and for fabricating biomaterials and biomedical devices. Surface analysis methods provide the means for gaining that understanding. The rationale for using surface analysis techniques in biomaterialls science can be summarized as follows: o The surface of a material (the outermost few atomic layers) is the only portion of the material that can interact with proteins and cells, i.e. there is no way that, for a material * To

whom correspondence

This rationale has been elaborated number of review articles.lP6

should be addressed. 71

Clinical Materials 0267-6605/93/$6.00

0

1993 Elsevier Science Publishers

Ltd, England

upon

in a

Buddy

72

Table 1. Advantages Plasma-Deposited

D. Ratner,

of plasma-deposited

Bonnie

Ashutosh

films and polyurethanes

~~~~kot~ for biomedical

applications

Films

Dry processing (no solvents or emissions) Rapid (often only seconds are needed) Pin-hole free coatings Conformal coatings (fabrics, complex parts) Can be manufactured on continuous basis Tenacious adhesion to the substrate (minimized delamination) Many possible chemistries (most organic) Many possible substrates (metals, glasses, carbons, polymers) Monomer costs are negligible Good tissue biocompatibility Sterile product comes from the reactor Much precedent (widely used in the microelectronics industry)

SURFACE CHARACTERIZATION METHODS Before 1960, few methods were available for studying surfaces. From 1960 to the present, a large number of methods have been developed with the special surface sensitivity needed to isolate the analysis to just the surface zone of the material. It is impractical, and often technically impossible, to apply all available methods to the analysis of a surface. Still, the more methods that are brought to bear on the problem, the more ‘pieces of the puzzle’ that will be available for determining the surface structure. Information from multiple surface analysis methods is often corroborative and synergistic in developing an understanding of surface structure. The following sections provide a brief introduction to a few of the techniques particularly useful for characterizing biomaterial surfaces. Table 2. The ESCA experiment: In the outermost

J. Tyler,

JO0 A”of a surface, ESCA

0

Excellent strength and toughness Good tissue ~~~c~~~~at~bility Unparalleled long-term resistance to mechanical failure under flexure Some reports of good $100 Some reports of long-term in-vivo stability Many manufacturing options (sheet, tube, foam, fiber, etc.) Many synthetic chemistry options to modify the bulk and surface structure A wide range of mechanical properties can be prepared Much precedent as a biomaterial

Electron spectroscopy for chemical ana

-ray photoelectron upon the emission

ability to ~~~et~at~ matter, emitted near the surface (in

Information

derived and a

can provide.

o Identification

of all elements (except I-I and He) present at concentrations > 0~1 at.% determination of the approximate elemental surface composition (?K10%) ?? Information about the molecular environment (oxidation state, bonding atoms, etc.) ?? Information about aromatic or unsaturated structures from shake-up (T* + T) transitions ?? Identification of organic groups by using derivatization reactions ?? Nondestructive elemental depth profiles 100 A into the sample and surface heterogeneity assessment by using (I ) angular-dependent ESCA studies and (2) photoelectrons with differing escape depths ?? Destructive elemental depth profiles several thousand angstroms into the sample by using argon etching (for inorganics) ?? Lateral variations in surface composition (8-l 50 /-lm spatial resolution, depending upon the instrument) ?? ‘Fingerprinting’ of materials by using valence band spectra and identification of bonding orbitals ?? Semiquantitative

Advantages

of ESCA:

o Special sample preparation is generally not needed on hydrated (frozen) surfaces can be performed o Minimal sample damage ?? Well-developed theory assists interpretation o Refined instrumentation simplifies sample handling and data collection ?? Studies

Analysis of biomedical polymer surfaces

73

Computer: Instrument control EZZZS ) and data analysis

(I@

torr)

I

vacuum

I

1

(lO‘lOtorr)

]

I I

Fig. 1. A xhematic diagram showing the components of a typical monochromatized ESCA instrument. The specimen within the analysis chamber illustrates that ESCA is a surface-sensitive method. Although the X-ray beam can penetrate far into a specimen, electrons emitted deep within the specimen (ID, E, F, G) will lose their energy in inelastic collisions and never emerge from the surface. Only those electrons emitted near the surface that lose no energy (A, B) will contribute to the ESCA signal used analytically. Electrons that lose some energy, but still have sufficient energy to emerge from the surface (C), contribute to the ‘background signal.

ods can enhance ESCA and add to its information content. Some of these methods include angulardependent ESCA,‘5P17 cold-stage studies,““’ imaging .the spatial distribution of surface chemistry with ESCA,20-23 and chemical derivatization.24-27 The application of these methods to biomaterials is elabor,ated upon later in this chapter. Secondary ion mass spectrometry

The seciondary ion mass spectrometric (SIMS) method bombards a surface with a focused beam of ions or atoms. The energy from the incident beam (typically 3-5 keV) is transferred to the surface zone of the material and can lead to the ejection of iatoms, ions, or complex fragments from the surface. The mass-to-charge (m/z) ratio of positive and negative species is then measured to provide the SIMS spectrum. This process is illustrated in Fig. 2. Many general review articles on SIMS are available.28-32 If the bombarding flux is sufliciently low, relatively little damage will be done to the surface and the fragments emitted will be characteristic: of the surface molecular structure. Low flux SIMS is often referred to as static SIMS.29133 If the flux is high, the incident beam will etch the

surface. This dynamic SIMS method provides a depth profile (a plot of relative concentration WYSW depth) of elements present in the surface zone. Table 3 lists information obtained from the SIMS experiment and discusses some of its advantages. Specialized methods that can enhance the SIMS information content include chemical derivatization,34 isotope substitution,35 tandem SIMS,36 high spatial resolution imaging,3c’>37’38and new mass detection methodologies suich as time-offlight mass analysis.39 Some of these SIMS methods will be further discussed below. Contact-angle

methods

The measurement of the angle with >whicha drop of liquid contacts a surface represents one of the earliest methods used to investigate surface structure, but one that still yields much useful information. Contact-angle methods provide information primarily on surface energetics. However, acidbase contact-angle methods yield clues to surface chemistry.40 There are many other specialized contact-angle methods that can enhance the usefulness of contact angles for characterizing surfaces. For example, underwater contact-angle methods (e.g.

74

sample Vacuum chamber

Fig. 2. Schematic

diagram

octane drop in water or air bubble

in water) study the relevant hydrated interface. WiIhelmy plate methods increase the reproducibility and accuracy of contact-angle methods. Advancing and receding

Fig. 3. Schematic

diagram

of a static SIMS experiment.

information on surface Obiany reviews have been echniques for characherizing the s~r~c~~ of solids.41-43

of a surface being imaged by ST

Analysis of biomedical polymer surfaces Table 3. Information

derived from static and dynamic

SIMS experiments

Vibrational spectroscopy, in particular infrared spectroscopy (IR), is a well-established method to obtain information about molecular structure. By measuring the frequency of IR radiation needed to excite vibrations in molecular bonds, important details of the structure and molecular interactions

Principle

Method Contact

angles

Liquid wetting of surfaces is used to estimate the energy of surfaces

J J J

J J

can be explored.44 The attenuated total reflectance (ATR) sampling mode first permitted IR analysis in the surface region of a solid.45-“i8Methods such as diffuse reflectance IR49 and external reflection IR50-53 further enhance the ability of vibrational spectroscopy to study surface problems. Other vibrational spectroscopic methods applicable to surface problems include surface-enhanced Raman

Vibrational spectroscopy methods

and concerns

Dynamic SIMS J J

Static SIMS J J J J J

Identification of hydrogen Identification of other elements (often must be inferred from the data) Suggests molecular structures (inferred from the data) Observation of extremely high mass fragments (proteins, polymers) Detection of extremely low concentrations Depth profiling up to 1 pm into the sample Observation of the outermost l-2 atomic layers High spatial resolution (features as small as N 500 A) Semiquantitative analysis (for limited sets of specimens) Useful for polymers Useful for inorganics (metals, ceramics, etc.) Useful For powders, films, fibers, etc.

Table 4. Capabilities

75

with common Depth analyzed 3-20 A

to characterize

Spatial resolution lmm

biomaterial Analytical

surfaces

sensitivity

Concerns

Low or high, depending upon the chemistry

Liquid swells, penetrates or extracts sample

lO-150pm

0.1 at.%

X-ray damage; interpretation can be complex

ESCA

X-rays cause the emission of electrons of characteristic energy

lo-250

Auger electron spectroscopy

A focused electron beam causes the emission of auger electrons

50-lOO A

100 A

0.1 at.%

Severe sample damage; quantitation

SIMS

Ion bombardment leads to the emission of surface secondary ions

10A-l pm*

SO0 A

Very high

Sample damage; quantitation

FTIR-ATR

IR radiation is absorbed in exciting molecular vibrations

1Opm

1 mole %

Water subtraction; interpretation

STM

Measurement of the quantum tunneling current between a metal tip and a conductive surface

58,

1A

Single atoms

Sample damage; artifacts

SEM

Secondary electron emission caused by a focused electron beam is measured and spatially imaged

5A

40 A typically

High, but not quantitative

Sample damage; preparation artifacts

* Static SIMS = 10 A, dynamic

SIMS to 1 pm.

ll5prn

A

methods

76

Fig. 4. STM image of a fibrinogen (Data acquired spectroscopy54

spectroscopy

molecule by Dr K.

and inelastic (IETS).5595”

on a gold surface.

electron

tunnelin

ve materials and sur-. faces sf biological a aterial interest.67-7d any other scanning probe microscopes have been developed An e~eet~Qe~e~~e~~ se~~~~~~ probe a~~~~~~~~~~ may permit ion ~ist~~b~~~~r~s across a surface to be mapped.7’mm77

Scanning probe microscopies In the last ten years we have seen the development of a family of methods t t permit surface chemistry and morphology to e probed with unprecedented spatial resolution.57-60 The scanning tunneling microscope @TM) observes a surface by moving a metal tip terminating in a single atom within quantum tunneling distance (S-10 A> of a

Fig. 5. Schematic

diagram

is is a brief ~~~r~d~c~i~~ to a few oi’ the many ethods available to characterize surfaces. thea new methods, for e

these newer me

of an RF plasma reactor.

Analysis of biomedical polymer surfaces %O (ESCA)

25

T-

o

>

II

4

%

IO

Oxygen

20

30

40

50

60

70

-

H + (CF3 - CO),0

-

OOH

-

&

0

+ NH,NH,

77

+ CF,-CH,OH

>=N..NH2

O-CO-CF3

%W

+ (CH3)3C=NC=NC(CH3)3

Fig. 7. Three

derivatization plasma-deposited

+ l-20

+ CF3 - COOH

OzC’VF, 8

O II + (CH3)3CNH-C-NHC(CH3)3

reactions used in the study acetone-oxygen films.

of

Gas in Reactor Feed

Fig. 6. ESCA-measured percent oxygen for the acetonee02 plasma-deposited film veY,sUSpercent flowrate of O2 gas in the reactor feed; filled squares, set I; open squares, set II. (Reprinted1with permission from Ref. 24. Copyright 1991, American Chemical Society.)

research in the near future. Although surface analysis methods provide much insight into the surface structure of biomaterials, each method requires an understanding of the physics involved, analytical quantitation, and limitations. Table 4 summarizes and cornpares the advantages and concerns of many methods available for characterizing surfaces.

TWO E:XAMPLES ILLUSTRATING THE USE OF SURFACE CHARACTERIZATION METHODS FOR BIOMATERIAL PROBLEMS Cell culture surfaces prepared by plasma deposition The deplosition of thin films (20-2OOOA) in an RF plasma environment of low-pressure ionized gas has found wide application in biomaterials science.81s2 A simplified diagram of an RF plasma reactor is presented in Fig. 5. The thin films that form under appropriate reaction conditions are highly adherent to the substrate, are sterile, can be applied to a wide range of substrates, and offer much flexibility for adjusting the film chemistry. Such RIF plasma films prepared by depositions from volatile carbon-oxygen organic compounds (e.g. acetone, methanol, glutaraldehyde, formic Table 5. Concerns

acid) onto solid supports have shown promise for culturing cells.83-86 However, the chemical nature of these films is complex, an the relationship between the composition of the ms and their ability to support cell growth is unclear. To explore this relationship, surface analytical methods were used to clarify aspects of film composition. It was noted that RF plasma acetone depositions will not support bovine aortic endothelial cell (BAEC) growth. However, if oxygen was blended into the plasma reactor during the acetone deposition, cell growth increased with increasing surface oxygen content.84 The oxygen content of the films, as measured by ESCA, increased with increasing fraction of oxygen in the feed gas flow (Fig. 6). Since many common polymers with. surface oxygen contents equivalent to those formed by the acetone-oxygen RF plasma (e.g. poly(ethylene terephthalate), poly(2-hydroxyethyl methacrylate), poly(viny1 alcohol), poly(viny1 methyl ether)) will not support cell growth, the oxygen content alone cannot explain what makes these acetone-oxygen plasma-deposited films good cell culture substrates. We hypothesized that the nature of the functional groups present was more mportant than the total oxygen content. ESCA as only a limited ability to discriminate different carbon-oxygen functional groups on surfaces. Therefore, enhancements of the ESCA method were needed to expand its analytical utility. An enhancement of the ESCA technique that provided new insight into functional groups prein derivatization

studies

a Is the reaction stoicbiometric? . What are the kinetics of the reaction (i.e. is it complete)? ?? The tag molecule should contain an atom (or atoms) that are absent from the starting ?? The derivative formed should be stable under vacuum. . The derivative formed should be stable with time. . Surface rearrangement can alter the initial surface or ‘hide’ the derivatizing group. a The derivatizing reagent may extract, and thereby alter, the surface under analysis. --

surface and have a high ESCA sensitivity.

Buddy D. Ratner, Bonnie J. Tyler, A~~~t~s~ ~~~~~o~i

78 Positive

Ion SIMS Spectra Acetone-40% 02 PDF

41 W45+ 2000

GHO+

1200

1000

800

600

400

J.--b+0

20

200

60

80

4’e

il

2

4

4 0

l__-

6500

Poly(methyl lsopropen

4875

3250

1625

0

Figure 8. Positive ion (a))(c) and negative ion (d)-(f) SIMS spectra of an acetoneeN.% Q2 plasma-deposited film ( methyl ketone) (PVMK), and poly(methy1 isopropenyl ketone) (PMIPrK). I n comparing the positive ion spectra ences are seen. However, in the negative ion spectra, while the acetone PDF and PMIPrK spectra resemble each spectrum contains a prominent m/z 57-peak. This suggests the structures in acetone PDF may be more similar to

sent at the surface of RF plasma-deposited films was chemical derivatization. By reacting groups at the surface with chemical reactants that incorporated elements not previously present in the film, elemental analysis of the derivatized surface pro-

;i

Analysis

of biomedical polymer

Table 6. Similarities between an acetone-oxygen

surfaces

plasma-deposited

79

film and conventional

polymers

Oxygen-containing units

Polymer

Present a

PVA

-OH

PVME

-0-CH,

PVEE

-0-C2H5

PVlsBuE

-0-CH,CH(CH&

-i?--H3 0

PVMK

PVEK

-g-

H

C2H5

0

PMlsPrK

-E-

CH3

CH3

Y

0

PVAc

H

-

0-g-CH,

Y

0

PVPr

H

-

O-C-CpH5

N

Li

PVBu

N

H -

o-r

C3H7 0

a Y, N and P indicate yes, no and possibly.

acetone--oxygen plasma-deposited films.24 These studies suggested that carbonyl groups might be important in cell growth.86 SIMS studies were also performed to gain further insights into the nature of these RF plasma-deposited acetone-oxygen thin films. SIMS data can be used in three ways to assist in the understanding of surface structure. First, spectra of materials can be used as ‘fingerprints’; comparison with spectral libraries helps identify materials and the similarities between materials. Second, the chemistry of specific peaks of interest can be elucidated. Third, the relationship between a specific SIMS fragment and the surface chemistry that produced it can be establishled. The first and second of these methods

of using SIMS data are presented here. Relationships between specific SIMS fragments and surface chemistry have been established in another study.87 Comparisons between SIMS spectra from plasma-deposited acetone-oxygen films and SIMS spectra of well-defined conventional polymers were made to assess the probability that specific molecular functionalities were present in the plasma films.35 An example of this pattlern recognition process is illustrated in Fig. 8. Based upon this method, some of the similarities between these plasma-deposited films and conventional polymers are suggested in Table 6. This simp1.e pattern recognition process can be greatly enhanced by multivariate statistical methods such as partial least-squares

80

CHsCC 43.01:

Fig. 9. The TOF detection technique provides enhanced mass analysis as evidenced by the resolution of an m/z = 43 peak in a SIMS spectrum into two components.

(PLS) analysis to model t e relationships between all the SIMS peaks and the hydrocarbon content or carbonoxygen functionality of the conventional polymer set. The model constructed can then be applied to the SIMS spectra of the plasma-deposited films.88 The identification of the chemical structures associated with specific peaks can be assisted in two ways: by introducing stable isotopes into the plasma reactor, and by using SIMS with enhanced mass resolution (e.g. time of flight (TOF) detection). The mass-to-charge (m/z) peak at m/z = 43 seen in the SIMS spectrum of the acetone plasma deposition serves as a od example. This peak might be associated wi a CHsCO+ ion or a C3H7+ ion, both of which have ypz/z = 43, based upon the 1 m/z resolution typically observed with a quadrupole mass detector (the most common type of mass detection used with SIMS). By using acetone synthesized with t3C instead of the naturally abundant 12C for the plasma deposition, it was found that the oxygen-containing ion predominates at m/z = 43.35 This analysis can be performed more simply by using the high-resolution mass analysis of TOF SIMS. Figure 9 shows how, by using TOF detection, the m/z = 43 peak can be readily resolved into its two components, based upon more precisely calculated molecular weights for the fragments.89

290

295

285

Fig. 10. ESGA C Is s ectra of BiomerTY’ lots BSP and

ity because

of its

We examines two lot BSP067 and BSUAOOl ~91

compared in Fig. that there are large

Analysis

of biomedical polymer

tion, the chemical functionalities indicated by peak shapes and binding energy positions in the oxygen and nitrogen regions are characteristic of polyurethanes. Lot BSUA , on the other hand, has a C 1s spectrum showing too high a fraction of hydrocarbon-type carbons and an acid or ester functionality, rather ,than a carbamate polyurethane bond. The N 1s region suggests predominantly amine groups, rather than the expected carbamate and urea functionalities. Angular-dependent ESCA studies on films of these two polymers reveal that for lot BSP, polyether content increases and nitrogen (hard segment) content decreases as the outermost surface is approached. This has been observed before with BiomerTM and other poly(ethler urethane) segmented block copolymers.” Lot BSIJA surfaces, in contrast, show increasing nitrogen as the outermost surface is approached. Static SIMS analysis of the two BiomerTM surfaces provided more information. Lot BSP generated positive ion peaks characteristic of poly(tet:ramethylene oxide) (PTMO) (m/z = 145, 127, 10 1, 85, and 71), methylene diphenyl diisocynate (MDI)l (m/z = 180, 165, 150, 132, and 106), and, most likely, an antioxidant (m/z = 177 and 161). There was relatively little information (few characteristic peaks) in the negative ion spectrum of this lot. For lot BSUA, the positive ion SIMS spectrum did not show peaks characteristic of PTMO or MDI. In sharp contrast to BSP, the BSUA negative ion SIMS spectrum was rich in molecular information. Many peaks characteristic of methacrylates were found (m/z = 85, 97, 109, 125, 139, and 155). Other positive and negative ion peaks present at this surface can be assigned as fragments originating from poly(diisopropy1 aminoethyl methacrylate) (DPA-EMA), an antioxidant added to polymers. These: data strongly suggest that BiomerTM lot BSUA is dominated at its surface by DPA-EMA. Lot BSP has a surface that is characteristic of poly(ether urethanes). The importance of these surface differences for bioreaction to the two lots has not yet been established. However, large differences in the biostability of the two lots to enzymatic and oxidative degradation were noted.94’95

CONCLUSIONS

Some of the contemporary methods available to measure the chemistry and structure of surfaces are described ‘briefly in this review. Two examples

surfaces

81

were presented illustrating the use of some of the many methods available to provide insight into the nature of complex surfaces. Such information will be essential in ensuring the re:producibility of materials from experiment to experiment and day to day, in manufacturing quality control, and in developing insights into the relationships between surface structure and biological reactivity. The importance of surface chemistry for biological reaction has been addressed in other publications.’

REFERENCES 1. Ratner, B. D., Surface structure and properties. In Concise Encyclopedia o-f Medical and Dental Materials, ed. D.F. Williams. Pergamon Press, Oxford, UK, 1990, pp. 337-46. 2. Ratner, B. D., Chilkoti, A. & Castner, D. G., Contemporary methods for characterizing complex biomaterial surfaces. Clin. Mater. 11 (1992) 25-36. 3. Ratner, B. D., Castner, D. G., Horbett, T. A., Lenk, T. J., Lewis, K. B. & Rapoza R. J., Biomolecules and surfaces. J. Vat. Sci. Technol. A, 8 (1990) 2306-17. 4. Ratner, B. D., ESCA for the study ofbiomaterial surfaces. In. Polymers in Medicine ZZ,ed. E. Chiellini, P. Giusti, C. Migliaresi & L. Nicolais. Plenum Press, New York, 1986, pp. 13-28. 5. Ratner, B. D., Johnson, A. B. & Lenk, T. J., Biomaterial surfaces, J. Biomed. Mater. Rex Appl. Biomat., 21 (1987) 59990. 6. Ratner, B. D., Surface structure of polymers for biomedical applications. Makromol. Chem., Macromol. Symp., 19 (1988) 163378. 7. Andrade, J. D., X-ray photoelectron spectroscopy (XPS). In Surface and Interfacial Aspects of Biomedical Polymers, Vol. 1: Surface Chemistry and Physics. ed. J. D. Andrade. Plenum Press, New York, 1985, pp. 105-95. 8. Miller, D. R. & Peppas, N. A., The use of X-ray photoelectron spectroscopy for the analysis of the surface of biomaterials. J. Macromol. Sci.-Rev. Macromol. Chem. Phys., C26 (1986) 33366. 9. Carlson, T. A., Photoelectron and Auger Spectroscopy. Plenum Press, New York, 1975. 10.Briggs, D. & Seah, M. P., Practical Surface Analysis. John Wiley & Sons, Chichester, UK, 1983. 11. Siegbahn, K., Electron spectroscopy for solids, surfaces, liquids and free molecules. In MolecuLzr Spectroscopy, ed. A.R.West. Heyden and Sons Ltd, London, UK, 1977, pp. 227-312. 12. Ratner, B. D. & McElroy, B. J., Electron spectroscopy for chemical analysis: Applications in the .biomedical sciences. In Spectroscopy in the Biomedical Sciences, ed. R. M. Gendreau. CRC Press, Boca Raton, FL, 1986, pp. 107-40. 13. Dilks, A., X-ray photoelectron spectroscopy for the investigation of polymeric materials. In Et’ectron Spectroscopy: Theory, Techniques, and Applications, Vol. 4, ed. A. D. Baker & C. R. Brundle. Academic Press, London, UK, 1981, pp. 2777359. 14. Clark, D. T., Some experimental and theoretical aspects of structure, bonding and reactivity of organic and polymeric systems as revealed by ESCA. Physica Scripta, 16 (1977) 307-28. 15. Fadley, C. S., Solid state and surface-analysis by means of angular-dependent X-ray photoelectron spectroscopy. Frog. Sol. State Chem., 11 (1976) 2655343.

16. Tyler, B. J., Castner, D. 6. & Ratner, B. D., Regularization: A stable and accurate method for generating depth profiles from angle dependent XPS data. Surf. Interface Anal., 14 (1989) 443350. 17. Ratner, B. D. & Paynter, R. W., Polyurethane surfaces: The importance of molecular weight distribution, bulk chemistry and casting conditions. In Polyurethanes in Biomedical Engineering, Progress in Biomedical Engineering, Vol. 1, ed. H. Planck, G. Egbers & 1. Syre. Elsevier, Amsterdam, The Netherlands, 1984, pp. 41-68. 18. Ratner, B. D., Weathersby, P. K., Hoffman, A. S., Kelly, M. A. & Scharpen, L. H., Radiation-grafted hydrogels for biomaterial applications as studied by the ESCA technique. J. Appl. Polym. Sci., 22 (1978) 643364. 19. Lewis, K. B., Ratner, B. D., Klumb, L. A. & Ertel, S. I. Surface restructuring of biomedical polymers. Trans. Sot. Biomater., 14 (1991) 176. 20. Seah, M. P. & Smith G. C., Concept of an imaging XPS system. Sur$ Interface Anal., 11 (1988) 69-79. 21. Hoffmann, D. P., Proctor, A. & Hercules, D. M., Spatially resolved ESCA using Hadamard masks. Appl. Spectrosc. 43 (1989) 899-908. 22. Ebel, H., Ebel, M. F., Mantler, M. Barnegg-Golwig, G., Svagera, R. & Gurker, N., Imaging XPS with a hemispherical analyzer and multichannel plate detection. Surf. Sci., 231 (1990) 233-9. 23. Briggs, D., New developments in polymer surface anlysis. Polymer, 25 (1985) 1379-91. 24. Chilkoti, A., Ratner, B. D. & Briggs, D., Plasma-deposited polymeric films prepared from carbonyl-containing volatile precursors: XPS chemical derivatization and static SIMS surface characterization. Chem. Mater., 3 (1991) 51-61. 25. Chilkoti, A. & Ratner, B. D., An X-ray photoelectron spectroscopic investigation of the selectivity of hydroxyl derivatization reactions. Surf. Interface Anal., 17 (1991) 567774. 26. Batich, C. D., Chemical derivatization and surface analysis. Appl. Surf. Sci., 32 (1988) 57-73. 27. Chilkoti, A. & Ratner, B. D., Chemical derivatization methods for enhancing the analytical capabilities of X-ray photoelectron spectroscopy and static secondary ion mass of Advanced spectrometry. In Surface Characterization Polymers, ed. L. Sabbatini. VCH Publishers, Weinheim, Germany, 1992. 28. Castner, D. G. & Ratner, B. D., Static secondary ion mass spectroscopy: A new technique for the characterization of biomedical polymer surfaces. In Surface Characterization of Biomaterials, ed. B. D. Ratner. Elsevier Press, Amsterdam, The Netherlands, 1988, pp. 65581. 29. Vickerman, J. C., Brown, A. & Reed, N. M., Secondary Ion Mass Spectrometry. Principles and Applications. Clarendon Press, Oxford, UK, 1989. 30. Pignataro, S. & Licciardello, A., Static imaging and dynamic SIMS in the study of surfaces and interfaces of materials. Gazz. Chim. Ztal., 120 (1990) 351-63. 31. Katz, W. & Newman, J. G., Fundamentals of secondary ion mass spectrometry. MRS Bulletin, XII (1987) 40-6. 32. Niehuis, E., Secondary ion mass spectrometry of organic materials. In Proc. Sixth Znt. Conf~ on Secondary Ion Mass Spectrometry (SIMS VI), Vol. 1, ed. A. Benninghoven, A. M. Huber & H. W. Werner. John Wiley & Sons, Chichester, UK, 1988, pp. 591-8. 33. Davies, M. C. & Lynn, R. A. P., Static secondary ion mass spectrometry of polymeric biomaterials. CRC Crit. Rev. Biocompat., 5 (1990) 297--341. 34. Chilkoti, A. Castner, D. G., Ratner, B. D. & Briggs, D., Surface characterization of a poly(styrene/p-hydroxystyrene) copolymer series using XPS, static SIMS, and chemi-

cal derivatizat~~~ techniques. 9. Vat. Sci. Technoi. A, (1990) 2274482. 35. Chilkoti, A., Ratner, riggs, D., A static secondary ion mass spectromet gation of the surface structure of organic plasma-deposited films prepared from stable isotope-labeled precursors. Part I. Carbonyl precursors. Anal. Chem., 63 (1991) 1612.20. 36. Leggett, G. J., Vickerman, J. C. B Briggs, D., Applications pole mass spectrometry in SIMS. %d$ (1990) 3-8. 37. Briggs, D., Rcce advances in secondary ion mass spectrametry (SIMS) for polymer surface analysis. Br. Bolym. ,B.,

39. 40.

41.

42.

43.

45. 46. 47.

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