Time of Flight SIMS and MALDI Studies of the Surface Chemistry of PolySiloxanes and Biodegradable Polyesters: Quantitation

Transcription

1 Time of Flight SIMS and MALDI Studies of the Surface Chemistry of PolySiloxanes and Biodegradable Polyesters: Quantitation Joseph A. Gardella, Jr. Professor of Chemistry & Associate Dean College of Arts and Sciences SUNY Buffalo Acknowledgements Co-Workers Collaborators Dr. Maurizio Toselli (Univ. Bologna) Dr. Won Ki Lee (Pusan Univ.) Dr. Ilario Losito (Univ. Bari) Dr. Adam M. Hawkridge (Mayo Clinic) Dr. JiaXing Chen (Dow, Texas) Prof. Wesley Hicks, Jr. (Roswell Park) Dr. Joo Woon Lee (Univ of Texas, Bioengineering) Dr. Terrence G. Vargo (Integument) Prof. Patrick Aebischer, Univ Lausanne) Dr. Evan Bekos (Evans East) Prof. Robert Valentini (Brown Univ) Dr. Denise Carney (D Youville College) Dr. John Ranieri (Carbomed) Dr. Limin Sun (Univ. of Toronto) Dr. Timothy Koloski (Integument Tech) Dr. Daniel Ammon (Bausch&Lomb) Dr. Wen Yan Yan (Bausch&Lomb) Dr. Paul L. Valint, Jr. (Bausch&Lomb) Dr. George L. Grobe III (DePuy, Inc.) Dr. Richard Nowak 1

2 Acknowledgements National Science Foundation Chemistry Division ffice of Naval Research Chemistry Division - Molecular Interactions at Marine Interfaces (MIMI) NIH (Brown University) Bausch & Lomb Healthcare International New York State Science and Technology Foundation Quantitative ToF-SIMS and MALDI of Polymer Surfaces utline Quantifying Amounts PDMS Impurities in Contact Lens (SIMS) Depth Profiles of Polymer Blends (SIMS) Quantifying Polymer Mw PDMS MW mixtures in PMMA (MALDI) Kinetics of PDMS polymerization (MALDI/SIMS) Quantifying Kinetics of Reactions (SIMS) Degradation Kinetics of Biodegradable Materials Simultaneous Drug Release/Degradation Kinetics 2

3 Quantitative Analysis Precision Accuracy LQ, LD, etc. Sensitivity In-Depth Analysis Sampling Depth Low Temperature Angle Dependent XPS Research Themes Polymer Surface Chemistry Low Surface Energy (Si, F) Structure/Property Surface Structure Reactivity Link to Applications Microelectronics Tissue Engineering Coatings Anti Corrosion Minimal Fouling Time-of-Flight Secondary Ion Mass Spectrometry Provides information at the topmost few atomic layers Very high sensitivity to detect species with very low concentration Imaging capabilities with spatial resolution ca. 2µm (Cs + primary ion gun) Sample surface chemistry preserved under static condition 3

4 Bioadhesion and Bioabhesion to Polymers Low Surface Energy Materials: Minimal Biological Adhesion Fluoropolymers Siloxanes (PDMS Silicone ) Polyethylene xide/glycol (PE/PEG) Perfluoropolyethers Bio-Active Polymer Surfaces: Rearrangement/Segregation Degradation Biological Recognition/Specificity at Surfaces Quantitative ToF-SIMS and MALDI of Polymer Surfaces utline Quantifying Amounts PDMS Impurities in Contact Lens (SIMS) Depth Profiles of Polymer Blends (SIMS) Quantifying Polymer Mw PDMS MW mixtures in PMMA (MALDI) Kinetics of PDMS polymerization (MALDI/SIMS) Quantifying Kinetics of Reactions (SIMS) Degradation Kinetics of Biodegradable Materials Simultaneous Drug Release/Degradation Kinetics 4

5 Analysis of Commercial Contact Lens Systems by XPS and SIMS H 2 C C H 2 C C H 2 C C C= n =C m C= CH 2 CH 2 H CH 2 CH 2 HEMA EGDMA -69Da (C 4H 5 + ) -73Da ( ) 3 Si Da (C 6 H 9 2 ) + Counts -127Da (H 3 )(H 2 ) Da (H 3 )(H 2 ) Da [( ) 5 Si 2 ] + Counts m/z 5

6 Standard Additions Da/69Da Peak Ratio10 y = 0.25x+1.5 x-intercept = -6.0 ± 2.4 r 2 = Da/113Da Peak Ratio ng of PDMS Added to SeeQuence Lens y = 0.25x+0.6 x-intercept = -2.4 ± 1.0 r 2 = ng of PDMS Added to SeeQuence Lens PDMS Quantification Area of a PDMS molecule 50Å 2 = 5x10-15 cm 2 Area of SeeQuence lens segment = cm 2 2.4ng PDMS = 6.23x10-12 mol PDMS 6.23x10-12 mol PDMS = 3.75x10 12 molecules of PDMS 3.75x10 12 * 5x10-15 cm 2 = 0.02 cm 2 Area occupied by PDMS (0.02 cm 2 / cm 2 )*100 = 6.6% ± 2.8% monolayer coverage of PDMS 6

7 Quantitative ToF-SIMS and MALDI of Polymer Surfaces utline Quantifying Amounts PDMS Impurities in Contact Lens (SIMS) Depth Profiles of Polymer Blends (SIMS) Quantifying Polymer Mw PDMS MW mixtures in PMMA (MALDI) Kinetics of PDMS polymerization (MALDI/SIMS) Quantifying Kinetics of Reactions (SIMS) Degradation Kinetics of Biodegradable Materials Simultaneous Drug Release/Degradation Kinetics PLLA/Pluronic Blend model PLLA: crystalline region + amorphous region Blend: a third region in the hydrated film Water-filled pores (F108/PLLA) A liquid-crystalline phase (L101/PLLA) P104/PLLA blends: between these two extremes Presence of Pluronic in PLLA Changes of the structure of the PLLA matrix -> Changes of the degradation rate-> Changes of the drug-release rate from the matrix 7

8 Biocompatibility Pluronic surfactants Clinical uses FDA approved marketed drugs (Geriplex FS Liquid) PLLA FDA approved Biocompatible degradation product: lactic acid Uses in medical area Justifications Importance of Surface Study Surface Segregation: Due to the Difference of Surface Energies in components Surface Chemistry Affects: Degradation Kinetics -> Drug Release Rates Drug activities Cell Adhesion to the Implanted Devices Interlayer Adhesion Mechanical Properties Quantification of the surface concentration 8

9 Samples Prepared Name PLLA PLLA% 100% 99% 98% 97% 96% Name PLLA% 95% 90% 85% 80% 75% Name P104 PLLA% 70% 65% 60% 55% 50% 0% Blend XPS Results 1-5wt% P104 blends: the sharp slope; the 10-50wt% blends: less sharp slope A relatively homogenous region from 73Å to 103Å No points on the unit line P104 Surface Weight Percentage 90% 80% 70% 60% 50% 40% 30% 20% 10% 15deg 30deg 45deg 90deg Unit 0% 0% 10% 20% 30% 40% 50% P104 Bulk Weight Percentage 9

10 Normalized Intensity (log scale) 0.01 TF-SIMS Depth Profiling Da, Si 59 Da, from P Da, from PLLA x x x x x10 15 Ion Dose (Ions/cm 2 )) 75% PLLA in bulk Sample thickness: 6200 Å 59 Dalton: (P+H) + and (E+ ) + fragments from P Dalton: (2LA-) + fragment from PLLA The Intensity: normalized to the total ion intensity TF-SIMS Depth Profiling Normalized Intensity (log scale) % PLLA Normalized Intensity (log scale) E-3 1E-4 95% PLLA x x x x x x x x x x10 15 Ion Dose (Ions/cm 2 )) 28 Da, Si Ion Dose (ions/cm 2 ) 59 Da, from P Da, from PLLA 10

11 TF-SIMS Depth Profiling A depletion zone 75% PLLA blends: Deeper (~730 Å, calculated) 5% PLLA blends: Shallower (~ 267 Å, calculated) No interaction between the air surface and the interface A stable mixture between the air surface and the interface To compare to the XPS data Limit to the topmost 100 Å XPS results: need to be deconvoluted Identical Trends Quantitative ToF-SIMS and MALDI of Polymer Surfaces utline Quantifying Amounts PDMS Impurities in Contact Lens (SIMS) Depth Profiles of Polymer Blends (SIMS) Quantifying Polymer Mw PDMS MW mixtures in PMMA (MALDI) Kinetics of PDMS polymerization (MALDI/SIMS) Quantifying Kinetics of Reactions (SIMS) Degradation Kinetics of Biodegradable Materials Simultaneous Drug Release/Degradation Kinetics 11

12 Quantification of Mixtures of PDMS ligomer Distributions in PMMA matrix Mixtures of Low PDI (< 1.1) ligomer distributions PMMA Matrix Quantification using integration of all oligomer ions Summation to get integrated intensity Plot versus Monomer moles PDMS ligomers Mn=2200 Mn=6140 Counts ASMS/NIST Workshop on Mass (m/z) 12

13 Quantification of Mixtures of PDMS ligomer Distributions in PMMA matrix Name V 6140 /V 2200 (µl) M 6140 /M 2200 (Theoretical ) I t/2k / I t/6k (Calculated) Sample 1 50/ ± 0.86 Sample 2 40/ ± 0.23 Sample 3 30/ ± 0.05 Sample 4 20/ ± 0.04 Sample 5 10/ ± 0.03 Sample 6 0/ ± 0.00 Quantitative ToF-SIMS and MALDI of Polymer Surfaces utline Quantifying Amounts PDMS Impurities in Contact Lens (SIMS) Depth Profiles of Polymer Blends (SIMS) Quantifying Polymer Mw PDMS MW mixtures in PMMA (MALDI) Kinetics of PDMS polymerization (MALDI/SIMS) Quantifying Kinetics of Reactions (SIMS) Degradation Kinetics of Biodegradable Materials Simultaneous Drug Release/Degradation Kinetics 13

14 Anionic Ring pening Synthesis of Narrow Mw PDMS CH3 CH3 CH2 CH Li + CH3 CH3 Si CH3 Si Si CH3 CH3 CH3 D3 toluene/thf 35oC/8hrs CH3 CH3 CH3 CH3 CH2 CH [ Si Si - ]n Li+ CH3 CH3 CH3 CH3 CH2 CH [ CH3 CH3 CH3 CH3 CH3 CH3 Si - ] Si Li+ + CH3 Si Cl n CH3 CH2 CH [ Si ]n Si CH3 CH3 CH3 CH3 CH3 CH3 Anionic Ring pening Synthesis of Narrow Mw PDMS BuLi CH3 CH3 Si Si + CH3 CH3 Si cyclohexane CH3 CH3 D3 CH3 Bu Si Li + CH3 CH3 CH3 Si Li + Bu Si CH3 CH3 CH3 CH3 CH3 Bu Si Si Si Li + CH3 CH3 CH3 I1 I2 I3 THF D3 CH3 CH3 CH3 Bu Si [ Si ] Si Li + n CH3 CH3 CH3 CH3 CH3 CH3 CH3 Bu Si Si [ Si ] Si Li + n CH3 CH3 CH3 CH3 (CH3)3SiCl CH3 CH3 Bu[ Si ] Si n CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 Bu Si Si Si [ Si ] Si Li + n CH3 CH3 CH3 CH3 CH3 14

15 ToF-SIMS of PDMS ligomer Distribution Mw=2200 Mn/Mw = 1.05 Quantitative Data from Molecular Weight Distribution MnMw Mn=1730 Mw=1880 Mw/Mn= Counts (Ni) Molecular Weight (Mi)

16 MALDI Molecular Weight Distribution PDMS Intensity n = m/z ToF-SIMS of PDMS ligomer Distribution Mw=6140 Mn/Mw =

17 Quantitative Data from Molecular Weight Distribution n 3n-1 3n-2 Mn Mw Mn=6010 Mw=6220 Mw/Mn= Counts (Ni) Molecular Weight (Mi) MALDI Molecular Weight Distribution PDMS Intensity n = m/z 17

18 Quantitative Data from MALDI Molecular Weight Distribution MnMw Mn=6301 Mw=6546 Mw/Mn=1.04 Counts (Ni) n = M olecular W eight (M i) Change in Branching with Mw 18

19 N-butyllithium I1 I2 I3 Normalized Peak Intensities Time (hours) Sec-butyllithium I1 I2 I3 Normalized Peak Intensities Temperature ( o C) 19

20 pdms Polymerization Kinetics Conclusions Kinetics can be followed by Quant MS Polymerization Conditions can be optimized Reaction Products directly probed Initiator Populations Very Sensitive to Impurities Quantitative ToF-SIMS and MALDI of Polymer Surfaces utline Quantifying Amounts PDMS Impurities in Contact Lens (SIMS) Depth Profiles of Polymer Blends (SIMS) Quantifying Polymer Mw PDMS MW mixtures in PMMA (MALDI) Kinetics of PDMS polymerization (MALDI/SIMS) Quantifying Kinetics of Reactions (SIMS) Degradation Kinetics of Biodegradable Materials Simultaneous Drug Release/Degradation Kinetics 20

21 Introduction Polymeric Biomaterials Biodegradable Polymers Stable Polymers Uses: - Absorbable Sutures Uses: Joint & Tissue Replacements - Drug Delivery Devices - Scaffolds for Tissue Engineering Schematic of Degradation Process (a) Surface erosion (b) Bulk erosion (c) Erosion front formation Time in Water Time in Water Time in Water Erosion Zone Intact Zone Desirable Application : Drug Delivery Systems Desirable Application : Absorbable Sutures General ester hydrolysis mechanism CH 2 C CH 2 C H 2 CH C CH 2 C H H C C H H CH 2 C H

22 Surface Erosion vs. Bulk Erosion Characterization for Biodegradable Polymers Surface: Direct Contact Region with Physiological Environment Dictate in vivo Performance of Material Bulk Properties X Surface Properties Due to (1) Specific Molecular rientation at the Surface (2) Surface Specific Chemical Reactions Surface Characterization: Essential Value Fundamental Understanding of Hydrolytic Surface Degradation Mechanism & Kinetics Expanding into New Biodegradable Polymers Examples of Biodegradable Polyesters n n n R poly(glycolic acid) (PGA) poly(lactic acid) (PGA) poly(malic acid) R n n n poly(β-hydroxybutyric acid) (R=Me) poly(β-hydroxyvaleric acid) poly(δ-valerolactone) poly(ε-caprolactone) (CH 2 ) n n Poly(ethylene oxalate) (n=0) poly(malonate) (n=1) poly(succinate) (n=2) poly(ethylene phthalate) n 22

23 Polyglycolic Acid Results 23

24 Polyglycolic Acid Acid Results (ng + H + H + Na) + Plots of fragment peak intensities show the oligomer molecular ion peak distribution hr hydrolysis hrs hydrolysis Peak Intensity (arbitrary unit) X Title hrs hydrolysis hrs hydrolysis m/z 24

25 Polylactic Acid Results Polylactic Acid Results (nl + 2H + Na) + Poly(glycolic acid lactic acid) copolymer 25

26 Poly(glycolic acid lactic acid) copolymer Improving Quantitation by Integrating All Ion Formation Products: Possible Neutral Ion Dissociation and Fragmentation Pathways of Hydrolytic PGA Degradation Products ( [HCHR] + & C 2 ) * 19 m/z Mass Formula Assignment *18 * 17 - (H 2 & C) * A 1039 H-[CHRC] 17 -H---(Na)+ [CHRC] 17 -CHR ---(Na) + * (G17) A G (G18) Counts (H 2 ) A H-[CHRC] 17 -CH 2R---(Na) + H-[CHRC] 17 -Na---(Na)+ A G (G18) + (G17) AA + 17 BC B 1067 C 1069 [CHRC] 17 -CHRC ---(Na) + RCH 2 C-[CHRC] 17 -H---(Na)+ B G (G18) C G (G19) m/z * H-[CHRC] 18 -H---(Na)+ * (G18) 26

27 Quantitative ToF-SIMS Results Depending on Data Reduction Methods < Multiple Ion Summation vs. Single Ion Count > Multiple Ion Summation Single Ion Count Data Reduction Method Multiple Ion Summation Single Ion Count (A) (B) Calculation m/z Range Hydrolysis Condition Physiological Buffer : ISTN II (ph 7.4) 960 Hr Mn PDI DP Mn PDI DP ± ± Hydrolysis ± ± M n 900 ln[(dp-1)/dp] Condition ± ± ± ± ± ± Degradation k (hr -1 ) 2.67E E Kinetics R Hydrolysis Time (hr) Hydrolysis Time (hr) (A) Extent of changes in M n (B) Hydrolytic degradation kinetics Conclusions: Quantitative Methods Using Multiple Ion Summation Method, the Quality of MW Ave. Information about Polymer Biodegradation at the Surface has been Improved. This Method leads to a Better Data Reduction Method in Quantitative ToF-SIMS to btain Direct MW Information. This Present Work will be used as a Principal Tool for Surface Analysis of Biodegradable Polymers as a Function of Hydrolysis Treatment. 27

28 Using ToF SIMS, Conclusions : Direct Characterization of Hydrolytic Surface Degradation Mechanism & Kinetics of PGA in the Range of Hours Using DSC, : Chain Scission of PGA Related to Increase of Crystallinity From the combined ToF SIMS & DSC Results, Hydrolytic Degradation First in the Amorphous Region Increase of Crystallinity partly Determine Rate of Degradation Hydrolytic Degradation both at Surface and in Bulk ph Sensitive Potential Application of This New Approach : Simple, Fast, & Powerful Screening Test of New Biodegradable Polymers Degradation Kinetics Study of Biodegradable Polymers Conclusions Hydrolysis products of biodegradable polymers can be observed as intact molecules with ToF SIMS over a wide range; The data contained in ToF SIMS spectra, including molecular weight distribution of the hydrolysis products and molecular ion peak intensities, provides information to explore both reaction kinetics and mechanisms of the hydrolytic degradation of biodegradable polymers. 28

29 Quantitative ToF-SIMS and MALDI of Polymer Surfaces utline Quantifying Amounts PDMS Impurities in Contact Lens (SIMS) Depth Profiles of Polymer Blends (SIMS) Quantifying Polymer Mw PDMS MW mixtures in PMMA (MALDI) Kinetics of PDMS polymerization (MALDI/SIMS) Quantifying Kinetics of Reactions (SIMS) Degradation Kinetics of Biodegradable Materials Simultaneous Drug Release/Degradation Kinetics Application of the ToF-SIMS Method to Drug Delivery/Degradation Kinetics PLLA biodegradable polyester used. Ph 3 N used as an Insoluble Additive in aqueous buffer Media. Six different Blend Matrices of Ph 3 N/PLLA analyzed. (10:90 to 70:30 wt%) Degrade Blend Matrix (20:80 wt%) at two phs (7.4 and 10.0) for different time intervals. 29

30 MWD of Surface Hydrolytic Degradation Products of Ph 3 N/PLLA (20:80 wt%) Blend Matrices as a function of hydrolysis time Hr 12 Hr 18 Hr 36 Hr 42 Hr 48 Hr Counts m/z Hydrolytic Surface Degradation Kinetics of PLLA at the Surface of Blend Matrices (Ph 3 N/PLLA = 20:80 wt%) Hydrolyzed in Two ph Buffer Systems ph 7.4 ph 10.0 ph 7.4 ph M n ln[(dp-1) / DP] R 2 = k = -8.51E-5 R 2 = k cat = -1.70E Hydrolysis Time (hr) Hydrolysis Time (hr) k ph10.0 = 2.00 k ph7.4 30

31 Calibration Line and Resulting Release Profiles of Ph 3 N From Surface of Blend Matrices (Ph 3 N/PLLA = 20:80 wt%) Hydrolyzed in Two ph Buffer Systems Calibration Line ph 7.4 ph [Ph 3 NH] + / [C 3 H 4 ] R 2 = [Ph 3 NH] + / [C 3 H 4 ] :90 20:80 30:70 40:60 50:50 60:40 70:30 Blend Ratio (wt%) of Ph 3 N / PLLA Hydrolysis Time (hr) Comparison of Changes in Surface Concentrations 1.15 ph 7.4 ph Measured Relative Intensity Ratio [Ph 3 NH] + /[C3H4] A ph10 = -2.7E-4 A ph7.4 = -0.3E-4 40:60 30:70 20:80 Surface Concentration of Ph 3 N from Blend Ratio (wt%) of Ph 3 N / PLLA Hydrolysis Time (h) 31

32 Schematic of Drug Release Profile i Low MW Drug Incubation Development of Erosion Zone Water Penetration Hydration or Swelling Erosion Zone Induction Phase I nset of Polymer Degradation Decrease in MW Ave. Disorder of Drug Create Surface Micropores Induction Phase II nset of Drug Diffusion No Change in Polymer Weight Loss Initial Rapid Release of Drug Polymer Erosion nset of Polymer Weight Loss Decrease in Polymer Degradation Rate Schematic at the Initial Stage of Bulk Erosion of Biodegradable Polymer Blend Matrices Incubation Induction Polymer Erosion MW Ave. of Polymer Development of Erosion Zone t nset of Change in Degradation Rate Total Weight of Polymer Hydrolysis Time 32

33 Conclusions: Drug Delivery The Initial Rapid Release of Drug is observed in the Induction Phase of Bulk Erosion of PLLA. The Environmental ph effects the Rate of Initial Drug Burst as Hydrolytic Polymer Degradation is ph Sensitive. The Relative Initial Burst of Drug Release in Basic Conditions is more than twice (A ph10 9 A ph7.4 ) that of the corresponding Increase in Polymer Degradation Rate (k ph10 2 k ph7.4 ). The Drug Release is related to but not Singularly dependent on Polymer Degradation Kinetics. Emerging Applications of ToF- SIMS of Polymer Surfaces Imaging of Polymer Surfaces ligomeric Segments at Polymer Surfaces Reorganization of ligomeric Segments after exposure to water 33

34 ToF- SIMS Images of Teflon/Silicone Membrane Fluorine based signals Silicone based signals Proper Case for interpreting presence of different polymer membrane by complementary ToF SIMS images Note: Where there is a dark region in teflon image, there is a light region in silicone images H H 1,4-benzenedimethanol (BDM) + NC NC isophorone diisocyanate (IPDI) o C 2h - under N 2 HN C NH 2 H 2N (CH 2) 3 Si Si (CH 2) 3 CH p 3 amine terminated polydimethylsiloxane C NH polyurethane n THF/ under N 2 1) room temperature / 2h 2) 50 oc / 15h C NH NH C NH (CH 2) 3 Si Si (CH 2) 3 NH C p poly(ureaurethane)-pdms m NH HN C n 34

35 Mixture of Chains PDMS Reference Spectra G / m/z * o * 74 o 74 + * 74 o + * o + * o + * o m/z m/z 35

36 Apparent molecular weight distributions Pure G-3 and G-9 *-marked fragments 1.0 g9 g3 Normalized Intensity Segment Length Apparent molecular weight distribution information for high-mass range PDMS distributions Sample Structure (table 2) Apparent M n (1 st moment of distribution) Apparent M w (2 nd moment of distribution) 2 nd moment / 1 st moment (M w / M n ) G-9 * G-9 o G-3 * G-3 o

37 High Mass Spectra of Agglomerates Pure G3 50/50 G3/G m/z m/z Pure G m/z Proposed Structure of Ions in High Mass Spectra of Agglomerate Thin Films NH C NH CH 2CH 2CH 2NH C NH NH C NH (CH 2) 3 Si Si (CH 2) 3 NH C p m NH HN C n (3) + CH NH 2 or + (4) CH 2 NH 3 (1) CH 2 CH or (2) CH 2 GX PDMS Block 37

38 Comparison of High Mass Isotope Distributions to Support Ion Structure Assignment y = bx R = ± b = ± m/z m/z Spectra from Thick/Complete Films 38

39 AD Polymer System [ CH 2 C ] [ CH 2 C ] C= C= H 2 C=HCH 2 C CH 2 CH 2 CH 2 Si [PDMS] n CHCH 2 AMA DMS Is it possible to perform low temperature SIMS analysis and obtain high mass fragmentation? AD Copolymers Polymer PDMS Weight % PDMS M n PDMS M w /M n AD AD AD AD AD AD AD M n and M w determined by GPC 39

40 x SIMS Analysis AD7 Polymer Series - Dehydrated Counts m/z M n = 2090 M w = 2225 PDI = Counts m/z [ CH 2 C ][ CH 2 C ] C= C= H 2 C=HCH 2 C CH 2 CH 2 CH 2 Si [PDMS] 25 CHCH 2 C= CH 2 CH 2 CH 2 Si [PDMS] 24 Si CHCH H

41 References Christine M. Mahoney and Joseph A. Gardella Jr., Determination of Surface PolyDimethylSiloxane (PDMS) Segment Molecular Weight Distributions in Poly(ureaurethane) PDMS Copolymers using Time of Flight Secondary Ion Mass Spectrometry, Analytical Chemistry, submitted, December C. M. Mahoney and Joseph A. Gardella, Jr., Determination of oligomeric chain length distributions at surfaces using ToF-SIMS: segregation effects and polymer properties, Applied Surface Science, Proceedings of the 14th International Conference on Secondary Ion Mass Spectrometry, 2004, in press. Joo-Woon Lee, Jinxiang Yu, Joseph A. Gardella, Jr., Wesley L. Hicks, Jr., Robert Hard, and Frank V. Bright, Phase Separation at the Surface of PE-containing Biodegradable PLLA Blends and Block Copolymers, Langmuir, Submitted, December Adam M. Hawkridge and Joseph A. Gardella, Jr., Mass Spectral Investigation of the sec-butyllithium and n-butyllithium Initiated Ring-opening Polymerization of Hexamethylcyclotrisiloxane (D3) Journal of the American Society for Mass Spectrometry, 2003, 14 (2), Wen Yan Yan, T. D. Wood and J. A. Gardella, Jr. Quantitative Analysis of Technical Polymer Mixtures by Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry Journal of the American Society for Mass Spectrometry, 2002, 13, References Joo Woon Lee and Joseph A. Gardella, Jr., "Simultaneous ToF-SIMS Quantitative Analysis of Drug Surface Concentration and Polymer Degradation Kinetics in Biodegradable PLLA Blends", Accelerated Article, Analytical Chemistry, , Joo Woon Lee, Wesley L. Hicks, Jr., Robert A. Hard, Frank V. Bright and Joseph A. Gardella, Jr., Analysis of the Initial Burst of Drug Release coupled with Polymer Surface Degradation, Pharmaceutical Research, 2003, 20(2), Joo Woon Lee and Joseph A. Gardella, Jr., Quantitative Time of Flight Secondary Ion Mass Spectrometry Analysis of ligomeric Degradation Products at the Surface of Biodegradable Poly (α- Hydroxy Acid)s, Journal of the American Society for Mass Spectrometry, 2002, 13, Joo Woon Lee and Joseph A. Gardella, Jr., Surface perspectives in the biomedical applications of poly(α-hydroxy acid)s and their associated copolymers, Analytical and Bioanalytical Chemistry David M. Hercules Festschrift Issue, 2002, 373, J. W. Lee and J. A. Gardella, Jr. In-Vitro Hydrolytic Surface Degradation of Poly(glycolic acid): Role of the Surface Segregated Amorphous Region in the Induction Period of Bulk Erosion, Macromolecules, 2001, 34(12), J.-X. Chen, J. W. Lee, N. L. Hernandez de Gatica, C. A. Burkhardt, D. M. Hercules and J. A. Gardella, Jr., "Time of Flight Secondary Ion Mass Spectrometry Studies of Hydrolytic Degradation Kinetics at the Surface of Poly(glycolic Acid), Macromolecules, 2000, 33(13), J.-X. Chen and J. A. Gardella, Jr., "Time of Flight Secondary Ion Mass Spectrometry Studies of in-vitro Hydrolytic Degradation of Biodegradable Polymers, Macromolecules, 1999, 32(22),

42 Conclusions Detailed Quantitative Approaches can yield in-depth structure which correlates with practical performance Quantitation can influence polymer synthesis and design New methods can evaluate reaction kinetics at surfaces Mass Spectrometry is ripe for development for quantitative analysis 42