infrared microscopy and microanalyses for hire: analytical lab for small companies

John Donohue - [email protected]

Chemical Microanalysis for Industry

State-of-the-Art Analysis for hireMedical Device Problem Solving

Polymer Problem SolvingIndustrial Problem Solving

Asbestos Analysesetc., etc., etc. by

John Donohue201-294-2581


Hello. I’m John Donohue and this is the best Infrared Microscope ever made byany manufacturer: Nicolet’s IR-Plan Research Microscopemounted on a Magna 560 Mainbench

This amazing instrument allows my Labto obtain the Chemical Identity, via the Infrared Spectrum, of an area as small as 10 microns by 10 microns (10μX10μ). That’s as small as 9 red blood cells placed in a 3X3 square.

When you can chemically identify objects that small you can perform such amazing investigations that theycan often depart completely from the expected and traditional uses of Infrared Spectroscopy, as you will see.

These documents will describe the type of analyses I perform for Industry and Publication using this instrument and the other equipment in my Laboratory.

Part 1: Introduction to the Technology and Method


Mirrored “Lampshade”

Mirrored “Flying Saucer”

Hard Silicon Surface for ATR “Contact” Spectra

My IR-Plan is usually set up with Two Reflachromats:One For Reflection And Transmission, The Other Dedicated To ATR

More “Specialized Reflachromats” and Visible Light Objectives are available, if needed

… and Visible Light Objectives forVisible and Polarized Light Microscopy


Microscope Reflection ModeLightpath

The Upper Reflachromat objective projects a conical surface of IR radiation through the sample. It reflects off the shiny metal beneath the sample and follows the same conical surface up through the sample, back to the objective, and from there to the detector.

This mode is very fast and easy to perform. The shiny metal substrate is usually 0.005 inch aluminum sheet taped onto a microscope slide. It is cut from 5 inch by 5 inch sheet that is cheap and disposable. It can also be performed on any flat or curved metal surface such as injection molding tool surfaces, medical steel cannulas, engine valves, gun metal, you name it.

To Detector

From Source

Sampleon metal

Shiny Metal Substrate

Shiny Metal Substrate


>The FTIR Microscope increases greatly the utility of FTIR and allows the successful use of IR in analyses that simply could not be done by a Mainbench alone.

>The Micro - ATR Objective obtains surface spectra (of the top ~micron of material) with almost no sample prep. This is excellent for thin coatings or surface analysis.

>The FTIR Microscope can obtain useful spectra from extremely thin samples as small as a 10μ X 10μ Square. The amount of mass providing such a signal can approach the Detection Limits of GC/MS

>Example - FTIR Microscope’s Limit of Detection is about a 10μ X 10μ Square : If sample is 1μ thick, 10μ X 10μ X 1μ sample of Polyethylene = how many grams? 1cc of PE = 1g = 10mm X 10mm X 10mm = 1000 cubic mm = 103 mm => 10mm X 10mm X 10mm = 104 μ X 104 μ X 104 μ = 1012 cubic microns => So: 1012 cubic microns = 1g

10μ X 10μ X 1μ =100 cubic microns = 102 cubic microns 102 / 1012 = 10-10 g So: 10μ X 10μ X 1μ sample of Polyethylene = 0.0000000001 grams of PE

So, the FTIR Microscope can ID 100 trillionths of a gram of PE

UNIQUE ADVANTAGES OF THE FTIR MICROSCOPEHow sensitive is it? See arithmetic below.


Microscope ATR Mode and LightpathThe ATR Reflachromat objective projects a conical surface of IR radiation onto the inside of the ATR Crystal’s Sample Contact Point. A small part of the IR radiation “tunnels” into the sample touching this Contact Point. Some of it is absorbed and the rest continues on to the detector.

This mode is particularly well-suited to surface analysis (surfaces that are bioactive, drug eluting, bioresorbable, coated, “blooming” additives, lubricious, non-thrombogenic, etc.).

It is also a good choice for highly absorbing materials that are difficult to get an IR beam in and out of such as Black Rubber.

From Source

To Detector

Sample Sample


How Small Can Samples Be?How small IS the 10μ X 10μ Limit of Detection?


Back of USA Penny

LincolnMemorial


Lincoln seated on Penny’s back

This image is 11.2mm X 8.5mm.


Lincoln seated on Penny’s back; mm scale to left

This image is 3.0mm X 2.3mm.


IR-Plan Visible Light 10X Objective view (Glass)Lincoln’s Head and Shoulders

This image is 550μ X 420μ


IR-Plan IR Objective 15X Reflachromat view: Lincoln’s Head

This is the magnification at whichKnife-edge apertures are used to frame

the area to be analyzedand FTIR Spectra are obtained.

10μ X 10μ

This image is 390μ x 300μ

Limit ofDetection:

“Lincoln’s “Eye”

Lincoln’s Face on the previous slide is about 140μ X 120μ.The IR-Plan can obtain good spectra from much smaller samples than this (see asbestos ribbon, below). The thin polymer coating on Lincoln’s Face is easily IDdas Polycarbonate.



Asbestos Identificationby IR Microscopy and/or

Polarized Light Microscopy

Part 2: Asbestos Testing

Friable Asbestos Identification by IR Microscopy of broken cementitious tile:



Zooming in on the Friable Asbestos


Microscopic amount of Asbestos squashed onto aluminum sheet


NOTE: Often Spectra are corrected for humidity in the Laboratory air


The Asbestos sample is Chrysotile


The IR Microscope is so very sensitive that even a 20μ X 65μ areaof a Single “ribbon” of Asbestos is enough for Identification


Asbestos Identification and Quantificationis routinely performed as per

EPA-600-R-93-116 usingPolarized Light Microscopy (PLM)

Examples of PLM in my LabsMaterials Analyses follow


>These barrels were for “EpinephrinePens” needed to counter the threat ofNerve Gas and thus keep Saudi Arabiafrom backing down to Iraq in the GulfWar. This allowed the USA to Stagethe invasion of Kuwait.

>The barrels were breaking 100% uponejection from mold with undercut. >Defect invisible until Crossed Polarizersrevealed “Knit Line” pointing toCrack Initiation Point.

>The molten plastic was too cool whenIt came squeezing around the Core Pinfor the two advancing Melt Fronts tomelt together adequately.

>I told Manufacturer to increaseZone Temperatures by 30 degrees Cand Ejection Breakage ceased. ... and that’s how I won the war.

Device ProductionRestarted and DefectDetermined and EliminatedVia Stress BirefringenceAnalysis

CrackInitiationPoint


Polypropylene Syringe Wall Cross SectionControl of Cooling Rate is a major parameterin Determining Morphology and Properties

This type of work was very important in the implementation of Clear Polypropylene Devices using Milliken Clarifying Agents that have theundesirable effect of increasing the brittlenessof Polypropylene.

Polypropylene Syringe Gate Cross SectionControl of Rheology is a major parameterin Determining Morphology and Properties

This type of work was also very important inthe implementation of Radiation Sterilizationwhich also has the undesirable effect ofincreasing the brittleness of Polypropylene.

Injection Molding Morphology and Physical Properties


Solving Medical Device problems using

IR Microscopy

Visible Microscopy

Part 3: Application to Medical Device issues


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Silicone Lubricated Gasket

Less Silicone After Surface Scraped

No Silicone After Acetone Wash:Silicate-filled rubber polymer

ATR Spectra of Surface of IR-Opaque Rubber

2.3mm x 3.0mm Photos of an Insulin Needle Point

The Technology of a Needle Point

What can we learn with a fast analysis?John Donohue - [email protected]

420μ x 550μ Photos of Needle’s three cut planes

The “subtle” cutJohn Donohue - [email protected]


IR-PLAN 550μ X 420μ FOV of Point and Enhanced Image

Raw Image Obtained

Digital Enhanced Image

A “Metal Burr” is visibleon this needle point.


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Infrared Microscopy Provides Chemical Identification that showsGelled Lubricant is used on Hypodermic Needles

3.0mm x 2.3mm

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390μ x 300μ

Gel is Silicone

8.5mm X 11.2mm

Hoop Stress cracking

Polyetherimide (PEI) Stopcock Outerbody resists splitting caused by fatty Feeding Liquids but costs more than Polycarbonate (PC) (which is cracked by combination of fats and stress). Stopcock InnerBody is pressed into Outerbody and this strong PEI polymer can still crack if it can’t stretch enough under this “Hoop Stress”tensile load (vs PC which is very stiff but also very TOUGH/RUBBERY).

Engineering Resins: ESCR vs “Hoop Stress Failures”



PET Barrels That Failed At Gate

A “Cold Slug” in an Injection Molding “Gate”can initiate breakage at unacceptably low force


Gate A Gate B Ridge/Valley

Cold Slugs

Blade Striations

Devices broke due to “Cold Slug” in Injection Molding Gate


Identification of PET Barrel SkirtContaminant by Micro-FTIR


Smudges on PET at Tip Insert of Barrels

Parting Line

Pre-Extracted Cellulose on PET Skirt Same Area of PET Skirt After Wiping

Streaks where Greasewas removed

Cellulose

Grease aboutto be removed

PET Barrel Skirt Bloom removed for analysis


5 .S ilic o n e B B L L u b e A T R ,B ra d m o n s

K im w ip e d B lo o m in P E T B B L s k irt,G riffith ,R E F L 3 2

P E T B B L s k irt g re a s e ,K im Wip e d & M C d ,C a s tro ,R E F L 3 2 ,2 /2 7 /0 9

1 2 0 a 2 2 0 9 ,M IC R ,C E L L U L O S E ,A C C U WIP E /A L ,2 /2 4 4

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Silicone

Cellulose

Grease Found Previously

Grease Found Recently

PET Barrel Skirt Contaminant is Same as Found previouslyThe Difference Seen below is Cellulose from the Kimwipe.

The Grease is an Acid (1712 cm-1) and an Ester (1737 cm-1).



An unusually profitable Bioresorbable Implant with a brilliant Market-dominating future had its Market Launch endangered by the occurrence of foreign matter inside the tiny molded PolyLactide:Glycolide implant. A CERTAIN fix was required immediately: the cause had to be IDd with certainty and eliminated.

Many Hypotheses were proposed:

>The Resin Supplier suggested that Residual Monomer was boiling during molding. Extensive testing of residual monomer levels in retained lot samples vs amount of bubbles found from molding those lots was proposed.

>Molding Engineers suggested that the bubbles were: Shrink Voids, Entrapped Air, Entrapped Condensation, Etc. Humidity archives were to be examined and production areas were to be desiccated.

>”Shotgun Experiments” were about to be fired in every direction.

Instead a “RIFLE BULLET” EXPERIMENT was aimed right at the bubbles themselves.

>Contaminant was Bubbles Inflated while Flowing “COMET”.>Cut thin Cross-sections of the polymer through the Bubbles.>Micro-FTIR repeatedly found a single deposit of Secondary Amide localized in a small area on each Bubble’s inner surface.

Part 4: Nailing the Answer and Preventing a Recall

FlowDirection


Hazy TranslucentArea on border ofBubble

When a thin slice of the Part, containing the Bubble, was shaved off,the Hole in the shaving had a tiny region on its circumference

that was Hazy Translucent while the rest of the circumference andof the part’s shaving was Clear Translucent

Cross-section of Bubble

Clear translucent polymer slice


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“Zooming in” on Hazy deposit on Bubble’s circumferenceIncreases the Secondary Amide Absorbance Peaks relative to the PLG’S...

PLG

PLG

...therefore the hazy area is a Secondary Amide

FTIR Microscopy

Zooming in


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Three Amide deposits on Aluminum with PLG dissolved away. Two Amide deposits squashed onto Aluminum.

Methylene Chloride removedmost of the PLG

Squashed onto Aluminum

Squashed onto Aluminum

AmideAmide

... so what is this Secondary Amide and what is it doing?


Synergistic Use of

FTIR Microscopeand

Gas Chromatograph / Mass Spectrometer

The two most powerful instrumentsIn Analytical Chemistry

... so what is this Secondary Amide and what did it do?


The SIS Thermal DesorberA Heated Inlet for GC/MS

sold by Scientific Instrument Services


Carrier Gas Flowpath to Mass Spec Detector

Pure He flowing throughglass lined steel tubethat contains sample.

Tube is injected intoGC Inlet and heated.

Volatiles separate oncolumn and are analyzedby the MS.

Excised tiny intact Bubbles melted in THDSBpop and release CO2 (and NOT O2 or N2)

PLG Hydrolysis in heated tube releases Lactide and Glycolide


Hydrolysis of PLG: The Chemistry Occurring

The moisture in the amide flakesforms steam during injectionmolding, inflating the bubbles.

The steam is consumed as ithydrolyzes the PLG, filling thebubbles with CO2.

as per Dr. C. C. Chu of CornellJohn Donohue - [email protected]


Spectral changes of PLG hydrolyzed on Hotplate

Carbonyl and Hydroxyl orbitalsare formed as the controlshydrolyze on the hotplate.


Spectral changes of PLG vs proximity to amide deposit

The concentration of the same Carbonyland Hydroxyl orbitals is seen to increasewith increasing proximity to the bubblesformed by the amide flakes. This largegradient in concentration occurs acrossa microscopic range of distance from thebubbles’ walls.

It is in analyses like this one that theFTIR Microscope is the very best toolthere is. No other instrument coulddo this work: easy and exact spatiallocalization of a chemical identification.


Preventing Recall - Conclusion>Skin Flakes boiled off their water, inflating the “comets”

>As this steam inflated the PLG, it was immediately consumed by the PLG’s Hydrolysis Reaction

>Hydrolyzing PLG emits CO2, the gas remaining inside the “comets” that was detected by GC/MS as the “comets” melted and popped

>Hydrolyzing PLG on a hot plate using drops of water Darkened spots ranging from light brown to nearly black

>FTIR spectra of these darkened regions peaks appearing near 1730 cm-1 and 1620 cm-1

>FTIR spectra obtained from microscopic regions as the area examined approached the hydrolyzed circumference of the “comet” slices peaks appearing near 1730 cm-1 and 1620 cm-1

>The polymer pellets were protected against any further contamination by skin flakes, there was no further problem with “comets”, the product launch was continued, and the implant dominated its market One Billion $ in $ales per year


Ending $100MM/yr Device Factory Shutdowncaused by “wrinkled” Injection Molded Parts

A $100MM per year device factory was shutdown because Injection Molded parts were slightly wrinkled. No one was going to make any money until the problem was fixed.

Possible causes that were proposed for investigation: >Electrical supply fluctuations >Cooling Water Heat Transfer fluctuations >Press Horsepower fluctuations

Many “Shotgun Experiments” were about to begin with no expense to be spared

--- BUT ---

>The Polypropylene (PP) Resin was supposed to contain Sodium Benzoate (NaBZT), an additive that makes the Polymer solidify at a higher temperature (faster) than normal.>This fact suggested that the best place to look for the cause was in the PP pellets themselves.>I developed an Infrared analytical method that measured very quickly the NaBZT concentrations of large numbers of individual pellet.


Plant Shutdown Ended“Wrinkled” Injection Molded Parts caused by Resin Supplier’s Error

FREQ

NaBZT Concentration

This is one example of when to use the FTIR Mainbench instead of the Microscope:When you want to analyze as large of an area as possible per each scan.

>The Resin Supplier by mistake had added different pellets to the Finished Material: pellets that contained a significantly higher concentration of NaBZT than the correct pellets. These wrong pellets were dumped into the Railcar on top of the correct Resin.

>The resulting mixed resins received only the little bit of blending that occurred during transport from the Railcar to the Silo and then to the Hoppers.

>The Parts wrinkled because the varying NaBZT concentrations caused varying degrees of Shrinking and Packing during molding.

...but some had too much

Analytical Method developedto measure RAPIDLY theConcentration of individual pelletsproving Bimodal Distribution

Most Pellets hadRight NaBZT amount


FTIR Microscopy can do a lot morethan the simple chemical

identification of contaminants.

> It can determine the physical morphology of polymers.

> It can measure the oxidative degradation caused by radiation sterilization (dosimetry).

> It can measure the hardness of PVCs, Polyurethanes, and numerous other Thermoplastic Elastomers

> It can measure the Butadiene or Styrene content of Styrenics

Part 5: Special Applications


Measuring Changes in Crystallinity:PET Tube Turned Opaque White

Customer complained that PET catheter was opaque white instead of clearBUT

Had the customer accidently left this catheter in a hot Autoclave overnight?

Polyethylene Terephthalate Crystal Structure



The Mettler Hotstage

Remove the glass window and insert a strip of aluminum sheet or a thin, “homemade” KBr “poker chip”.Then you can obtain spectra while heating the sample.


Spectral Differences Between Clear And Hazy PET TubesCrystallinity Peaks marked in Hazy Return

FullSpectrum

zoom in

The hazy (opaque white)catheter had spectraldifferences whencompared to the clearcatheter (crystallinity peaksare shown at right)


When the clear tube was quenched from the melt by Boiling it in Water, it crystallized, turning white like the Customer’s Hazy returned tube.

Proof that Spectral Differences Between Clear and Hazy Tubesare due to Crystallinity

Crystallized in Boiling Water

Crystallized in Boiling Water

The Spectra of the clear tube whenit is molten at 260C is the same aswhen it is quenched from the meltby Liquid Nitrogen.BUT when it is quenched from themelt by Boiling it in Water, itanneals and grows crystals.

Crystallized by Customer’sUnknown Method


Proof that White catheter has hydrolyzed to Lower Molecular WeightWhen the Clear tube, a PET controlsample, and the Hazy PET weremelted and then instantly quenchedfrom the melt in Liquid Nitrogen, theHazy sample has already Crystallized.and the Clear tube sample has not.

The Hazy PET crystallizes much morereadily because it has Hydrolyzed toa Lower Molecular Weight.

When the clear tube is melted andkept (quenched) in ambient air for4 seconds or 10 seconds before beingquenched in Liquid Nitrogen, NO crystallization begins after the 4seconds in air and only a tiny amountafter the 10 seconds in air.

The Hazy PET crystallizes much more readily because it has Hydrolyzed to a Lower Molecular Weight.The Customer probably left the catheter in a hot Autoclave overnight.


Effects of Radiationand Accelerated Aging

Part 6: Radiation Sterilization Issues

ATR Spectrum

Reflection from smearon aluminum sheet

The bloom visible on this catheterwas analyzed both by contactingits surface with the ATR Objectiveand by smearing the bloom ontoaluminum sheet and analyzingthe smear by Reflectance.The smear shows only the DEHPwhile the ATR sees both theDEHP and the PVC catheter.

Radiation Increases PVC BloomingOf Cytotoxic DEHP Plasticizer



Radiation Generates Free Radicals in Polypropylene


Free Radicals Generate Carbonyl Groups in Polymers


Test Method DevelopmentDecreased Ductility Can Cause Devices To Break During Use.

Radiation may increase the force to strain the device, but the strainat break decreases. Devices seldom fail because they’re too stiff.

They fail because they break.

A Syringe barrel wall may be unbreakable during use despite receiving the highest radiation dose allowed. Syringe tips may be much more fragile. Customer complaint history and product history may indicate what areas of a product are areas of concern; what are the products’ weakest links. It is these modes of failure that must be tested.

Testing must mimic the mode of failure expected during customer use. Breakage tests must be performed at a speed of deformation similar to that experienced by the product during customer use.

Testing samples subjected to Accelerated Aging will provide data quickly that predicts the future behavior of products. The Test Protocols will define the Accelerated Aging to be used.

Measuring Radiation Damage using Micro-FTIRMounting Aluminum Sheet On 3X2 Glass Slide



Shavings off Polypropylene Barrel’s Surface Analyzed Herein:Shavings Obtained with Razor Blade

Close-ups of Polypropylene Shavings Analyzed Herein



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Same Polypropylene Film Before and After 40 kGYs of Cobalt RadiationBlue is after


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Hydroperoxides Carbonyls


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Scissioned Polymer Chains Oxidize


IR Spectrum Shows Radiation Induced Oxidation of Polypropylene

as per J. Donohue MDDI


Polypropylene Oxidation from 20 and 40 kGYs of Cobalt Radiation


The “Dark Reaction” of Irradiated PolypropyleneOxidative Degradation Continues Long After Irradiation Has Ceased

This is the Reaction that is Accelerated by Accelerated Aging


Dr. Apostolou and I “wrote the book” on Accelerated Aging Methods that work


Oxygen Can More Easily Penetrate and Reactwith the Polymer in a Thin Film


This Post Rad Oxidation is Not Just Peroxide Scissions. Ambient Oxygen Continues to React with the Polymer.

This is Proven by this Vacuum Oven Aging.

Polyethylene Undergoes Similar Oxidationwhen Irradiated with 20 and 40 kGYs



A Carbonyl Index Can be Defined to Measure this Oxidation


Statistical Results for Micro-FTIR Dosimetry of Gamma vs ControlThe Micro-FTIR Method is Accurate, Precise, and Robust


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X = Thickness of slice (area of 1304 cm-1 Absorbance)

Area of C=OAbsorbancedivided by X

(Carbonyl Index)

Radiation Damage (= Dose) Measured for Thin Surface Shavings of Sterilized Polypropylene Medical Devices

Shavings of samples with 0 Mrads

Shavings of samples with 3.5 Mrads

Shavings of sterile product

Shavings of underdosed product

FTIR Microscopy can determine a competitor’s dose or detect underdosed non-sterile devices.


Stability of Fina Syndiotactic and IsotacticPolypropylenes to Cobalt Radiation

and Accelerated Aging


Ziegler-Natta and Metallocene Catalysts

Controlled Orientation of Monomer Approach To Active Site Yields Controlled Stereoregularity of Polymer Chain Formed.For Z-Ns, Solid Catalysts Control Approach to Active Site.For Metallocenes, Molecular Structure Controls Approach.


Stereostructure of Isotactic Polypropylene

Hydroperoxide Formation by “Backbiting” Oxidation

Strings of Close, Unstable, Pendant Hydroperoxides

Free Radical Degradation of Isotactic Polypropylene


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Isotactic Polypropylene Before and After 38 kGy & 17 Days @ 70 C

Hydroperoxides Carbonyls

The Isotactic Polymer is extensively Oxidized by Irradiation. It sizzles like bacon when it is melted.


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Syndiotactic Polypropylene Before and After 38 kGy & 17 Days @ 70 C

The Syndiotactic Polymer exhibits very little Rad-induced Oxidation


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IPP & SPP: 38 kGy & 70 C Aging StudyAccelerated Aging Increases IPP Oxidation

but has Very Little Effect on SPPIPP @ 70 C: 17 Days 88 Hrs 16 Hrs 0 Hrs

IPP 0 Dose

SPP 0 Dose

SPP @ 70 C:0 to 17 Days


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IPP & SPP: 38 kGy & 40 C Aging Study

IPP @ 40 C: 17 Days 88 Hrs 16 Hrs 0 Hrs

IPP 0 Dose

SPP 0 Dose

SPP @ 40 C:0 to 17 Days

Accelerated Aging Increases IPP Oxidationbut has Very Little Effect on SPP


Carrier Gas Flowpath to Mass Spec Detector

Pure He flowing throughglass lined steel tubethat contains sample.

Tube is injected intoGC Inlet and heated.

Volatiles separate oncolumn and are analyzedby the MS.


Radiation SterilizedSyndiotactic PolypropyleneGenerates an Order ofMagnitude Less Volatilesthan an Equal Mass ofIrradiated Isotactic Polypropylene

THDSB/GC/MS Analysesof Post-Rad Volatiles

John Donohue - [email protected] Close, Unstable, Pendant Hydroperoxides Explode Like a String of Firecrackers

CO2acetaldehyde

acetoneacetic acid

4-hydroxy4-methylpentanone

2,4-dimethylfuran

cyclopropylacetone

allylacetone

acetic anhydride

3,5,5-trimethylfuranone

acetoacetone

THDSB/GC/MS IDENTIFICATION OF IPP POST-RAD VOLATILES

Heated Irradiated Isotactic Polypropylene Degrades into Volatiles Based on C-C-O Units that Reveal the Chemical Mechanisms of its Oxidation


Thermally Degraded Post Rad Isotactic PolypropyleneEmits Low Mass Scission Products Based on C-C-O Units …

Air & WaterDesorbed OutOf Tube

Acetone

Acetic Acid

… Because Similar Oxidized Structures Degrade into Similar Volatiles

THDSB/GC/IR Analyses of Post-Rad Volatiles

Thermally Degraded Post Rad Syndiotactic PolypropyleneEmits a Far More Random Mix of Scission Products …

Air & WaterDesorbed OutOf Tube

2-Hydroxy-Propionic Acid

3-Methyl-2,4-Pentanediol

4-Butyl-Gamma-Octanolactone

… Because a More Random Dispersion of Oxidized Structures Yieldsa More Random Mix of Volatile Degradation Products

THDSB/GC/FTIR Analyses of Post-Rad Volatiles



Phenolic Antioxidants Protect Against Radiation Damage by Scavenging the Free Radicals Formed in the Polymer by Radiation

Part 7: Additives; their Analysis and Issues


But Phenolic Antioxidants Turn Plastic Yellow When Irradiated


Hindered Amine Light Stabilizers Form Cytotoxic Hydroxylaminesas they Protect the Polymer from Radiation Damage

Without Discoloration


Millad 3988 Clarifies PolypropyleneMolding Heat Causes Hydrolysis, Releasing Benzaldehyde Derivatives

This Causes the Polymer to Emit a “Cherry Candy” SmellMillad makes Polypropylene more brittle

Clarified Polypropylene Crystallized at 130 C from the MeltNucleation Determines Morphology

ClarifiedNot Clarified

Sublimation depletes Boundary of MilladPolypropylene Spherulites grow

Millad preventsSpherulite growth



Millad Forms Thermally Unstable Precipitate if it is Overheated DuringInjection Molding. Precipitate’s Sizzling Decomposition into Gaseous,

Superheated Aldehyde Strips Char out of Molding Press and Into Molded Parts. Heated excised precipitate chunks undergoing thermal decomposition on Hotplate


Sizzling Decomposition into Aldehyde and Arylate

>Tiny orange spots were scattered across the Polypropylene matrix

>Any attempt to get the spectrum of more than one orange spot at a time yielded only a spectrum of the Polypropylene matrix

>But the IR-Plan can can zoom in on a single tiny orange spot to yield the Arylate spectrum shown …

… and Thermal Desorption of the degrading material into the GC/MS can show the formation of the Aldehydes and Alcohol Intermediates.


Thermal Decomposition of Precipitate Forms Aldehyde.Cannizzaro Reaction of Aldehydes Forms Acid and Alcohol.

Condensation of Acid and Alcohol Forms Arylate.

Arylate Forms The Orange Spots


Thin Layer Chromatography (TLC) can Separate Chemical Mixtures that theGC/MS can’t: Chemicals that are non-Volatile or Thermally Unstable

Liquid carries chemicals in spot of extract up the plate, separating them


>TLC is done on a Plate Covered with Fluorescent Silica>UV Light makes the Separated Chemicals from the Mixture Visible>The Regions of Silica Containing these Chemicals are scraped off the plate, separated from the Silica, and Identified using the Analytical Instrumentation

Under Visible Light

Under UV Light

After Scraping

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Measuring Durometer of FINISHED (competitive) Devices:FTIR of DEHP Plasticized PVC Device vs Pure PVC

Pure PVCDEHP

Part 8: Tricks of the Trade



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FINISHED Device: Measuring Plasticized PVC Durometer

Hard Endotracheal Tube

Soft Nasogastric Tube

DEHP

PVC

Spectra “normalized” for equal plasticizer (DEHP) content showthat the harder PVC has a higher PVC to Plasticizer RatioSuch a test can tell the Durometer used by a Competitor

HigherPVC

conc.


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Reverse engineering competitive cathetersMicro-FTIR Spectrum of Pellethane

zoom in here next slide


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Micro-FTIR ID: FINISHED Device Pellethane Durometer

80A

90A

75D

>Many catheters have tips made from a softer grade material than the shaft.

>FTIR can measure the Durometer of finished Polyurethane devices quickly and easily

>Multiple runs below show that the method is robust


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Micro-FTIR Spectrum of Tecothane



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Micro-FTIR ID: FINISHED Device Tecothane Durometer

74A

85A

55D

75D


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Micro-FTIR Spectrum of Tecoflex with 20% BaSO4



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Micro-FTIR ID: FINISHED Device Tecoflex Durometer

80 A

85 A

100 A

65 D

60 D

NOTE:This method is more accurate than themanufacturer’s ability to control or measuretheir Durometer. The Hardness Pucks thatwere supplied by the manufacturer (aftermeasuring Durometer with a Hardness Tester)and were supposed to be 60 D were insteadHARDER than the supposed 65 D pucks.


HIGH-GLOSSABS CRACKS

LOW-GLOSS ABSRESISTS CRACKING

FTIR Shows Why High-Gloss ABS Has Less ESCR Than Low-Gloss ABS

More Styrene/Butadiene Rubber dispersed in the Acrylonitrile matrixyields High Gloss ABS with less resistance to Environmental Stress Cracking


Packaging Materials

>There are a lot of “Tricks of the Trade” in Materials Analysis.

>For example, Most packaging films are laminates with outer heat-sealable plies and an inner strength ply.

>The FTIR Microscope requires Liquid Nitrogen (LN2) to operate and this LN2 can be used to cryo-fracture materials.

>Cryo-fractured laminated films can be separated easily into their individual plies for material identification and also for accurate thickness measurements free from thickness artifacts caused by cutting techniques that can decrease the measured thicknesses.


The film contains K-Resin…

…and the stretched Heat Seal Ply is EVA

Device package bottom web wascryo-fractured with liquid N2 andthe heat seal ply was stretched over aluminum sheet.

Device package bottom web wascryo-fractured with liquid N2 andthe protruding and overhangingplys show a Surlyn center plysandwiched in EVA heat seal plys.

Surlyn center plyprotruding fromfractured laminatedfilm

Surlyn ply and EVA heatseal ply together



Device package bottom web wascryofractured with liquid N2 andthis two ply film separated intoa K Resin ply and a more flexibleEVA heat seal ply.

K Resin ply is stiffer

EVA heat seal ply


Chemical Degradation of Polycarbonateby Dymax Adhesive

Analysis of White Stain inside Cured Part

Part 9: UV Adhesives and the Chemical Fragility of Polycarbonate


ABSTRACT>Polycarbonate (PC) has poor resistance to attack by a large number of chemicals.>Chemicals that “plasticize” PC cause problems that include clouding, warping, crazing, cracking, breaking, falling apart, etc. For example, Formula 409 contains about 10% “grease cutter” and will quickly destroy PC; especially when the PC has a relatively low Molecular Weight and/or lots of molded-in-stress pulling it apart.>Chemicals that are “Bases” (electron donators) catalyze the polymerization of PC and therefore can also catalyze the reverse reaction, depolymerizing PC into oligomers of Bisphenol A (BPA) monomer or the BPA monomer itself. For example, Amines famously do this to PC.>A major ingredient of the Dymax adhesive is N,N-Dimethylacrylamide (a base). It is well-known that many adhesives will attack PC if they are in contact with it too long prior to being cured. This chemical is one of the reasons for this. When the adhesive is completely cured, this chemical is completely consumed (this fact is demonstrated using the spectra herein).>The white stain on the PC in contact with the “cone” of adhesive is partially depolymerized PC. Its FTIR spectra show the presence of both PC and the endgroups (that appear as BPA and its oligomers) are formed from the scissioning of PC. The adhesive must be quickly and fully cured to prevent this.>The side of the adhesive cone that was peeled free from the PC is coated with a thin shattered film of PC. The side that was in contact with the Polyurethane (PUR) is coated with the PUR. Thus, the adhesive is tougher and more tenacious than either polymer.


What Happened to the Polycarbonate?


White Stain Seen Through the PC Wall Prior to DissectionWhite Stain is Connected to the PC


White Stain Remains on PC After Adhesive is Peeled Back

PolycarbonatePeeled-backDymax Adhesive

Polycarbonate


White Stain Remains on PC Higher Magnification

Polycarbonate Polycarbonate


White Stain Remains on PC

The White Stain is Partially Depolymerized Polycarbonate so FTIR shows thatit contains Absorptions for PC, Oligomers, and BPA Monomer

Polycarbonate

White Stain

Bisphenol A



The Surface of the Adhesive that was against the PC is encasedin a thin shattered PC Film that again contains Oligomers and BPA

Thin Shattered Film on Adhesive that was against the PC contains Polycarbonate, BPA, and Oligomers

Polycarbonate

BPA


The other side of the adhesive was against the Polyurethane and it is encased in that Polyurethane

Polyurethane Tube



What Chemical(s) Attackedthe Polycarbonate?

O

O

NO

OHO

OHO

DYMAX Disclosed 5 Components of this Adhesive

N,N-DimethylacrylamideIsobornyl Acrylate

Irgacure 184 Darocur 1173

Reactive Diluents

Photoinitiators

Ketone

Amide

These 4 are All Ketones and one is also an Amide. Ketones can Craze and CrackPolycarbonate and Amides can Depolymerize it to Bisphenol A. John Donohue -

[email protected]

Pre-UV Adhesive

Post-UV Adhesive

Adhesive Taken Off Device

Adhesive’s Spectrum Pre and Post Polymerization by UVDouble Bond at 1612 cm-1 Completely Consumed by Polymerization

Double Bond



Double Bond @ 1614 cm-1

N, N, Dimethylacrylamide’s Double Bond is Consumed during the PolymerizationThe Two Carbons Become Part of the Cured Adhesive’s “Backbone”

The Absorption Disappears as the Adhesive CuresThis Chemical Attacks the Polycarbonate


The Isobornyl Acrylate’s Double Bond is also Consumed by the Polymerization

Double Bond


Drug Eluting Coronary Stent Coatings

Part 10: Drug Eluting Heart Stent Coatings

John Donohue - [email protected] ©1996 American Heart Association

Edelman, E. R. et al. Circulation 1996;94:1199-1202

Angioplasty and Stenting are Competitive ProceduresDivergent processes of vascular repair after balloon angioplasty

and stenting of an atherosclerotic vessel


Divergent processes of vascular repair after balloon angioplasty and stenting of an atherosclerotic vessel. Balloon angioplasty (top) compresses and fractures the atherosclerotic plaque (light gray) and tunica media (black), slightly enlarging the artery. After a few days, a thin layer of platelet-rich thrombus (dark gray) lines the lumen and fills the dissection plane. The lumen shrinks from combined effects of early elastic recoil and later formation of a fibrocellular neointima (speckled area). Stent deployment after angioplasty (bottom) compresses the dissection plane and enlarges the lumen while stretching the artery with minimal elastic recoil. Within hours to days after stenting, caps of thrombus infiltrated with inflammatory cells (dark gray) form over stent struts (black rectangles), particularly abundant at sites of deep injury. Over ensuing weeks, a neointima forms (speckled area), thicker where injury is more severe. Although intimal growth after stenting is greater than after balloon angioplasty, the residual lumen is also larger, as the scaffolding of the stent maintains luminal dimensions. Late changes in arterial size are not depicted because the contribution of remodeling to restenosis after angioplasty or stenting remains incompletely characterized. (Figure prepared by James Squire.)

Edelman, E. R. et al. Circulation 1996;94:1199-1202


Stents scrape blood vessel walls. This injury causes reblockage.

Edelman and Squire


Stents scrape blood vessel walls

Edelman and Squire


Drug Eluting Coated Stent

3.0mm X 2.3mm


420μ X 550μ 300μ X 390μ



A Different Manufacturer’sDrug Eluting Coated Stent

3.0mm X 2.3mm

John Donohue - [email protected]μ X 550μ 300μ X 390μ

A Different Manufacturer’sDrug Eluting Coated Stent

IR Spectrum of PC 1036 from Biomaterials 21 (2000) 1847-1859

Phosphatidyl Choline (PC)coating, invented byBiocompatibles, Ltd., usedon some Medtronic andAbbott Drug ElutingCoronary Stents.

Spectra of coatings obtainedoff the actual stent surfacesshow the PC coating and theanti-restenosis drug it elutes.

All drug was extracted fromthe Abbott stent but PCcoating remains.



IR Spectra of pure PC, PC 1036, Medtronic Stent Coating, and Abbott Stent Coating

The Pure PC’s IR shows most of the vibrations present in the PC 1036 coating.

The PC 1036 IR was published back when Biocompatibles, Ltd. was trying to “drum up” big company interest in their materials. [This particular spectrum is slightly distorted (an “enlarged” 1090 vibration) because it is a surface spectrum (obtained via ATR) of a PC polymer in which the hydrophilic PC moieties have been rotated preferentially to the surface by contact with water. The 1090 is the C-O-P stretching vibration.]

The Medtronic (Endeavor™) and Abbott (BiodivYsio™) stent coating spectra were obtained by reflection off the stents’ surfaces.

The stent coatings are excellent matches to the spectrum of PC 1036. Since this is the coating Biocompatibles, Ltd. developed for the BiodivYsio stent, I believe it is the PC coating on the Medtronic and Abbott stents. EDAX can be run using the SEM to see if silicon is detected from the PC 1036 TSMA component. The literature published by Biocompatibles, Ltd. suggests a TSMA content of 3 to 5%. At this loading EDAX should detect the silicon.


Biocompatibles, Ltd. developed the PC-coatedBiodivYsio™ stent and marketed a number of PCpolymers. One of these polymers, PC1036, appearsto be the PC coating on the BiodivYsio stent,now a product of Abbott. It also appears to bethe coating Abbott has licensed to Medtronic forthe Endeavor stent.

PC 1036 is made using the four acrylic monomersshown here.>2-methacryloyloxyethyl phosphorylcholine (MPC)>lauryl methacrylate (LMA)>hydroxypropyl methacrylate (HPMA)>3-trimethoxysilylpropyl methacrylate (TSMA)

MPC supplies the PC functionality to the polymer.LMA helps the polymer adhere to metal surfaces.TSMA makes the polymer crosslinkable, whichimproves its adhesion and cohesion and helps control its rate of drug elution.HPMA is a co-crosslinker that, used with TSMA at 25% loading, gave good mechanical properties.AIBN (azoisobutyronitrile) initiates polymerization.

PC 1036 Biocompatibles, Ltd.

Biocompatibles, Ltd. paper


TSMA Hydrolysis initiates the Crosslinking of the Coating

The Drug Elution Rate is determined mainly by the extent of crosslinking.The hydroxy groups of the HPMA moiety will crosslink with TSMA also.

Biocompatibles, Ltd. paper


Part 11: Particulate Identification


Cardboard-Colored CelluloseOrganic Coating on one side


Biodegradation of an InsectThis insectdied ofnatural causesin the springof 2006.

(No insect’swere harmedin themaking ofthis document)

After storage in an airtight container for morethan one year, webbing is growing on it.

All 8.5mm X 11.2mm

Part 12: Fish Hooks, “Bait”, and Electronics


8.5mm X 11.2mm 2.3mm X 3.0mm

Webbing at Eye


Views of Webbing8.5mm X 11.2mm


… yields a better protein Spectrum after it is Squashed

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550u X 420u FOVsSpectra of Webbing on Aluminum Sheet …

Webbing placed on sheet

Webbing squashed on sheet


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Polyimide

White Epoxy

Green Ink

Blue Ink

8.5mm X 11.2mm

2.3mm X 3.0mm

Epoxy

Polyimide

Metal

Inkjet Cartridge Printhead

Laser Cut Metal “Window”


11.2mm X 8.5mm

3.0mm X 2.3mm

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PET + Butylacrylate Adhesive

Butylacrylate Glue

Cu & Glue is between PET & Polyimide

Ceramic beneath slotted Metal

Micaceous Cleavage of Ceramic

Printhead Dismantled – Piezoelectric Ceramic Under Metal


Who made the Chip that’s encased in hard black epoxy?

Original Photo Flipped Image

Toshiba


Fish Hook Manufacturing Processes:Cutting, Bending, Welding, Coating

8.5mm X 11.2mm FOVs


Fish Hook’s Point and Scratched Inorganic Coating:420u X 550u FOVs

infrared microscopy and microanalyses for hire: analytical lab for small companies

Technology

lower molecular

carrier gas

john donohue

hot autoclave

cobalt radiation

visible light

white stain

accelerated