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 Part 4: Nailing the Answer and Preventing a Recall Flow Direction
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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
1534 1648
3060
3288
0.2 0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
2.6
2.8
3.0
3.2
3.4
Abs
orba
nce
1000 1500 2000 2500 3000 3500 4000 Wavenumbers (cm-1)
“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
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Abs
orba
nce
1000 1500 2000 2500 3000 3500 4000 Wavenumbers (cm-1)
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 Cornell
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
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