Micro-Chemical Analysis for hire / Ending Recalls and Factory Shutdowns / FTIR Microscopy and expert analyses / Medical Device Problem-Solving, Failure Analysis, and Reverse Engineering

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
Flow
Direction

2. Hazy Translucent
Area on border of
Bubble
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 and
of the part’s shaving was Clear Translucent
Cross-section of Bubble
Clear translucent polymer slice

3. 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
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
“Zooming in” on Hazy deposit on Bubble’s circumference
Increases the Secondary Amide Absorbance Peaks relative to the PLG’S...
PLG
PLG
...therefore the hazy area is a Secondary Amide
FTIR Microscopy
Zooming in

4. -1.0
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Absorbance
1000150020002500300035004000
Wavenumbers (cm-1)
Three Amide deposits on Aluminum with PLG dissolved away.
Two Amide deposits squashed onto Aluminum.
Methylene Chloride removed
most of the PLG
Squashed onto Aluminum
Squashed onto Aluminum
Amide
Amide
... so what is this Secondary Amide and what is it doing?

5. Synergistic Use of
FTIR Microscope
and
Gas Chromatograph / Mass Spectrometer
The two most powerful instruments
In Analytical Chemistry
... so what is this Secondary Amide
and what did it do?

6. The SIS Thermal Desorber
A Heated Inlet for GC/MS
sold by Scientific Instrument Services

7. Carrier Gas Flowpath to Mass Spec Detector
Pure He flowing through
glass lined steel tube
that contains sample.
Tube is injected into
GC Inlet and heated.
Volatiles separate on
column and are analyzed
by the MS.

8. Excised tiny intact Bubbles melted in THDSB
pop and release CO2 (and NOT O2 or N2)
PLG Hydrolysis in heated tube releases Lactide and Glycolide

9. Hydrolysis of PLG: The Chemistry Occurring
The moisture in the amide flakes
forms steam during injection
molding, inflating the bubbles.
The steam is consumed as it
hydrolyzes the PLG, filling the
bubbles with CO2.
as per Dr. C. C. Chu of Cornell

10. Spectral changes of PLG hydrolyzed on Hotplate
Carbonyl and Hydroxyl orbitals
are formed as the controls
hydrolyze on the hotplate.

11. Spectral changes of PLG vs proximity to amide deposit
The concentration of the same Carbonyl
and Hydroxyl orbitals is seen to increase
with increasing proximity to the bubbles
formed by the amide flakes. This large
gradient in concentration occurs across
a microscopic range of distance from the
bubbles’ walls.
It is in analyses like this one that the
FTIR Microscope is the very best tool
there is. No other instrument could
do this work: easy and exact spatial
localization of a chemical identification.

12. 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

13. Ending $100MM/yr Device Factory Shutdown
caused 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.

14. 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 developed
to measure RAPIDLY the
Concentration of individual pellets
proving Bimodal Distribution
Most Pellets had
Right NaBZT amount