Triclinic Labs is capable of performing all types of optical, SEM, TEM, NIR, FT-IR, RAMAN microscopy and chemical imaging and mapping using state-of-the-art instruments and techniques.
Whether you require simple analysis for identification, contamination analysis of drug product or substance, more extensive interpretation of analytical data or development of analytical methods, we have the experience and techniques to meet your needs.
Instrumentation:
Technique |
Brand |
Model |
Notes |
Atomic Force Microscopy |
Digital |
|
All modes |
FT-IR |
Thermo |
Nicolet 6700 |
ATR, diffuse reflectance, transmission, gas cell, spectral libraries |
Hot Stage Optical Microscopy |
Linkam |
LTS420 |
Ambient – 600 °C |
Microtome |
Leitz |
Rotary |
Tungsten-Carbide, stainless steel, and Diamond Blades |
Microtome |
MTX |
Ultramicrotome |
Tungsten-Carbide and Diamond Blades |
Optical Microscopy |
Leica |
M80 - Stereo |
Still and dynamic image capturing |
Optical Microscopy |
Leica |
DM2500P - Compound |
Still and dynamic image capturing |
RAMAN |
Renishaw Dispersive |
inVia |
Chemical imaging, microsampling, Confocal, 785 nm laser |
RAMAN |
Thermo FT |
Module |
Micro and macro sampling, 1064 nm laser, spectral libraries |
Scanning Electron Microscopy & CryoSEM |
FEI |
NOVA nanoSEM FE |
High resolution imaging, cryo capabilities, environmental SEM |
SEM/Electron Dispersive X-Ray |
As above |
SDD |
Micro-elemental analysis, mapping |
Scanning Electron Microscopy Imaging and Analysis
Scanning Electron Microscopy (SEM) presents the opportunity to analyze samples for both morphological characterization and composition. Use of high-resolution field emission SEM can give detailed information on particle size, crystal shape and packing and overall structural characterization. SEM data is extremely helpful in identifying causes for manufacturing inconsistencies or in solving quality control issues.
CryoSEM involves freezing hydrated samples at temperatures as low as -130oC. and then examining their structure using SEM while they are frozen. This is the only way to fully evaluate a bulk, hydrated system without withdrawing any of the bound water. This powerful imaging technique allows sublimation of unbound water from the freshly fractured face of the frozen sample, revealing the basic underlying structure. Ideal samples are hydrogels, hydrated coatings and microbeads, tissue replacement products, and polymers that would normally deform under the electron beam.
When performing SEM, primary beam electrons interact with sample atoms to produce X-rays that carry information as to the type of atoms, and thus elements, in the sample. Electron dispersive x-ray analysis (EDX) utilizes this production of X-rays to identify types and locations of elements within the sample area. Such information can be displayed as a simple spectrum identifying the elements present, as elemental maps or line scans across the sample surface, or as a compositional determination of weight percentage or atomic percentage of the elements present based on their mass. We utilize a field emission SEM and associated EDX system, with a highly sensitive silicon drift detector (SDD), to identify impurities and unknown contaminants within samples and verify sample composition (Fig 1).
Figure 1. EDX analysis of Silvadene Cream (Silver Sulfadiazine) confirms the manufacture’s claim of 1% silver. Sulfur (S) has an atomic mass of 32.065 compared to that of a silver (Ag) atom at 107.86. With only one atom of each in the molecular formula for this compound, the ratios, based on weight% determined by EDX analysis, is correct within a reasonable margin of error.
Chemical Imaging & Mapping
The nature of the solids in formulated drug products, both the API and excipients, affects product performance. The analysis of such complex mixtures can be challenging, often requiring specialized techniques like spectral mapping and imaging.
Chemical imaging is a relatively new technique that requires sophisticated instrumentation. Triclinic offers Raman-based chemical imaging services. We also have experience utilizing image data obtained from near infrared devices and time of flight secondary ion mass spectrometric (TOF-SIMS) measurements.
Chemical imaging involves collection of an array of spectra covering a two-dimensional area. The data can be processed to give visual images showing the location of individual chemical species within the sampled area, or to measure physical features of mixture components such as particle size. Particularly useful has been the application of the techniques to solving problems associated with structured drug products like layered tablets or microspheres. Also, evaluation of mapping and imaging data can provide statistical measures of features like homogeneity or proximity of different chemical species.
(Fig 2.).
New uses for chemical imaging are emerging with high frequency. Triclinic's Dr. David Bugay is an expert in the area and can bring the most up-to-date application theories to bear on a wide variety of problems.
Figure 2. Raman Chemical Image: a tablet (upper optical microscopy image) containing an API was prepared according to procedures developed at Triclinic Labs to provide a planar surface for optical microscopy analysis and subsequent chemical imaging. The red/yellow/green/blue pixels indicated a gradient of high to low API concentration, respectively, across the sample tablet. Chemical imaging is useful for determining spatial distributions of API and excipients, domain size analysis, identifying different polymorphs in a drug product, identifying counterfeit drug products, and demonstrating infringement in a competitive product.
NIR, FT-IR
Infrared spectroscopy is a simple and reliable technique widely used in both organic and inorganic chemistry, in research and industry. It is used in quality control, dynamic measurement, and monitoring applications. As with all spectroscopic techniques, it can be used to identify and study chemicals. Triclinic utilizes two powerful Thermo units to perform contaminant identification, materials analysis and counterfeit analysis. The techniques are also useful for intellectual property support (patent prosecution and litigation).