Laboratory-scale X-ray characterization techniques have long been the foundation of materials analysis and industrial metrology. However, when analytical requirements extend to detecting crystalline phase contamination down to 0.01 wt%, probing local atomic ordering in highly disordered nanomaterials, or capturing sub-second chemical dynamics in complex environments, standard laboratory sources cannot deliver the brilliance or energy resolution required.
Synchrotron light sources, including 4th-generation facilities, are designed for exactly these measurements. By generating photon flux per unit area many orders of magnitude higher than conventional X-ray tubes, synchrotrons offer:
Energy tunability: Continuous photon energy selection across soft and hard X-ray regimes to target element-specific excitation edges and tune surface vs. bulk penetration depth.
High spatial resolution: Micro- and nano-focused beam spot sizes for spatial mapping of heterogeneous interfaces and 3D sub-micron internal structures.
Excellent signal-to-noise ratio and throughput: High-brilliance beams lower detection limits and reduce measurement times from hours to seconds.
Gaining access to synchrotron facilities has historically been difficult for industrial R&D and QA teams, as securing beamtime through standard academic pathways typically involves peer-reviewed proposal workflows and unpredictable waiting periods that rarely match industrial project schedules. Measurlabs solves this issue by providing commercial access to state-of-the-art synchrotron beamlines for clients worldwide, through one point of contact and with transparent turnaround times of 2–4 weeks.
This article summarizes several synchrotron-based analysis techniques and their advantages over laboratory-scale methods, drawing on practical experience from analysis projects Measurlabs has conducted for clients in the pharmaceutical, nanotechnology, and chemical industries.
Technique overview
Different synchrotron X-ray techniques yield different information on the chemical composition and nanoscale structure of substances, which means that it is often necessary to use several methods to characterize the sample comprehensively. Table 1 summarizes the information obtainable with synchrotron techniques offered by Measurlabs.
Table 1: Information obtained using selected synchrotron X-ray techniques
Technique | Obtained information |
Synchrotron X-ray diffraction (XRD) | Identification and quantification of crystalline phases and total amorphous content, identification of lattice parameters, crystallite size, and microstrain parameters. |
Synchrotron X-ray photoelectron spectroscopy (XPS, NAP-XPS) | Elemental composition and chemical binding states, observation of chemical changes in real time, in nearly ambient conditions (vs. conventional XPS, which requires a vacuum). Tunable photon energy to investigate samples with varying surface sensitivity. |
(Ultra) small-angle X-ray scattering (USAXS/SAXS) | Particle size, shape, and size distribution of nanoparticles in the range of ~0.1 nm to 6.3 µm with synchrotron USAXS or SAXS. |
Wide-angle X-ray scattering (WAXS) | Degree of crystallinity in partially ordered materials, interatomic spacings and unit cell d-spacings, orientation of fibers and crystals (e.g., in UHMW polymers) |
X-ray absorption near edge structure (XANES) | Oxidation states, coordination numbers, local coordination symmetry, and electronic structure. |
Extended X-ray absorption fine structure (EXAFS) | Interatomic distances, coordination numbers, and identity of neighboring atoms in the local atomic environment. |
Pair distribution function (PDF) | Total atomic pair correlations in crystalline, nanocrystalline, and amorphous materials, including phase confirmation and crystallite size determination for nanoparticles too small to be characterized reliably with XRD (<5–10 nm) |
Synchrotron computed tomography (CT) | Sub-micron voxel size on intact parts without destructive cutting; phase-contrast imaging of thin interfaces; imaging of samples directly through sealed/sterile packaging. |
The following examples illustrate how these techniques are applied in practice across different industries.
Example application 1: Comparative characterization of pharmaceutical products
Before bringing generic drugs to market, pharmaceutical manufacturers must show that they are equally safe and effective as the approved reference drug. In addition to conducting clinical bioequivalence studies, the process can require extensive comparative physicochemical characterization of the new and existing drug, especially when regulatory agencies consider the active pharmaceutical ingredient (API) or finished drug formulation to be complex.
This is the case, for example, with intravenous ferric carboxymaltose products, which require molecular-level characterization for approval by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).1 A combination of several synchrotron X-ray techniques (XANES, EXAFS, high-resolution powder XRD, PDF, and SAXS) can be used to collect the required information, including on iron species' oxidation states, iron core size and morphology, polymorphic form of the core, particle size distribution, and characteristics of the amorphous carbohydrate surface layer.
Example application 2: Substance identification and characterization for REACH registration of UVCB substances and nanoforms
The EU REACH Regulation requires manufacturers and importers of chemical substances to submit a registration dossier to the European Chemicals Agency (ECHA) with sufficient analytical data to establish the identity of the substance. This requirement is particularly challenging for UVCB substances – substances of unknown or variable composition, complex reaction products, or biological materials – because their full composition is inherently difficult to define.2 Synchrotron XRD is well suited to substance identification of inorganic UVCB substances, such as mixed ash, metallurgical slags, and cement clinker, as the high resolution enables detection of trace crystalline phases and therefore allows detailed documentation of crystalline constituents and their relative quantities in the REACH dossier.
To account for nano-specific properties and potential hazards, nanomaterials also require more extensive physicochemical characterization than conventional materials under REACH and other EU regulatory frameworks, including food and cosmetics legislation. Synchrotron methods can be used in the process to fulfill information requirements regarding characteristics such as crystal structure (XRD), particle size (SAXS), and redox potential (XANES and EXAFS).3 Amorphous or partially amorphous nanomaterials in particular tend to require more sensitive techniques and often a combination of several techniques to establish the nanoscale structure with enough certainty.4
Example application 3: Nanoscale structural analysis of polymers for R&D and failure analysis
Nanoscale structural properties, including fiber orientation and degree of crystallinity, can have a significant impact on the mechanical performance of engineering plastics such as ultra-high molecular weight polyethylene (UHMWPE), and they should therefore be analyzed during the R&D phase to optimize product performance. The same properties can also be investigated during failure analysis of polymeric coatings and nanocomposites, as identifying deviations from the expected structure in different batches or at different time points during or after manufacturing can help identify the causes of failure.
As polymeric materials often produce weak or diffuse X-ray scattering signals, they tend to require the higher beam intensity and resolution of synchrotron sources to resolve reliably. Synchrotron WAXS can be used to determine polymer fiber orientation and strain, while SAXS can resolve lamellar spacing and detect lamellar thickening, which can be a sign of thermal aging or annealing. Further insight into the chemical changes that occur on polymer and nanocomposite surfaces under specific, realistic environmental conditions can be obtained using synchrotron XPS, which allows the observation of such changes in near-ambient conditions.
Example application 4: In situ surface failure analysis of micro-electronic coatings under controlled atmospheres
Functional microcomponents, such as microsensors, passivated semiconductors, and oxide encapsulation layers, often experience unexplained performance degradation during operation under specific atmospheric conditions. Identifying the root cause of such failures typically requires analyzing chemical state changes at the extreme sample surface (top 1–3 nm). However, conventional laboratory-scale XPS requires ultra-high vacuum (UHV), preventing direct observation of how the material interacts with surrounding gases in real-world operational environments.
Synchrotron near-ambient pressure XPS (NAP-XPS) overcomes this limitation by enabling core-level photoelectron spectroscopy at mbar-range gas pressures. In failure analysis studies, components exposed to different environmental conditions, such as noble versus ambient gas atmospheres at varying temperatures, can be analyzed in situ within controlled gaseous environments to isolate the exact chemical drivers of performance loss.
Example application 5: Non-destructive 3D micro-structural inspection of optoelectronic and semiconductor micro-assemblies
Precision micro-assemblies, such as integrated photonic devices, semiconductor packages, and micro-optical sensors, rely on sub-micron alignment and thin organic adhesive bonding (1–2 µm) across fused silica, silicon, and metallic layers. Inspecting internal layer continuity and interface integrity with laboratory X-ray CT is limited by geometric magnification, which restricts sample diameter to sub-millimeter scales and requires destructive sectioning of intact components. Additionally, laboratory absorption CT provides minimal attenuation contrast between low-Z organic adhesives and surrounding silica or silicon matrices.
Synchrotron micro-CT (SR-µCT) resolves these limitations using parallel-beam optics and high photon flux. Region-of-interest (ROI) local tomography achieves isotropic voxel sizes down to ~0.4 µm inside intact 10 mm assemblies without destructive cutting. Propagation phase-contrast imaging (PPCI) exploits X-ray wave refraction to enhance edge contrast at material boundaries, resolving 1–2 µm adhesive layers and interface delaminations. High beam brilliance also allows non-destructive 3D scanning directly through sealed, cleanroom-compatible packaging to prevent sample contamination.
Our synchrotron analysis services
Measurlabs provides access to a broad range of synchrotron-based analysis techniques for pharmaceutical, nanotechnology, and chemical characterization, regulatory substance identification, and materials R&D. Examples of popular services include:
Ferric carboxymaltose characterization by synchrotron X-ray methods (XANES, EXAFS, HR-XRD, PDF, and SAXS)
Synchrotron XRD for UVCB substance identification (crystalline phase identification and quantification)
PDF analysis to determine the local atomic structure in amorphous or nano-structured materials
Near-ambient-pressure synchrotron XPS for in situ surface chemistry analysis of polymers and nanocomposites
Synchrotron SAXS and WAXS for nanoscale structural analysis of polymers and nanoparticles
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References:
1 See FDA Draft Guidance on Ferric Carboxymaltose and EMA Reflection paper on the data requirements for intravenous iron-based nano-colloidal products developed with reference to an innovator medicinal product
2 The information requirements are set out in Annex VI to Regulation (EC) No 1907/2006 on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), and more information is available in ECHA guidance for identification and naming of substances under REACH and CLP.
3 See Table 2 in the Scientific Committee on Consumer Safety (SCCS) guidance on the safety assessment of nanomaterials in cosmetics and Table B.1 in the European Food Safety Authority (EFSA) guidance on risk assessment of nanomaterials to be applied in the food and feed chain: human and animal health for more information on the characteristics to be determined and the suggested analysis methods.
4 Section 3.1.2.2. in the ECHA appendix for nanoforms to the guidance on registration and the guidance on substance identification suggests a combination of XRD and X-ray absorption spectroscopy (i.e., XANES and EXAFS) as one possibility for characterizing amorphous or partially amorphous nanoforms.