Solve structures from microcrystalline particles when conventional single-crystal X-ray diffraction is delayed or impractical.
MicroED changes the bottleneck in small-molecule structure work. Conventional single-crystal X-ray diffraction still provides excellent crystallographic evidence when suitable crystals can be grown, but many pharmaceutical materials are available only as powders, micron-scale crystallites, mixed solids, trace impurity fractions, or samples that resist crystal-growth optimization.
The 2026 Triclinic workflow white paper positions MicroED as a direct route from sub-micron crystallites to molecular structure, reducing the dependency on growing large single crystals and moving structure determination from a crystal-growth problem into an analytical workflow.
MicroED is a structure-determination tool, not a black-box identification test. The diffraction experiment can define the molecular geometry and unit cell from very small crystals, but interpretation still depends on data quality, beam sensitivity, dynamical scattering, phase mixtures, atom assignment, hydrogen placement, and expert crystallographic judgment.
The strongest Triclinic examples pair MicroED with orthogonal evidence. PXRD connects single-particle results to the bulk powder. HRMS constrains formula and atom counts for impurity assignments. Raman, IR, NMR, DSC/TGA, microscopy, and chemistry knowledge help distinguish a defensible structure assignment from a plausible but under-supported model.
| Project question | MicroED contribution | Orthogonal evidence to include | Example source |
|---|---|---|---|
| Can a microcrystalline powder yield a definitive structure? | Collect diffraction from individual nano- to sub-micron crystallites instead of waiting for large single crystals. | PXRD for bulk phase match; SCXRD if suitable crystals later become available. | Q2 2026 MicroED workflow white paper. |
| Is an LC impurity structurally identified? | Provides a 3D crystal structure from a tiny crystalline residue or HPLC fraction deposited on a grid. | HRMS accurate mass, candidate formulae, isotope pattern, MS/MS, and chemistry review. | Q1 2026 MicroED + HRMS impurity white paper. |
| Is a multicomponent solid a salt or a cocrystal? | Determines the crystal structure and can support proton-position assessment when data quality is sufficient. | PXRD, SCXRD when available, Raman/IR/NMR, pKa context, and hydrogen-bonding analysis. | Q4 2024 NBA-PYR salt/cocrystal study. |
| Are multiple phases or low-level crystalline impurities present? | Targets individual crystallites so minority particles can be indexed and solved instead of being hidden in a bulk pattern. | PXRD, microscopy, spectroscopy, and targeted fractionation where needed. | 2024 Triclinic / ELDICO pharmaceutical case-study seminar materials. |
| Does an ASD or cloudy crystallization drop contain crystalline material? | Can analyze micro- and nanometer-sized crystallites when conventional visual inspection or bulk diffraction is inconclusive. | XRPD, VT/VRH-PXRD, DSC/TGA, DVS, microscopy, and formulation history. | MicroED capability sheet and 2024 summit agenda. |
The Q1 2026 Triclinic impurity white paper uses a model compound to show a real limitation of MicroED: electron diffraction can define the molecular framework, but atoms with similar scattering behavior may still be misassigned if the structure is interpreted in isolation. HRMS narrows the candidate molecular formulae and makes the final refinement chemically defensible.
The NBA-PYR study connects MicroED to a concrete CMC decision: salt versus cocrystal assignment. The study reported one salt and two cocrystal forms, confirmed structures using XRD and MicroED, and solved a new cocrystal polymorph from a single impurity particle.
These MicroED-specific examples show how the method supports structure elucidation, impurity identification, form classification, and low-sample-amount investigations.
Author: Shawn C. Comella, Gary C. George III, and Steef X.M. Boerrigter
Publication date: Q2 2026
Project relevance: Source for the XRD versus MicroED schematic, the SCXRD versus MicroED workflow comparison, and the positioning of MicroED as an early structure-elucidation tool when powders or sub-micron crystals are available.
DownloadAuthor: Gary C. George III, Jason Vanlerberghe, and Stephan X.M. Boerrigter
Publication date: Q1 2026
Project relevance: Source for the impurity example showing why HRMS is paired with MicroED when atom assignment or formula selection is ambiguous.
DownloadAuthor: Stephan X.M. Boerrigter, G. Patrick Stahly, Matthias Zeller, and Christian Jandl
Publication date: Q4 2024
Project relevance: Source for the salt/cocrystal example, the hydrogen-placement figure, and the XRD-versus-ED structural comparison.
DownloadSource: 2024 Triclinic Labs / ELDICO Scientific summit materials
Project relevance: Source for practical application examples: polymorph, salt, and cocrystal identification; absolute configuration; unknown impurities in formulations; and structure work from very low sample amounts.
Source: Triclinic MicroED capability document
Project relevance: Source for application examples involving 10-1000 nm crystallites, small solid quantities, supplier-material verification, low-level impurities, crystallization drops, metabolites, and amorphous-solid-dispersion crystallinity questions.
Related structure elucidation service or orthogonal method for projects that require defensible structural evidence.
View serviceRelated structure elucidation service or orthogonal method for projects that require defensible structural evidence.
View serviceRelated structure elucidation service or orthogonal method for projects that require defensible structural evidence.
View serviceRelated structure elucidation service or orthogonal method for projects that require defensible structural evidence.
View serviceRelated structure elucidation service or orthogonal method for projects that require defensible structural evidence.
View serviceThe first technique depends on the decision, material amount, sample form, and prior data. Single-crystal X-ray diffraction is preferred when suitable crystals are available; MicroED is valuable for microcrystalline particles; NMR supports connectivity and local environment; LC/MS HR/MS supports formula and fragment evidence; Raman/IR and microscopy help connect molecular and physical identity.
Yes, many structure-elucidation workflows can be scoped around limited material, but feasibility depends on crystallinity, purity, sample matrix, detection limit, and whether the question requires definitive structure, tentative identification, or triage.
Yes, if the work is scoped to the evidentiary standard required. Reports should state what the data prove, what remains ambiguous, and what additional evidence would change the conclusion.
No single method answers every structural question. Orthogonal evidence reduces misassignment risk by connecting formula, connectivity, phase identity, crystal structure, purity, sample history, and matrix behavior.
A suitable sample contains crystalline particles small enough for electron diffraction, remains sufficiently stable under the electron beam, and provides interpretable diffraction from one or more crystallites. Purity, disorder, preferred orientation, and mixed phases can affect feasibility.
Share the amount available, crystallinity, prior XRPD or microscopy evidence, suspected identity, urgency, and the structural decision the data must support.
