Microcrystal electron diffraction (MicroED) can determine structures from crystals far too small for conventional X-ray diffraction, including some experiments that begin with sub-milligram quantities of material. It is not, however, a universal low-mass test. The sample must still form ordered three-dimensional crystals with suitable thickness, hydration, and diffraction quality. A cryo-transmission electron microscope (cryo-TEM), appropriate detector, grid-preparation workflow, and experienced operators are normally required for protein work.
What MicroED does for very small samples
MicroED is a diffraction method performed in a transmission electron microscope. Instead of exposing a large crystal to an X-ray beam, the instrument directs an electron beam through a tiny three-dimensional crystal and records the resulting diffraction pattern. By collecting diffraction while the crystal is rotated, researchers obtain data that can be used to determine an atomic structure.
As an Amazon Associate I earn from qualifying purchases.
The method is most useful when a target crystallizes, but the crystals are too small for routine single-crystal X-ray diffraction. It has been applied to proteins, peptides, and small molecules. The critical distinction is that MicroED reduces the crystal-size requirement; it does not remove the need for crystallization. A material that remains amorphous, produces only poorly ordered precipitate, or forms crystals with unsuitable thickness may still be a poor MicroED candidate.
Quick wins for a faster PC:
Scan for outdated or missing drivers - takes under a minuteDriver Scan →Repair Windows errors before they cause bigger problemsFix Now →Fix the driver behind crashes, sound loss and screen glitchesFind Drivers →Electron scattering is much stronger than X-ray scattering. That gives electrons high sensitivity to small crystals, but it also makes thickness a central constraint. A crystal can be too thick for clean, interpretable diffraction even when its face-to-face dimensions look attractive. Operators therefore look for ordered, sufficiently thin crystals that are separated from grid bars and neighboring crystals.
#1 Best Overall
- Read Before You Buy — No Video Output: These adapters support charging and USB 2.0 data transfer, but cannot transmit video signals. Except for standard USB webcams (which use USB data only), they are not compatible with HDMI/DisplayPort cables, video-capable USB-C hubs, or docking stations with video output.
- Convert USB-A Ports to USB-C: Designed to connect USB-C earphones, cables, flash drives, card readers, and other USB-C accessories to standard USB-A ports. Plug-and-play with no drivers or software required.
- Aluminum Alloy Housing: Built with a sturdy aluminum alloy shell that aids in heat dissipation and protects against daily wear and scratches. Designed to maintain a stable and secure connection.
- Compact & Travel-Friendly: The ultra-compact design allows the adapter to stay plugged into your device without blocking adjacent ports or adding bulk, reducing wear and tear on your original USB ports.
- 12-Month Warranty: Backed by a 12-month manufacturer warranty for peace of mind. Designed to meet strict quality control standards for reliable everyday performance.
How little material is actually needed?
There is no universal minimum mass for MicroED. The amount of starting material needed depends on how efficiently it crystallizes, how many usable crystals are produced, the crystal’s dimensions and thickness, diffraction quality, and how much material is lost during preparation and screening.
Thermo Fisher Scientific describes a MicroED structure obtained from approximately 10-12 grams of sample. That figure is an illustrative published example, not a guaranteed threshold for a new protein or small molecule. It should be read as evidence that extremely small quantities can be sufficient under favorable conditions, not as a promise that every sub-milligram sample will work.
The same vendor states that crystals only 100 nm in size can be analyzed. This is a reported capability example rather than a universal lower or upper cutoff. Crystal shape, thickness, order, composition, microscope settings, and detector performance all affect whether a particular 100 nm crystal produces useful data.
What’s actually slowing this PC down?
Pick the symptom - the matching free tool is one click away.
Rank #2
- 5-in-1 USB-C Hub: Experience comprehensive connectivity featuring a Power Delivery input, two USB-A 2.0 ports, a USB-A 3.0 port, and an HDMI port. (Note: The USB-C power delivery input port is only for connecting an external wall charger to power your laptop and cannot power peripheral devices.)
- 90W Pass-Through Charging: Achieve optimal charging with 90W pass-through power to your laptop, supported by a total input of 100W, with the hub reserving 10W for operational efficiency. (Note: Wall charger not included.)
- Quick Data Transfers: Accelerate your productivity with rapid data transfers using a high-speed 5Gbps USB 3.0 port and two 480Mbps USB 2.0 ports.
- 4K HDMI Display: Enhance your visual experience with a hub capable of delivering 4K resolution at 30Hz in both mirror and extend modes. Please note that this hub is compatible with MacBook (macOS 12 and newer), Windows 10 and 11, ChromeOS, and laptops equipped with DP Alt Mode and Power Delivery. Note: This device is not compatible with Linux.
- What You Get: Anker USB-C Hub (5-in-1, 4K HDMI), welcome guide, 18-month warranty, and our friendly customer service.
Consequently, “sub-milligram” answers only one part of the feasibility question. Before committing a precious sample, establish whether it forms crystals and whether a facility can inspect those crystals for diffraction.
Questions that matter more than the mass label
- Does the material produce three-dimensional crystals rather than amorphous powder or precipitate?
- Are the crystals sufficiently ordered to generate discrete diffraction spots?
- Are they thin enough to limit multiple scattering and other electron-specific problems?
- Can the crystals survive the intended preparation, including blotting, freezing, drying, or transfer?
- Is enough of the suspension available to load grids, screen multiple areas, and collect a complete data set?
- Can the facility collect enough angular coverage and process the resulting data?
Protein MicroED: the usual cryo workflow
Protein crystals are generally kept hydrated. A published protein MicroED protocol uses a sequence that preserves the crystals while making them compatible with a cryo-TEM.
- Prepare a crystal suspension. Start with protein microcrystals in their mother liquor or another solution that maintains crystallinity. Avoid conditions that allow the crystals to dry before vitrification.
- Prepare carbon-coated grids. Holey-carbon or continuous-carbon electron-microscopy grids are used in the documented protocol. Grid mesh, coating, support film, and surface treatment should be confirmed with the facility because these choices affect crystal distribution and background.
- Apply the suspension. Place a small amount of the crystal suspension on the grid. The goal is to distribute individual crystals across usable areas rather than create thick aggregates.
- Blot away excess liquid. Blotting leaves a thin film around the crystals. Excess liquid can prevent suitable vitrification, while excessive blotting can damage or dehydrate macromolecular crystals.
- Plunge-freeze the grid. Rapid freezing preserves the aqueous environment as vitreous ice. Macromolecular crystals should not be allowed to dehydrate because dehydration can damage crystallinity and diffraction.
- Screen in a cryo-TEM. Operators inspect grid squares and holes, locate crystals, and assess whether they are isolated, intact, and suitable for diffraction. Crystals separated from grid bars and from neighboring crystals are easier to center and collect from.
- Test diffraction. A selected crystal is exposed to the electron beam to determine whether it produces spots of usable resolution and intensity. Screening helps distinguish ordered crystals from material that only appears crystalline in imaging.
- Collect continuous-rotation data. The crystal is rotated while a high-speed detector records diffraction frames. The accessible rotation range and crystal stability influence how complete the data set can be.
- Process and solve the structure. Diffraction images must be indexed, integrated, scaled, and assessed for completeness before structure determination and refinement. Missing angular data can make processing and solving substantially harder.
This workflow explains why a cryo-TEM alone is not enough. Successful protein MicroED combines grid preparation, vitrification, low-dose imaging and diffraction, precision rotation, detector operation, and crystallographic data processing.
Rank #3
- Sleek 7-in-1 USB-C Hub: Features an HDMI port, two USB-A 3.0 ports, and a USB-C data port, each providing 5Gbps transfer speeds. It also includes a USB-C PD input port for charging up to 100W and dual SD and TF card slots, all in a compact design.
- Flawless 4K@60Hz Video with HDMI: Delivers exceptional clarity and smoothness with its 4K@60Hz HDMI port, making it ideal for high-definition presentations and entertainment. (Note: Only the HDMI port supports video projection; the USB-C port is for data transfer only.)
- Double Up on Efficiency: The two USB-A 3.0 ports and a USB-C port support a fast 5Gbps data rate, significantly boosting your transfer speeds and improving productivity.
- Fast and Reliable 85W Charging: Offers high-capacity, speedy charging for laptops up to 85W, so you spend less time tethered to an outlet and more time being productive.
- What You Get: Anker USB-C Hub (7-in-1), welcome guide, 18-month warranty, and our friendly customer service.
Small molecules use a different preparation logic
Small-molecule crystals can sometimes be dried or examined at room temperature, depending on the compound’s stability and the facility’s protocol. The International Union of Crystallography’s MicroED standards describe both liquid-suspended preparations and dry powders containing submicron crystals.
That flexibility does not apply automatically to proteins. Dehydrating a macromolecular sample can damage its lattice and reduce or eliminate useful diffraction. For a small molecule, drying may be acceptable; for a protein, maintaining hydration and vitrifying the grid is usually central. The correct route depends on the target’s chemistry, solvent sensitivity, crystal habit, and the instrument configuration.
MicroED compared with other diffraction choices
| Decision axis | MicroED | Conventional single-crystal X-ray diffraction | Serial X-ray diffraction |
|---|---|---|---|
| Crystal size | Designed for very small three-dimensional crystals, including reported 100 nm examples. | Usually requires a crystal large enough to intercept and diffract the X-ray beam effectively. | Can use many small crystals delivered serially; the number required depends on the collection setup. |
| Thickness constraint | Strong electron scattering makes crystal thickness a primary practical limit. | Crystal dimensions and X-ray absorption are important, but electron multiple-scattering constraints do not apply. | Each delivered crystal must provide adequate diffraction; size and exposure strategy vary by experiment. |
| Material quantity | An example structure used approximately 10-12 grams, but no universal mass threshold exists. | Often needs enough material to grow a comparatively larger single crystal. | May require many crystals, depending on delivery and redundancy requirements. |
| Macromolecular sample state | Typically hydrated and vitrified on an EM grid. | Usually mounted in a loop or other X-ray sample holder, with cryoprotection when required. | Crystals may be delivered in a stream, fixed target, or other serial arrangement. |
| Infrastructure | Cryo-TEM, grid preparation, plunge freezing for proteins, a high-speed detector, and specialist collection and processing expertise. | X-ray source, goniometer, detector, crystal mounting, and crystallographic processing. | Serial delivery hardware, an X-ray source and detector, and workflows for combining data from many crystals. |
| Completeness risk | Limited rotation, beam damage, crystal movement, or missing angles can make processing and structure solution difficult. | Rotation geometry and crystal lifetime determine completeness. | Completeness depends on the number and orientations of crystals successfully measured. |
No method is universally best. MicroED is compelling when crystals are too small for conventional X-ray work but remain ordered and thin enough for electrons. If a target yields a robust, larger crystal, conventional X-ray diffraction may be simpler. If many small crystals are available and an appropriate X-ray delivery system exists, serial X-ray diffraction may be an alternative.
Rank #4
- Dual Converters, Infinite Potential：Includes 2× USB C male to USB A female adapters and 2× USB A male to USB C female adapters. Perfect for a wide range of uses—tablets with Bluetooth keyboards, expand USB ports on macbook, and more. Two different converters for all your daily needs
- Next-Level 10Gbps & 3A Charging: No more slow 480Mbps, this usb to usb c adapter has a transfer speed of up to 10Gbps, allowing you to do more transferring in less time. This usb adapter fits both USB A and USB C charger, supporting up to 3A fast charging
- Upgraded Exquisite Craftsmanship: With an aluminum alloy housing and metal connector, the usbc to usb adapter is extremely durable and sturdy. Rigorously tested to withstand more than 10,000 times of plugging and unplugging, ensuring long-lasting performance
- Broad Compatible: The usb c to usb adapter widely supports all USB C/ USB A devices like laptops, tablets, cellphones, car chargers, and phone chargers. Such as compatible with MacBook Pro/Air 2023/2022, Thunderbolt 4/3 Devices,Apple MagSafe Watch 9/8/7/SE/Ultra, iPad Pro 2022/2021, Samsung Galaxy S23/S20/S10, and iPhone 17/16/15 Pro. Plug and play
- Please Note: To reach 10Gbps speed, keep the cable under 3.3 ft. For USB A Male to USB C adapters, try flipping the USB C connector. USB C Male to USB A adapters support bidirectional 10Gbps transfer within 3.3 ft
Practical sample-preparation checklist
Before making grids
- Record the crystallization condition, crystal habit, approximate dimensions, and whether crystals remain suspended or settle rapidly.
- Ask the facility whether it prefers holey-carbon or continuous-carbon grids and which mesh and coating are compatible with its holder.
- Confirm whether the sample will be handled as a hydrated suspension, a vitrified protein preparation, or a dried small-molecule powder.
- Agree on how much suspension or powder is needed for screening, repeat grids, and data collection.
During screening
- Prioritize isolated, well-defined crystals away from grid bars and aggregates.
- Check both imaging quality and diffraction; an object that looks crystalline may not be sufficiently ordered.
- Monitor beam exposure and crystal stability, since a crystal that diffracts initially may deteriorate during collection.
- Track crystal orientation and accessible rotation so that missing wedges or incomplete angular coverage are identified early.
Before structure determination
- Inspect diffraction resolution, spot separation, intensity, and consistency across rotation frames.
- Assess completeness and redundancy rather than relying on a few attractive images.
- Keep preparation history with the data: hydration state, freezing or drying route, grid type, and screening observations can explain later processing problems.
Common failure modes and what they mean
The sample does not diffract
Possible causes include poor crystal order, amorphous material mistaken for crystals, radiation damage, unsuitable thickness, or preparation damage. Re-examine crystallization and test a different crystal population or preparation condition before concluding that the target is impossible.
Diffraction is dominated by background or multiple scattering
Excess thickness is a likely concern because electrons interact strongly with matter. Aggregated crystals, thick ice, or a crystal lying across a support feature can also complicate the pattern. Better dispersion, thinner crystals, cleaner grid areas, or a revised loading and blotting procedure may help.
Protein crystals lose diffraction after preparation
Dehydration is a major risk for macromolecular samples. Keep the crystals in a compatible solution, minimize handling time, and validate blotting and vitrification conditions with the facility. A protocol that works for a dry small molecule should not be transferred directly to a protein.
Best Value
- 5-in-1 Connectivity: Equipped with a 4K HDMI port, a 5 Gbps USB-C data port, two 5 Gbps USB-A ports, and a USB C 100W PD-IN port. Note: The USB C 100W PD-IN port supports only charging and does not support data transfer devices such as headphones or speakers.
- Powerful Pass-Through Charging: Supports up to 85W pass-through charging so you can power up your laptop while you use the hub. Note: Pass-through charging requires a charger (not included). Note: To achieve full power for iPad, we recommend using a 45W wall charger.
- Transfer Files in Seconds: Move files to and from your laptop at speeds of up to 5 Gbps via the USB-C and USB-A data ports. Note: The USB C 5Gbps Data port does not support video output.
- HD Display: Connect to the HDMI port to stream or mirror content to an external monitor in resolutions of up to 4K@30Hz. Note: The USB-C ports do not support video output.
- What You Get: Anker 332 USB-C Hub (5-in-1), welcome guide, our worry-free 18-month warranty, and friendly customer service.
The data set cannot be indexed or solved
Incomplete angular coverage, inconsistent crystal orientation, overloaded images, weak spots, or movement during rotation can all impair processing. The IUCr standards specifically caution that incomplete angular data can make processing and structure determination substantially harder. Collecting from a better-isolated crystal or combining properly measured crystals may be necessary.
Accessing a service instead of building the workflow
A service facility can be the most practical route when an organization does not have a cryo-TEM, plunge freezer, high-speed detector, or MicroED-trained staff. The University of Pennsylvania Electron Microscopy Resource Lab publishes a hands-off MicroED service for small-molecule crystals and protein microcrystals.
| Published service detail | What it means for planning |
|---|---|
| Recommended crystal size: 50–200 nm | Use this as that facility’s guidance, not as a universal MicroED size range. |
| Submission: one protein sample or four small-molecule samples | Package samples within the facility’s stated submission limits and confirm current requirements before shipping. |
| Billing: instrument time and consumables billed separately | Request a current estimate that separates microscope usage from grids, preparation materials, and other consumables. |
Service terms, fees, scheduling, and sample acceptance criteria can change. Verify them directly before allocating scarce material. Ask whether the service includes crystallization advice, grid preparation, screening images, data collection, data processing, or only selected parts of the workflow.
Recommended Free Tools
What to ask a facility before sending a precious sample
- Does the facility routinely handle this target class—protein, peptide, or small molecule?
- What crystal dimensions and thicknesses does it prefer, and how should those dimensions be measured?
- Should the sample arrive as a liquid suspension, vitrified grid, or dry powder?
- Which carbon-coated grid type, mesh, and support film should be used?
- How much material is required for an initial screen and for repeat attempts?
- What diffraction detector, rotation method, and data-processing pipeline are available?
- Will the facility report only diffraction images, or will it provide processed data and structure-solving support?
- How are instrument time, consumables, shipping, and unsuccessful screening attempts charged?
Bottom line for a sub-milligram project
MicroED is a credible way to determine a crystal structure when the available material is below a milligram and the crystals are too small for conventional X-ray diffraction. The decisive requirement is not a particular mass; it is the combination of crystallinity, order, suitable thickness, survivable preparation, usable diffraction, and access to the right cryo-EM expertise. Treat published values such as approximately 10-12 grams, 100 nm crystals, or a facility’s 50–200 nm recommendation as context-specific examples. A preliminary conversation with a MicroED service or core facility can prevent the most expensive mistake: spending a scarce sample on a preparation that the target or instrument cannot support.
Quick Recap
Product prices and availability are accurate as of the date/time indicated and are subject to change. Any price and availability information displayed on Amazon at the time of purchase will apply.
