The food manufacturing and pharmaceutical industries produce products taken directly into human bodies, so they must provide high levels of safety and quality.
To meet these requirements, appropriate quality control and quality assurance need to be performed by scrutinising crystals precisely in each process, such as the acceptance of crystallised raw materials, the crystallisation process, and the observation and analysis of processed crystals.
This section introduces application examples of our 4K digital microscope, which supports difficult and time-consuming observations and analyses of crystals with a single unit.

Efficiency Improvement of Observation and Analysis of Crystals (Amino Acids, Proteins, and Other Substances)

What Is a Crystal?

A crystal is a form of solid substance in which constituents—such as atoms, molecules, or ions—are arranged sterically in regularly repeating patterns, forming a space lattice. The arrangement of atoms in a crystal is called a crystal structure and the minimum unit in a regularly repeating pattern is called a unit cell. In addition to atoms and inorganic molecules, even proteins having more than one million molecules can crystallise.
A typical crystal is a polyhedron, consisting of many flat planes and sharp edges that form various angles. Many crystals are anisotropic, so they have different properties—such as refractive index and elasticity—in different directions.

Needs for Crystals and Problems in Observation and Analysis

In the food manufacturing and pharmaceutical industries, crystal technologies are widely used for various active pharmaceutical ingredients (API) and substances—such as proteins, amino acids, and starch—used in the product manufacturing process. Because using crystals can add further value to the products, an increasing number of manufacturers use the crystallisation process or procure crystals from the outside. In product manufacturing using crystals, the degree of purity, shape, particle size distribution, solubility, flow characteristics, and some other factors are important in maintaining or improving quality.
Many characteristics of crystals come from the atoms or molecules that constitute the crystal or from the relative positions of the atoms or molecules in the crystal. These characteristics appear anisotropically especially in the optical properties such as the refractive index, absorption coefficient, angle of optical rotation, and depolarisation ratio. On the other hand, typical evaluations of procured crystals or crystallisation results mainly use the observation and analysis of the appearance, shape, particle size distribution, and other similar items of crystals as typical parameters.
However, observation and analysis of these items are difficult because crystals are extremely small and have complex three-dimensional shapes as well as different degrees of light transparency, light refraction, and diffuse reflection. The following are some specific problems.

  • Because crystals have three-dimensional shapes, only a part of the sample can be brought into focus in high-magnification observations.
  • The edges have various angles that generate diffuse reflections, making it difficult to determine lighting conditions.
  • Many crystals have low contrast with the background, which makes it difficult to capture the outlines of crystals.
  • Quantitative analysis and evaluation are difficult due to the above factors.

Read on for an introduction to application examples of our 4K digital microscope, which improves the sophistication, quantification, and work efficiency of crystal observation and analysis by solving various problems.

Application Examples of Our 4K Digital Microscope, Which Solves the Problems in Crystal Observation and Analysis

To solve problems in observation and analysis of challenging targets such as crystals, KEYENCE has applied feedback from on-site operators in these fields to manufacture new digital microscopes that meet their needs for over 30 years.
Our latest result is the VHX Series 4K digital microscope. This product has an observation system that allows operators to enjoy its high performance and various functions with simple operations, eliminating the overspecialisation of work and improving work efficiency.
Read on for an introduction to application examples of the VHX Series in crystal observation and analysis.

API crystal observation, analysis, and report creation

Because API crystals, used in the making of drugs, have three-dimensional shapes, images cannot be focused throughout the entire field of view in many observations. Additionally, crystal-specific transparency and light refraction lower the contrast, making it difficult to observe the shapes clearly.

The VHX Series 4K digital microscope supports various lighting conditions with a single unit, enabling quick and easy condition determination, which takes a lot of time. This microscope is equipped with the Multi-lighting function, which automatically captures multiple images with omnidirectional lighting at the press of a button. Crystal observation can be started promptly using high-resolution 4K images by simply selecting an image suitable for the purpose from the captured images.
Because the data of multiple captured images is stored, any image can be easily used to observe the target again, for example, on a later day under different lighting conditions.
Additionally, by simply selecting a past image, the conditions used for capturing that image can be reproduced. A different sample of the same type of target can be easily observed under the same conditions on a different day and time by a different operator.

Observation of API crystals using the VHX Series 4K digital microscope
Ring illumination (100x)
Transmitted polarising illumination (100x)

The VHX Series can also seamlessly switch from observation to analysis of crystal grain sizes. The automatic area measurement/count function can be used to perform binarisation on an area specified with simple operations at an arbitrary threshold. Area measurement and counting of crystals can be automatically performed.
This function automatically measures, calculates, and counts detailed values—such as the number, average area, standard deviation, maximum value, minimum value, area ratio, and other items of crystals in the selected area as well as the area, perimeter, maximum diameter, and minimum diameter of each crystal—and then displays these values in a list. In the selected area, targets that are not required can be excluded and overlapping targets can be separated, which enables highly accurate analysis.

Analysis of API crystals using the VHX Series 4K digital microscope
Ring illumination (100x) + Automatic area measurement/count
Ring illumination (100x) + Automatic area measurement/count

Additionally, Excel can be installed directly on the VHX Series, enabling captured images and values to be output and laid out in an arbitrary template, creating a report automatically.

These various functions improve the simplicity and efficiency of the series of tasks required for observation, analysis, and report creation, significantly reducing the man-hours.

Starch crystal observation with high contrast

Starch crystals have high transparency and, consequently, low contrast on the background. This makes it difficult to observe the crystal outlines and shapes clearly.

In addition to the backlight that provides transmitted lighting, the VHX Series 4K digital microscope is equipped with the High Dynamic Range (HDR) function, which captures multiple images at varying shutter speeds and composes into an image with high colour gradation. With this function, high-resolution 4K images can be captured with high contrast even for targets—like starch crystals—having low contrast on the background, enabling clear observation of crystal outlines and textures.

Starch observation using the VHX Series 4K digital microscope
Transmitted illumination (1000x)
Transmitted illumination + HDR (1000x)

Observation of amino acid and protein crystals

The VHX Series 4K digital microscope, which combines high resolution with a large depth of field, is equipped with a versatile lighting unit having high functionality. This unit provides various lighting conditions such as transmitted illumination (backlighting), coaxial illumination, and polarising illumination.
Additionally, the Multi-lighting function, which automatically captures multiple images with omnidirectional lighting, quickly prepares the lighting conditions suitable for each crystal.
The VHX Series’ high performance, functionality, and observation system enable easy observation with high-resolution 4K images even for crystals having varying appearances, such as those of amino acids and proteins, whose observation conditions are difficult to determine.

Observation of amino acid crystals using the VHX Series 4K digital microscope
Transmitted polarising illumination (500x)
Transmitted polarising illumination (500x)
Observation of protein crystals using the VHX Series 4K digital microscope
Transmitted illumination (50x)
Transmitted illumination (50x)

A 4K Digital Microscope That Improves the Efficiency of Observation and Analysis of Crystals and Work Involved in the Food Manufacturing and Pharmaceutical Industries

It is difficult to determine conditions for and analyse crystals, and their observation and analysis take a lot of time and effort. As the examples introduced above show, the VHX Series 4K digital microscope greatly improves the efficiency of this observation and analysis.

Thanks to the combination of an optical system and a 4K CMOS image sensor that enables the capturing of high-resolution 4K images, a versatile lighting system that supports the transparency of crystals, and an observation system that makes various functions accessible with simple operations, crystal observation can be reasonably sophisticated.

This microscope seamlessly supports the automatic area measurement and counting of crystals in the observation field of view and the automatic creation of reports with a single unit, greatly improving work efficiency.
Equipped with many other functions, the VHX Series provides powerful support for various observation and analysis tasks in the food manufacturing and pharmaceutical industries.

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