The Project: Create a device to enable the high speed digital scanning of slides for use in virtual microscopy.

The Solution: Use precision motion control components to ensure extremely high resolutions, that are free of imperfections, are achieved.

Pathologists today face multiple challenges in delivering timely high quality results. The advent of virtual microscopy, or the creation, management, and analysis of digital slides via a computer monitor, is fulfilling its recent promise to overcome many of those obstacles caused from the use of glass slides by providing a dramatically more efficient, faster, and objective environment for microscopic inspection. With the development of a unique, high-resolution, high-speed digital slide scanner, Aperio Technologies Inc. is leading the way with a system that utilizes a innovative line-scanning method to get the job done, enabling the digitization of pathology. This system is made possible with a unique motion control system and Heidenhain scales that are at the heart of this innovation.

The Aperio
ScanScope System
“These innovations begin with the understanding that the conventional method of capturing a glass slide digitally is with image tiling,” explained Greg Crandall, vice president of engineering for Aperio. “Image tiling is a well-known technique that involves the capture of multiple small regions of a microscope slide (in the form of thousands of tiles) using a traditional CCD camera. Line scanning, on the other hand, employs a linear-array detector, in conjunction with specialized motion control components, a microscope objective lens, and customized optics, to capture a small number of contiguous overlapping image stripes.” This patented linear-array system is the key to the fast and accurate ScanScope System. The specialized motion control components within each of these systems include three ultra-precise linear encoders from Heidenhain Corp. These scales are used to maintain extremely constant velocity during line scanning and are instrumental in ensuring uniform focus across the slide.

It is important to understand that line scanning is a significant advancement in rapid, high-resolution virtual microscopy. Unlike the stop-and-go nature of conventional image tiling, the linear-array scanning is performed in a continuous motion, making this ideally suited for rapid slide digitization. With tiling, for example, a single 15 x 15 mm glass slide may typically require approximately 3,000 image tiles to be captured and aligned at a scanning resolution of 0.5 µm/pixel (20x). This could take approximately one hour. In contrast, Aperio’s line-scanning method only needs to capture and align 15 image stripes. Aperio’s digital slides are produced in about three minutes and the image will be at a higher resolution and of superior quality to an image created via tiling. This is because Aperio’s digital slides are created at 24-bit color giga-pixel resolution using high numerical aperture objectives—the same as found on conventional optical microscopes. “With this system, the pathologist should never need to go back to that glass slide or look at it through a microscope, as this digital version will provide all the information necessary right on his or her computer,” explained Crandall.

A slide is scanned using the Aperio ScanScope System. A section of a Heidenhain encoder is also pictured.
The image quality is reliant upon uniform constant velocity; any changes in velocity would cause the image to appear smudged or could introduce artifacts. Aperio’s constant velocity is maintained point-to-point using small nanomotors and a 1.0 micron Lida 400 encoder on the Y-axis, and a 10th-micron encoder on the X-axis. “It was important that we coupled our motor with an extremely high resolution feedback loop encoder,” said Crandall, “and Heidenhain fit the bill.”

During this speed control loop, there has to be the same number of counts per unit of time to create the constant velocity. This is a key issue, especially in applications such as these where the speed control has to be as good as plus/minus one count per unit of time, and is the point at which an encoder is necessary.

With very small dimensions of its own, the Lida 400 encoders—with a grating pitch of 20 microns—are indicated for use anywhere precise positioning is required in a small package. With a scanning head of only 12 mm, it can be installed in very tight spaces, yet provide a large scanning area of 14.5 mm2. “We previously tried using other encoders,” said Crandall, “but about a year or so ago, discovered we got better performance and easier installation at less cost with the Heidenhains.”

Crandall also noted that another area where a Heidenhain encoder is applied to this system and is of critical importance is in the area of focus. On the Aperio system, optimal focus is achieved by another innovative method that makes adjustments on-the-fly to accommodate the subtle but significant topology changes inherent in tissue specimens. In order to do this, Aperio uses another nanomotor and another Lida 400 encoder (here at a 50 nanometer level) to focus the Z-axis to meet their requirements of 1/4 micron focusing accuracy. This system adjusts focus from one scan line to the next, approximately 1,000 times more frequently than image tiling systems. “This way, the digital slide created is perfectly focused everywhere and we are left with captured images that are free from optical aberration, have no tiling artifacts, and are practically seamless. This is very important in creating a digital slide that is of maximum use to a pathologist,” said Crandall.

Because of innovations seen in the ScanScope Scanner, high resolution virtual microscopy is beginning to make an impact. Over 100 of these ScanScope Scanners are now in the field with applications in clinical practice, as well as in research and education. The scanner, along with its advanced motion control systems, Heidenhain encoders, and software, is enabling anywhere/anytime viewing of digital slides in high throughput situations while automating tedious tasks, improving analysis and interpretation, and making telepathology practical today.
For additional information on the technologies and products discussed in this article, see the following websites: