Cell analyzer demands precise movement

In mankind's ongoing battle with cancer, as with any battle, the first imperative is to "know thine enemy". But with cancer, the primary challenge is to ‘see' the enemy. Cancer research and treatment efforts hinge on identification at the cell level. Immunicon Corporation,Huntingdon Valley, PA, has been developing and commercializing diagnostic and research products for rare cell analysis and molecular research, with an initial focus on cancer.

In June, 2006, Immunicon won a Silver Medical Design Excellence Award for its CellTracks Analyzer II. The Analyzer II is a fluorescence microscope used to count and characterize fluorescently labeled cells that are immunomagnetically selected and aligned. It is used with the CellTracks AutoPrep System and with specific reagent kits. Unlike its predecessor, the CellSpotter Analyzer, the CellTracks Analyzer II is automated.

The importance of the CellTracks Analyzer II is better understood as part of a complete process. Malignant carcinomas are derived from epithelial cells that are not normally found in circulation. Cancer metastasis occurs when cells shed from the primary tumor, enter the circulation and begin to grow in distant locations of the body. The scientific challenge is to develop a method to capture very small numbers of these circulating tumor cells (CTC) from a background of billions of cells in a tube of blood. Immunicon uses a ‘systems' approach. In fact, their CellSave Preservative Tube was developed to preserve the fragile CTCs during their trip to the lab site. In the lab, the CellTracks AutoPrep System standardizes and automates sample preparation. To further optimizing recovery of CTCs, reagents were developed for the CellSearch System. The CellTracks Analyzer II is then used to count and characterize CTCs. These reagents are marketed by Veridex, LLC, a Johnson & Johnson company.

To understand the challenge that the engineers faced, it's important to visualize the CellTracks Analyzer II's stages. Frank Modica, manager of mechanical engineering for Immunicon, was responsible for the overall mechanical design of the Analyzer II.

"There are four stages that we use. Two of them position the sample. The third one is the focus stage that positions the objectives, so that the images are in focus. The fourth one moves the proper filters in place, which produces the imaging in the three colors," explains Modica. Principal manufacturing engineer Art Marlin depicts their automated movement as working in concert with one another to take multicolored images of the cellular sample that is in the chamber.

The decision to use piezo electric motor technology in conjunction with linear bearings enabled the Analyzer II to behave like a microscope stage under computer control. "We wanted to be able to tell the stage where to go within micron resolution," Marlin says.

The selected linear bearings needed to meet specific requirements in order to achieve perfect positioning. The bearings would be determined by the amount of space within the product envelope, distance to be traveled, load to be carried and most critical of all, the degree of accuracy required. The instrument's envelope dictated miniature bearings be chosen for their reduced height.

For a medical application, the instrument has a large stage at 300 mm., but it is not high-load. However, the alignment and accuracy of the stage was strategic. A cross roller type linear bearing provides the most accurate form of linear motion. "The cross roller bearing is in the X coordinate, which was necessary to keep the X and Y stationery; any movement between frames could distort the images. In addition, there are two 375mm. slide guide bearings that are in the long (Y axis) length," says Marlin.

The cross roller bearing selected is designed and built by NB Corporation. It is the SV type slide way that consists of two R type roller cages, which have precision rollers in a cross arrangement and four rails that have V-shaped raceway surfaces. Rollers provide a larger contact area than ball bearings, reducing elastic deformation, which results in consistently precise movement. Since the rollers do not recirculate, they all carry the load. This produces greater rigidity, as well as high-load capacity. Another benefit of using rollers that do not recirculate is that there is less frictional resistance fluctuation. In fact, there is little or no difference between static and dynamic frictional resistances — even under low-load conditions — making them well suited for minute motion. Furthermore, being completely stainless steel makes them ideal for clean room applications.

According to Marlin, taking an overlay of three images in three different colors was necessary. If those images are not registered one on top of the other, it's impossible to get an idea of what the cell looks like. The instrument is connected to a PC so the images are seen on a typical flat screen PC monitor. The system magnifies the cell at 10X, but depending on the screen resolution, it can be seen as far larger.

For the three remaining axes, Immunicon chose NB's SEB type slide guide, which consists of a block and a guide rail, both of which have two precision ground raceway grooves. The two-raceway and four-point contact structure of the SEB types minimize their height, making them well-suited to installations with limited space. Being relatively wide, the SEBs provide greater moment load, more than the project actually required. More importantly, the SEB's standard radial clearance is twice as accurate as conventional slide guides. The economical nonretained- ball version provides friction- free short travel distances in both single and double widths — both of which are used in the Analyzer.

"We had a very rapid development cycle for this project," explains Modica. "Being able to go through a few design iterations and having the material was important. The quality had to be there, but the delivery was key in getting this done in the time allotted. One of the major competitors wanted six to eight weeks to get product from Japan. NB was able to deliver in three weeks. The NB bearings had the performance we needed, plus the price was very attractive. And yes, cost was a factor."

There are five NB bearings used, one in each of the first three stages and two in the fourth stage. And, while Modica gives credit to NB for being, "very responsive," Marlin adds that NB helped Immunicon achieve getting the prototype components through their office within a short period of time, helping to expedite evaluation of system components. "The bearings performed smoothly and were able to give us the necessary cell resolution in the detail that we need for analysis," adds Marlin.

For additional information visit the NB Corporation of America website (www.nbcorporation. com).