Vol. 11 •Issue 6 • Page 107
Specimen Transport: Steps to Standardization
Labeling and sample recognition.
Clinical laboratory automation has been evolving over the past 30 years as a means of improving laboratory performance. Analytical equipment has been successfully automated, yielding dramatic improvements in throughput, precision, convenience and data handling.
Automated analyzers now form the backbone of all clinical laboratories, both large and small. Over the past decade, automation has been extended to pre-analytical processes as well, but has been most often viewed as the large, fully integrated total laboratory automation systems.
Total laboratory automation developed first in Japan and other Pacific rim countries and began to appear in the United States more than 10 years ago. The automated systems began to address the wider array of laboratory processes, including pre-analytical functions such as sorting, centrifugation and specimen routing.
This evolutionary process has yielded laboratory instruments, support equipment and automation systems designed to meet the competitive pressures of the market place; however, these products were designed without attempts to make them compatible with each other. The designs and functionalities of these systems have been primarily proprietary, with little consideration for the incorporation of the competitors’ technologies.
Selection and use of specimen containers, vacuum blood collection containers and the carriers that transport them has also been a stumbling block in laboratory automation. Manufacturers have very successfully solved a myriad of problems arising in specimen collection and transportation. We have, for example, vacuum blood collection containers that can be opened without producing aerosols, developed to address the risks associated with HIV and other viral diseases. We have highly specialized vacuum blood collection containers for coagulation testing and tubes small enough to use for pediatric sampling. We also have a plethora of transport and storage containers that can protect both the handler and the specimen’s integrity in air transport and under a variety of conditions. Numerous manufacturers have succeeded in designing and producing containers for virtually any application.
However, all but a few of these containers were designed from the human user’s perspective. Until very recently, little attention was paid to the ability to handle containers in automated equipment or on automated transport lines.
As part of the larger effort to develop overall standards for the laboratory automation systems, the NCCLS attempted to develop standards for specimen collection and handling containers and for the single-container and multiple-container specimen carriers that transport them on and within automated laboratory instruments and systems.1,2
Efforts were made to develop a minimum number of container configurations, so automation and/or instrument designers, manufacturers and vendors could limit the scope of the specimen handling issues. Many containers on the market were used to help define these specifications. Originally, the specifications for the containers included a very narrow range of sizes. However, after comments from manufacturers, the specifications were modified to accommodate a larger array of individual specimen and sample containers or related products.
These wider specifications included an array of containers currently manufactured and used around the world. The specifications for container sizes allow for overlapping dimensions between the different nominal tube lengths and diameters. This overlap may preclude, in some instances, auto-detection of a closure on a container and might require that the number of containers used on or within a specific automation system be restricted by the vendor of the technology.
In addition to the standards developed for containers, standards were developed for transport carriers as well. There are two philosophical and design approaches to the transportation of specimen carriers: Some manufacturers developed carriers for single containers, while others preferred carriers for multiple containers-(or racks). The single-container-per-specimen carrier initially appeared to be the favored approach of laboratory automation vendors, while the multiple containers-per-specimen carrier appears to be favored by in vitro diagnostics (IVD) vendors for their instruments. Currently, both approaches can be found on the large-scale automated platform.
In designing these standards, the committees endeavored to preclude the creation of any standard that would inhibit the innovation and creativity of instrument and automation technology designers and avoid endorsement of a specific product.
The rationale for the single container-per-carrier is simple and easy to understand; it allows for more rapid distribution of each individual specimen to locations on an automated system. The rationale for the multiple containers-per-carrier was based primarily on the work of the Japanese Committee for Clinical Laboratory Standards.
Development of standards for specimen containers and transport carriers might foster further development of successful automated specimen handling. These container standards established dimensions for specimen collection containers, so use and processing of the specimen can be optimized by laboratory automation systems. The carrier standards set attributes for both single container and multiple container carriers to also facilitate optimized, automated specimen handling.
Many other kinds of containers are utilized in laboratory practice, including urine collection bottles or blood culture bottles. These containers are not usually placed directly onto laboratory transport systems, and are, therefore, outside the scope of this effort. Specimens (such as those used for drug abuse testing) collected in larger containers may be transferred to smaller containers for use on the laboratory automation system.
Container Standards
Specifications for containers used for automated laboratory applications, either as primary collection containers or as secondary containers prepared by automated systems, were established for four containers. Nominal sizes were set at 13 x 75 mm, 13 x 100 mm, 16 x 75 mm and 16 x 100 mm.
However, the specifications allowed for significant overlap in the heights, diameters and other parameters of tube design. This overlap may preclude, in some instances, auto-detection of a closure on a container and might require that the number of containers used on or within a specific automation system be restricted by the vendor of the technology. This latter situation is typical. For example, the automation system in the author’s laboratory permits the use of containers either 75 mm or 100 mm high but diameter is restricted to a very tight tolerance and only one cap design is permitted.
The standards allow that container body material may be either glass or plastic to maintain compatibility with collection and other processing of specimens for clinical laboratory testing. Use of glass tubes, however, is not permitted on many automation systems and glass is not considered as safe as plastic for handling, sorting and centrifugation.
The standards allow for the four types of closures most often used throughout the world. Again, assumptions were made that automation system devices, such as decapping or aliquotting components, that do not require decapping (direct sampling systems with closure-piercing capabilities) may force selection of only one of the closure configurations.
The configurations that fell within the standards were plug closures, film seal closures, plug closures with an integrated outer guard and screw-cap closures. Use of the different closure types vary geographically. Plug closures with an integrated outer guard is favored in North America while the screw cap closures are favored in many European countries.
Carrier Standards
Carriers capable of handling single and multiple containers are used in automation systems. Single carrier containers, often referred to as “pucks” because of their flat, circular design, have the advantage of easy rotation to orient tubes and labels. Other designs allow for transport of many containers and even microscope slides.
The standards specified that this carrier be able to:
•carry all four tube dimensions interchangeably,
•self center the container and
•allow reading of bar codes.
While several single tube carriers are in use, few can meet the requirement to handle multiple tube diameters simultaneously, so laboratories are again required to standardize what they handle to take advantage of this technology.
Current multiple tube carriers handle a widely varied number of containers. The largest currently are 10 place carriers or racks. The most widely used worldwide is probably the five position rack designed for the Hitachi analyzers and used by other vendors for container handling.
The standard for the multiple tube carrier allow it to carry as few as two tubes and does not actually specify a fixed number of containers, although it is based on the Japanese standard that does specify that it hold five containers.
The standard requires that the carrier be able to handle all four tube sizes and have a pitch (distance between carrier centers) of 22 mm and that the carrier be 22 mm wide. Like the single carrier, it must allow direct reading of bar codes from at least one side and be self-centering.
Other considerations such as barcode label placement were addressed as well and a specification for label placement was also developed by the NCCLS committees. This standard forced the bar code to the center of the tube and allowed ample space above and below the label to allow both positioning in a carrier and the overhang of vacuum blood collection cap shields.
Label placement is often a critical function in laboratory systems. While it would be favorable to allow placement anywhere on the container (human friendly approach), the instrument requires more precise placement to guarantee flawless reading of barcode labels. The actual dimensions of the labels also become critical in automated applications. Labels that extend too far below or above the center of a tube can interfere with the carrier’s ability to hold it properly or interfere with removal or rotation by automated handling devices.
Conclusion
The standards that have been developed and the process that was used to formulate them can provide a useful guide for the laboratory seeking to standardize its operations and sample handling routines even if they are not fully automated. While these standards are not likely to be adopted fully for some time, laboratories may want to consider internal standardization, beyond what they do now, to minimize costs, improve safety and enhance reliability of labeling and sample recognition.
Some of the standard specifications such as self-centering of tubes within carriers are already typical, but other parts of the standards have been criticized as too broad to facilitate automation development. Requirements that are narrower than the standards are already the norm in most automated laboratory platforms. However, vendors have not lost sight of this challenge and automation capable of sorting or even sampling from almost any kind of container or cap are on the horizon.
Dr. Orsulak is professor of Psychiatry and Pathology at the University of Texas Southwestern Medical Center and director of Toxicology at the North Texas Veterans Affairs Medical Center, Dallas. He has been involved in laboratory automation implemention, design and development for nearly 10 years.
References
1. Laboratory Automation: Specimen Container/Specimen Carrier; Approved Standard. NCCLS document Auto 1A. NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898 USA, 2000.
2. Bar Codes for Specimen Container Identification: Approved Standard. NCCLS document Auto 1A. NCCLS, 940 West Valley Road, Suite 1400, Wayne, PA 19087-1898 USA, 2000.
Warming Up to Room Temperature Transport Devices
With the advent of widespread screening for sexually transmitted diseases (STDs) and the onset of genomics and proteomics, molecular technologies will continue to proliferate. These technologies require a more convenient and standardized method of collection, transport and storage of the specimen so that the target nucleic acids and proteins are not degraded prior to testing. Refrigeration or freezing of the specimen is the normal practice; however, room temperature transport devices for handling urine, swab and blood samples are also an option.
Both urine and blood are very complex matrices that can rapidly degrade target nucleic acids and proteins required for molecular amplification assays. Nucleic acid and protein degradation occurs due to a few key factors:
•endogenous and exogenous enzymatic action on the target and
•changes in pH due to log phase growth, death and lysis of contaminating bacteria.
Additionally, some genotypes are more heat-sensitive (and can degrade faster) than others, so it is imperative that all genotypes be protected during transport and storage.
Some manufacturers have developed transport devices that eliminate the need to refrigerate urine or swab specimens used across a wide range of diagnostic assays. Chemistries have been shown to preserve all types of Chlamydia trachomatis genotypes in urine, even when exposed to 37ºC for several days. Room temperature, blood-based transport devices for whole blood, serum and plasma are under development.
Refrigerated urine transport can be a challenge, compounded by the increase in urine-based testing due to the inclusion of more male STD screening. Besides addressing the issues associated with thermostability of the nucleic acids and proteins, promising preliminary data suggests that some of these formulations also reduce the incidence of inhibition, therefore decreasing the incidence of false negatives.
Rob Koch is president, Sierra Diagnostics LLC, Palo Alto, CA.
