Labeling

In many laboratory information systems, electronic entry of a test order in the laboratory or at a nursing station for a uniquely identified patient generates a specimen label bearing a unique laboratory accession number. A record is established that remains incomplete until a result (or a set of results) is entered into the computer against the accession number. The unique label is affixed to the specimen collection container when the specimen is obtained. Proper alignment of the label on a specimen tube is critical for subsequent specimen processing when bar-coded labels are used. Arrival of the specimen in the laboratory is recorded by a manual or computerized log-in procedure. In other systems, the specimen is labeled at the patient’s bedside, and patient identification and collection information is provided; then the labeled specimen is submitted to the laboratory with a requisition form. There it is assigned an accession number as part of the log-in procedure, which is usually a computerized process.

After accessioning, specimens undergo the technical handling processes. For those processes requiring physical removal of serum or plasma from the original tube, secondary labels bearing essential information from the original label must be affixed to any secondary tubes created. Some automated analyzers sample directly from the original collection tube while simultaneously reading the accession number from the bar code label on the tube. Secondary bar code labels, if necessary, may be generated at the time of accessioning, or in some analyzers by a built-in printer that is activated when the analyzer is programmed.

Many methods are used to achieve secondary labeling when bar code labels are not available. A number may be handwritten on the specimen cup, or a coded label may be affixed to the original tube or to a specimen cup. The label numbers require correlation with a manual or computer-generated work or load list. The load list usually records accession numbers in sequence with the physical positions of cups or tubes in the loading zone of the analyzer. This loading zone may be (1) a revolving tray or turntable, (2) a mechanical belt, or (3) a rack or set of racks by which specimens are delivered in a predetermined order to the sample aspiration station of the analyzer.

In those analyzers that do not automatically link specimen identity and sample aspiration, the sequence of results produced must be linked manually with the sequence of entry of specimens. Some analyzers print out or transmit to a host computer each result or set of results from a specimen through the position of the specimen in the loading zone or the accession number programmed to that position.

Bar Coding

A major advance in the automation of specimen identification in the clinical laboratory is the incorporation of bar coding technology into analytical systems. A bar coding system consists of a bar code printer and a bar code reader, or scanner. One- and two-dimensional bar coding systems are available. A one-dimensional bar code is an array of rectangular bars and spaces arranged in a predetermined pattern according to unambiguous rules to represent elements of data referred to as characters. A bar code is transferred and affixed to an object by a bar code label that carries the bar code and, optionally, other noncoded readable information. Symbology is the term used to describe the rules specifying the way data are encoded into the bars and spaces. The width of the bars and spaces, as well as the number of each, is determined by a specification for that symbology. Different combinations of bars and spaces represent different characters. When a bar code scanner is passed over the bar code, the light beam from the scanner is absorbed by the dark bars and is not reflected; the beam is reflected by the light spaces. A photocell detector in the scanner receives the reflected light and converts that light into an electrical signal that then is digitized. A one-dimensional bar code is “vertically redundant” in that the same information is repeated vertically—the heights of the bars can be truncated without any loss of information. In practice, vertical redundancy allows a symbol with printing defects, such as spots or voids, to be read.

In practice, a bar code label (often generated by the laboratory information system and bearing the sample accession number) is placed onto the specimen container and is subsequently “read” by one or more bar code readers placed at key positions in the analytical sequence. The resultant identifying and ancillary information then is transferred to and processed by the system software. Initiating bar code identification at a patient’s bedside ensures greater integrity of the specimen’s identity in an analyzer. Systems to transfer information concerning a patient’s identity to blood tubes at the patient’s bedside have been introduced in many hospitals, and several companies are now offering these systems.

Unequivocal positive identification of each specimen is achieved in analyzers with bar code readers. Advantages of the use of bar code labels include the following:

Examples of types of bar codes that are used in chemistry analyzers are illustrated in Figure 19-1.

Identification Errors

Many opportunities arise for the mismatch of specimens and results. The risks begin at the bedside and are compounded with each processing step a specimen undergoes between collection from the patient and analysis by the instrument. The risks are particularly great when hand transcription is invoked for accessioning, labeling and relabeling, and creation of load lists. An incorrect accession number, one in which the digits are transposed, or a load list with transposed accession numbers may cause test results to be attributed to the wrong patient. An additional hazard exists when specimens must be inserted into certain positions in the loading zone defined by a load list. Human misreading of the specimen label or the loading list may cause misplacement of specimens, calibrators, or controls. Automatic reading of bar code labels reduces the error rate from 1 in 300 characters (for human entry) to about 1 in 1 million characters barring (1) minor imperfections in printed bar codes, (2) improper bar code scanner resolution, or (3) skewed orientation of bar code labels on containers, all of which can result in read errors.

Use of Whole Blood for Analysis

When whole blood is used in an assay system, specimen preparation time is essentially eliminated. Automated or semiautomated ion-selective electrodes, which measure ion activity in whole blood rather than ion concentration, have been incorporated into automated systems to provide certain test results within minutes of the drawing of a specimen. This approach now is used commonly for assays of electrolytes and some other common analytes. Another approach involves manual or automated application of whole blood to dry reagent films and visual or instrumental observation of a quantitative change (see Chapter 20).

Automation of Specimen Preparation

Several manufacturers have developed fully automated specimen preparation systems. (These systems will be described in later sections of this chapter.)

Pneumatic Tube Systems

Pneumatic tube systems provide rapid specimen transportation and are reliable when installed as point-to-point services. However, when switching mechanisms are introduced to allow carriers (the bullet-shaped containers used to hold specimens) to be sent to various locations, mechanical problems may occur and may cause misrouting of carriers. In addition, close attention to the design of the pneumatic tube system is necessary to prevent hemolysis of the specimen. Avoidance of sudden accelerations and decelerations and the use of proper packing material inside the carriers will minimize hemolysis.

Electric Track Vehicles

Electric track vehicles have a larger carrying capacity than pneumatic tube systems and do not have problems with damaging specimens by acceleration and/or deceleration forces. Some systems maintain the carrier in an upright position with the use of a gimbal (a device that permits a body to incline freely in any direction or suspends it so it will remain level when its support is tipped), enabling the carrier to move both vertically and horizontally on an installed electric track. The containers can hold dry ice or refrigerated gel packs with specimens if desired. They are especially useful in quickly transporting specimens between floors or between laboratory locations that are some distance from each other, by making use of the space in the ceiling plenum above the laboratory. A primary disadvantage is the cost of moving the track and loading/unloading stations if the laboratory is expanding or moving; in addition, the stations may be larger than the pneumatic tube stations. If the station is not located directly in the central laboratory (centralized testing; core laboratory), additional staff may be necessary to unload the carts and transport the specimens to their final destination, and the electric track system may not achieve its desired goal of rapid specimen transport.

Mobile Robots

Automated guided vehicles (AGVs), also called mobile robots, have been used successfully to transport laboratory specimens both within the laboratory and outside the central laboratory.¹³ They are easily adapted to carry various sizes and shapes of specimen containers and are reprogrammable with changes in laboratory geometry. In addition, in a busy laboratory setting, delivery of specimens to laboratory benches by a mobile robot can be more frequent than human pickup and has been shown to be cost-effective. Inexpensive models follow a line on the floor, whereas others have more sophisticated guidance systems. Their limitations include the need to batch specimens for greater efficiency and, in most cases, the requirement for laboratory personnel to place specimens onto or remove specimens from the mobile robot at each stopping place. Some mobile robots have been integrated with robotic systems that automate loading and unloading of specimens; others initiate an audible or visual signal of their arrival at a specified station so that employees are able to load or unload the specimens being transported. Box 19-3 lists several vendors that provide mobile robot systems for clinical laboratories.

Discrete Processing Systems

Positive–liquid displacement pipettes are used for sampling in most discrete automated systems in which specimens, calibrators, and controls are delivered by a single pipette to the next stage in the analytical process.

A positive-displacement pipette may be designed for one of two operational modes: (1) to dispense only aspirated sample into the reaction receptacle, or (2) to flush out sample together with diluent. Both systems use a plastic or glass syringe with a plunger, the tip of which usually is made of Teflon.

Pipettes may be categorized as (1) fixed-, (2) variable-, or (3) selectable-volume (see Chapter 9). Selectable-volume pipettes allow the selection of a limited number of predetermined volumes. Pipettes with unlimited or selectable volumes are used in systems that allow many different applications, whereas fixed-volume pipettes usually are used for samples and reagents in instruments dedicated to the performance of only a small variety of tests.

Carryover

Carryover is defined as the transfer of a quantity of analyte or reagent from one specimen reaction into a subsequent one. Because it erroneously affects analytical results from the subsequent reaction, carryover should be minimized or eliminated. In discrete systems with disposable reaction vessels and measuring cuvets, carryover is caused by the pipetting system. In instruments with reusable cuvets or flowcells, carryover may also arise from incomplete cleaning of the cuvettes or flowcells between assays.

Most manufacturers of discrete systems reduce sample-to-sample carryover by using disposable pipette tips or by incorporating wash stations for the sample probe that flush the internal and external surfaces of the probe with copious amounts of diluent. An adequate ratio of flush and rinse to specimen volume controls carryover in many cases to acceptable values. Appropriate choice of sample probe material, geometry, and surface conditions also influences carryover. Some systems wipe the outside of the sample probe to prevent transfer of a portion of the previous specimen into the next specimen cup. Use of disposable sample probe tips allows complete elimination of contamination of one sample by another inside the probe, as well as the carryover of one specimen into the specimen in the next cup, because a new pipette tip is used for each pipetting.

In practice, the reduction of sample-to-sample carryover is a more stringent requirement for automated analyzers that perform immunoassays in which some analytes (e.g., human chorionic gonadotropin) have a wide range of concentrations. Some systems use extra steps, such as additional washes, or an additional washing device to reduce carryover for selected tests to acceptable limits. Because extra steps reduce overall throughput, additional rinsing functions are initiated (by computer operator selection) only for assays with a large analytical measurement range.

Sample-to-sample carryover can be detected by the preparation of two sample pools—one having a very high analyte concentration (H), the other having a low concentration (L). By running sequences of tests such as HHHLLLHHLLHHLL, if sample-to-sample carryover is present, higher results will be noted in the low-concentration sample analyses that immediately follow a high-concentration sample analysis.

Reagent-to-reagent carryover also can occur on discrete systems that use a common reagent probe for pipetting all reagents; its minimization or elimination requires use of the same approaches just described for sample-to-sample carryover. Detection of reagent-to-reagent carryover can be difficult for end-users and usually requires the involvement of the instrument vendor. Users should be aware that the introduction of third party reagents in “open” channels on otherwise closed systems may introduce problems with reagent-to-reagent carryover. Consultation with the system manufacturer is advised to determine how to test for and minimize such carryover.

Reagent Identification

Labels on reagent containers include information such as (1) reagent identification, (2) volume of the contents or the number of tests for which the contents of the containers are to be used, (3) expiration date, and (4) lot number. Many reagent containers now carry bar codes that contain some or all of this information, and the manufacturer is able to retrieve any pertinent information when necessary.

Other advantages of using reagent bar codes include (1) facilitation of inventory management, (2) ability to insert reagent containers in random sequence, and (3) ability to automatically dispense a particular volume of liquid reagent. Furthermore, when a bar code reader is coupled with a level-sensing system on the reagent probe, it alerts the operator as to whether a sufficient quantity of reagent exists to complete a workload.

A bar code on a reagent container may also contain information about (multiple) calibrators, such as the definition of a calibration curve algorithm and values of curve constants defined at the time of reagent manufacture. Accompanying calibrator materials provided in their own bar code tubes at the time of manufacture ensure that calibration functions are integrated properly into the analysis.