S PECIMEN H ANDLING S YSTEMS

Initially, the only automated solutions for labs involved TLA, in which sample handling and transport systems were configured to automate the preanalytical, analytical and post-

analytical phases of sample processing. Medical technicians could load sample tubes into a TLA system, program the system, and the system would perform the multiple duties that otherwise would have to be done by lab personnel.

Then modular automation appeared on the market, in which different, separate automated components of the sample handling process had be configured to meet a lab's specific needs, even if those needs might change over time. Typical front-end modules can track, centrifuge, decap, inspect, aliquot, label, recap, or sort sample tubes in preparation for testing on a variety of analyzers that can be either part of the integrated system or standalone equipment. These modules are connected by transport systems and operated by software that can be controlled from a PC, and easily interfaced with a LIMS.

Labs will use modules by a single manufacturer for specimen handling applications, since a manufacturer’s modules might not necessarily interface with another manufacturer's modules. However, as common standards are adopted, labs should be able to mix and match modules from different manufacturers. Despite advances in laboratory automation, many sample handling tasks remain a manual process in the under-automated clinical laboratory.

The laboratory unit operation is the basis of laboratory architecture. It can include sample transport, sample processing, and data handling. In the early 1980s, robotic- centric models of laboratory automation transported samples and performed many unit operations. They were not very efficient. The work station model, which performed an automated function involving a limited group of operations, was efficient but limited. Now the robot-centric model is in the past, and the integrated system model, a collection of devices that perform an automated process involving a large number of operations by using multiple work stations serviced by a general-purpose handling system, is moving into the laboratory.

A normal sample handling system can be comprised of various types of handling units, including a centrifuge, cap opener, aliquoter, bar code labeler, cap restopper, sorter, analyzer units, a built-in rack conveyer provided in each handling unit, and a transportation line which connects these handling units. The handling unit and another handling unit, the transportation line and the handling unit, or a transportation line and another transportation line are connected in series.

Sample handling can be performed by an automated centrifuge unit that separates blood samples into serum and cells; a cap opener unit which automatically removes caps

from sample containers; an aliquoter that aliquotes serum from mother sample containers to daughter sample containers; a bar code labeler which labels a bar code label with the same sample ID as the mother sample on the daughter sample container; a restopper unit that restops the sample containers with a cap; a sample sorting unit that sorts the sample containers into groups for testing; and a chemical analyzer which automatically performs a chemical analysis of samples.

Many sample handling systems on the market can be tied into a transportation line for transporting a rack holding samples. They can include a rack loading device that supplies the sample rack to the transportation line; a rack storage device for storing the sample rack transported by the transportation line; and several handling units disposed along the transportation line for applying a treatment on the samples. Also part of the specimen handling system can be a reader that reads identification information of the sample rack being transported; and a central controller which monitors the operational status of each handling unit and determines when and where sample racks are to be moved, based on identification information at the inoperative handling unit.

Other specimen handling systems can be based overhead, requiring virtually no floor space and only a minimal amount of bench space. They incorporate state-of-the-art conveyors suspended near the ceiling that transport, log-in and sort blood specimens in standard specimen containers. Specimens placed into the system at bench-level bins are automatically singulated and loaded onto cleated conveyors and lifted to the main conveyor belt near the ceiling. The barcoded labels are then read as the containers are rotated under an optical scanner. The specimens are then diverted to the appropriate branch conveyor and lowered back to the bench level by cleated conveyors. This type of specimen handling system is rapid and accurate, requires no special containers, allows laboratorians to move unimpeded below it, and is inexpensive by automation standards.

The market for specimen handling systems used in clinical laboratories is expected to grow as automated systems continue to move into these labs. The market’s growth is seen in Table 4-11.

Table 4-11

World Market for Clinical Lab Specimen Handling Systems 2008-2012

Revenues (in billions)

2008 2009 2010 2011 2012

$0.50 $0.53 $0.57 $0.63 $0.69

Source: Kalorama Information

LIMS

Clinical laboratory automation has evolved from an idea rootedin the mechanical aspects

of specimen manipulation in the early1970s to a more complex information systems-

driven technology today. Today, a laboratory information management system (LIMS)

involves software that is used in the laboratory for to manage and direct samples, laboratory users, instruments and other laboratory functions, such as invoicing, plate management and work flow automation.

The task of managing laboratory data is not a new one. Over the past two decades, the use of LIMS has revolutionized how laboratories manage their data. A LIMS is more than software. It is the workhorse of the laboratory that encompasses work flow combined with user input, data collection, instrument integration, data analysis, user notification, and delivery of information and reporting. The idea behind an LIMS is to create a seamless organization in which instrumentation is integrated in the lab network. Equipment can receive instructions and work lists from the LIMS and return finished results, including raw data, back to a central repository where the LIMS can update relevant information to external systems. Lab personnel will perform calculations, documentation and review results using online information from connected instruments, reference databases and other resources using electronic lab notebooks connected to the LIMS. Management can supervise the lab process, react to bottlenecks in work flow and ensure regulatory demands. External participants can place work requests and follow up on progress, review results and print out analysis certificates and other documentation.

There are several important interdependencies between software andhardware. If

the software functionality is absent, the hardware cannot be expected to perform.

actuate that hardware function. To allow random access, one must havea single tube per

carrier design so that each specimen has individualreal-time access to any work cell or

device. To allow for reflex testing, there must be real-time control of hardware and

instruments by the software that manages the overall operation. To allow routing, there

must be more than one transportation path to move a specimen to one or many

instruments.

Several software systems now include functionality for boththe procedure and the

process. At the procedural level, rulescan be applied that allow only the performance of

specific testson an identified matrix, such as only to perform a complete blood count on

EDTA-treatedor heparinized whole blood. The rules processing aspect of the software

component of an automation system should be able to: monitor quality using theprocess

control system; monitor results; monitor the instrument and its operation; implement

repeat testing decisions; implement reflex testing; canceltests; and manage the workload

of the entire operation based on the need for turnaround time, throughput, instrument

utilization and instrument uptime.

The ability to interface between the LIMS and the overall automation system has

been enhancedby the implementation of Health Level 7 system-to-system interfaces.The

National Committee on Clinical Laboratory Standards (NCCLS) issued a proposed

standard (AUTO 3P) that specifies theHealth Level 7 interface as the system-to-system

communications methodologyfor connecting a LIMS and the lab automation system.

Clinical laboratory automation technology derives its usefulness from

functionality -- functions that are performedor supported by technology. Functionality is

heavily dependent on the approach that is applied to develop automation technology.

There are several automation design issues that are of importance, including the

philosophy of automation systems design, the implementation of process control

software, the relationship betweenhardware and software, user interfaces to the system,

the interface with LIMS, and the interface between the automation system and other

hardware components.

Process control software used in today’s laboratory requires several important

componentsand functionalities, including:

A basis in moderninformation technology, which requires hardware and operating

systemsthat are vertically upgradable.

Transportation system management at both the local device and overall system

Specimencontainer tracking so that any specimen can be identified inits physical location on or in the automation system.

The ability to initiate repeat testing so that a specimen that may yield a certain

result canbe rerouted using the rules embedded in software to repeatthe test on another

instrument using a different methodology orto confirm the test on the same or another

instrument.

Reflextesting in which an additional test can be performed at the samework cell-

work station, or a specimen can be trafficked onto another instrument for subsequent

testing that is the result ofapplying a rule against the result of the first test.

Information systems integration so that LIMS and other informationcomponents

of analyzers can be combined to makea functional automated laboratory. In this instance,

the instrument can be managed using rules and other software-driven parameters,

essentially replacing the technologist at the individual instrument.

For example,the system software would "know" through the information passed

by LIMS that the patient with a high urea valueis from the dialysis unit and that the test

does not need tobe repeated. A rule can provide the functionality necessaryto make the

determination.

LabVantage, Bridgewater, NJ, ThermoFischer Scientific and LabWare are among the many companies that offer a variety of LIMS products. The market for LIMS in clinical laboratories is expected to grow as software management plays a greater role in controlling processes and work flow, as automation systems incorporate even more complex technology. The market’s growth is seen in Table 4-12.

Table 4-12

World Market for Clinical LIMS 2008-2012

Revenues (in billions)

2008 2009 2010 2011 2012

$0.40 $0.43 $0.47 $0.51 $0.56