Purpose

The universal goal to reduce errors in laboratory testing appears successful with advances in barcode sample identification and laboratory automations. However, at children’s hospitals, a majority of the samples arrive in the lab in microtainers, where the standard barcoding and automation solutions do not apply.

With this in mind, the CHILDx (pronounced Child Diagnostics) Advisory Board invited a variety of industry representatives to a mini-symposium to address these concerns. CHILDx is an initiative co-sponsored by the University of Utah, Department of Pathology, the Primary Children’s Medical Center, and the University’s ARUP Laboratories. Panelists were asked to give short presentations explaining their organizations’ philosophy and design approach on the 

• design of pediatric sample collection containers 
• design of instrumentation with minimum sample volume
• adaptation of pediatric sample containers to automated platforms
• specimen identification solutions for pediatric samples

It is understood that no single vendor has an encompassing solution, and that vendors need to work together, and with pediatric health care providers, to meet the needs of pediatric patients.

Dr. Ron Weiss served as moderator.

 

Introduction

Dr. Phil R. Bach, Clinical Chemist at Primary Children’s Hospital, Salt Lake City, Utah, opened the meeting with a presentation on the challenges he sees in his institution. The flow charts show the ideal path a sample follows in an automated laboratory (see charts on the following page).

A phlebotomist receives the requisition, obtains the 5-7 mL tubes for the draw and goes to the bedside. Barcode labels, which correspond to the patient’s wristband, are placed on each tube. Once drawn, the labeled samples go to the laboratory and follow an automated pathway in a standardized tube rack. Guided by the barcode, tubes are delivered to the analyzer which "talks" to the lab’s LIS, to find out the tests to be performed. The analyzer performs the tests and results are sent to the LIS system.

This ideal system offers increased efficiency. With minimal manual intervention, the opportunity for human error is eliminated. If the automation pathway handles all sampling and processing, humans experience a minimum exposure to biohazards. And, since the barcode identity was established at the patient’s bedside, there are no identification errors.

The two keys to this system are the barcode sample identification and the automated sample handling of the NCCLS guideline of 5 mL to 10 mL-sized sample tube.

But when the patient is an infant or small child, the minimum sample is drawn and put in a non-standard collection tube that holds less than 1 mL of blood, like the BD Microtainer.

The barcode label will not conveniently fit on the small container in such a way to accommodate easy reading by automated pieces of equipment. The barcode is often applied horizontally forming a "flag," while most instruments require vertical reading. Nor does application of the barcode on the Microtainer allow an easy fit in a centrifuge.

The use of pediatric-size specimen collection tubes presents many stumbling blocks to laboratory automation. This precious sample does not fit in the standard sample trays either on automated sample movement devices or on many present-day versions of automated equipment.

Flowchart for Automated Sample Handling

Flowchart for Automated Sample Handling (Pediatric obstacles in red)

Challenges presented by small samples:

• Barcode labels do not fit
• Barcode cannot be read by instrument barcode readers
• Sample cannot be centrifuged without smashing the barcode
• Barcode cannot be electronically read if printed small
• Pediatric tubes do not fit in standardized sample trays and on instruments
• Sample probes do not fit inside the small pediatric tubes
• Manual specimen transfer leads to identification errors
• Manual specimen identification on some instruments may lead to errors
• Errors with putting the sample in the incorrect position on the sample tray
• Manually entering the incorrect accession number
• Manually ordering incorrect tests
• Broken "chain of custody" (identification)

The challenge is not only for pediatric samples, but also for geriatric and veterinary samples. This makes the market bigger and, hopefully, will encourage the vendors to develop better technology sooner.

 

Instrumentation

The challenges of instrumentation were addressed by several representatives. Many of them were well known to our presenters.

Dr. Nils B. Person, DPC, presented the solutions already in place on the IMMULITE 2000 continuous random-access analyzer units. This unit offers a large menu of assays so that many tests can be performed with one aspiration on a single instrument. The sample size for most assays is <50�L, with minimum dead space.

The sample rack accommodates the standard tubes and a 10 x 50 mm tube with special handling for sample volumes under 200 �L. The dead volume in the 10 x 50 mm tube is 50�L and the level-sensing probe is programmed to detect clots and to ensure adequate sample is available before aspiration, thus saving precious sample even if the test cannot be performed.

Carol Lee, from Beckman Coulter, covered both chemistry and hematology instrumentation. Considerations for using the smallest possible sample spanned a wide range. The average sample size ranges from 5 to 125 �L. Two hematology systems, the Gen*S and the Coulter� LH755, have on-board data management systems that allow both neonatal and pediatric decision rules.

Carol mentioned the micro tubes with false bottoms and sample rack adapters and tube adapters to hold 0.5 mL sample cups in place for automated sampling. The Synchron LX20 allows automated direct sample from open BD plasma microtainers and uses RF (radio frequency) level sensing for entry and exit level fluid sensing. Some instruments, like the Array/IMMAGE� Protein analyzers, allow multiple tests on a single dilution.

Carol emphasized the connectivity with the laboratory computer system as an important feature.

Kay Hytjan addressed Dade Behring’s solutions to the sample container issues of minimum dead volume, small sample size, autodilution capability as well as barcode identification. She spoke of the one-piece barcode capable SSC* and the Sufficient Sample Detect alert.

The Dimension system is the consolidated solution offering a menu in excess of 95 tests, including an open channel for home brewed tests such as caffeine. Dade recognizes future challenges such as adapting to new tube sizes and types, direct sampling from the small containers used to collect these precious samples, rapid return of tubes so the sample can be shared by multiple instruments, and onboard aliquot storage for follow-up testing.

The CHILDx group was very pleased to hear about their pediatric reference range study. The study, completed on the Dade Behring Dimension RxL by the Children’s National Medical Center in Washington D.C., covers 47 analytes.

The CHILDx group is also addressing this challenge in its own Pediatric Reference Interval study. Serum, urine and plasma samples are being collected from children 7 to 17 years of age, with 120 samples per gender per year of age. A physical examination, medical history and Tanner stage will be included with each sample. The IRB has given initial approval for 30 analyte assays.

Jim Shaw from Ortho Clinical Diagnostics highlighted the features of the Vitros 1.5FS Clinical Chemistry System. Many commonly ordered pediatric tests use only 5 – 7 �L. The key to the fluid handling on the Vitros is pressure monitoring. The MicroSensorTM Technology sample probe can detect fluid levels. If a clot, bubble or a short sample is detected during aspiration, the system activates the "Save the Sample" process so none of the small sample is lost. The MicroSensor. Technology reports indices of hemolysis, icterus, and turbidity without additional sample, reagents, or disposables. The 2D barcoding system can read smaller labels and is less sensitive to label orientation than the standard method. 

Clearly, all of the companies recognize the challenges present in automating small pediatric samples for testing.

 

Automation Technology

Anne Tate introduced CHILDx members to the LABInterLink automation system, an open solution that can adapt to multiple manufacturers’ instruments. 

The key to automation using LAB-InterLink is the patented Specimen Carrier, a Biohazard Containment vehicle with Positive container ID linking the stations. The specimen carrier was designed for 12 x 75 to 16 x 100 mm tubes. The sample barcode is linked to the carrier barcode as it travels through the automated system. The specimen carrier will be adapted to accommodate the smaller pediatric containers, possibly by using plastic false-bottomed inserts to carry the smaller container.

LAB-InterLink software can be programmed for specific scheduling, and routing decisions for pediatric specimens. The company will work with IVD manufacturers for sampling directly from a track system.

 

Blood Collection Solutions

While the previous speakers concentrated on how the sample was handled for testing, the BD representatives addressed issues surrounding sample collection. Dr. Lawrence acknowledged that as laboratory practice has becoming more complex, it requires more customer education on how to properly use blood collection products. Pediatric blood collection improvements include push button blood collection sets and using Microtainer type containers.

BD recognizes the need for, and is working on, a low volume, low-draw tube that will adapt to a standard barcode to fit most automated systems. Potential designs employ a thick wall tube, a false bottom or an adapter. The solution is still on the drawing boards.

The future products will include a product for collection of venous blood and separation of mononuclear cells, or separation of undiluted plasma for use in molecular diagnostic tests. BD and QIAGEN are working together to develop Preanalytical Molecular Diagnostics products for DNA and RNA testing.

The BDid Dx Specimen Management System is a system linking the bedside with the laboratory to minimize errors in specimen collection and sample identification. The system uses the barcoded patient ID to identify the patient, specify the tubes to be drawn, and provide labels. Bedside labeling ensures the right sample was drawn for the right patient. Standardized labeling is compatible with laboratory automation. The system interfaces with the Laboratory’s Information System and provides management reports. Statistics generated from beta test sites demonstrate over 70% reduction in errors.

After each presentation, the panel discussion centered around barcoding issues.

Barcodes are not universal even in a hospital. For a single barcode system to work in any institution it must meet the needs of the AABB for transfusion requirements as well as the laboratory equipment manufacturers. It must be large enough to be read on most readers and yet small enough to fit on the pediatric samples. Barcode readers must be generic enough to recognize all symbologies. Barcode printers will need to improve to meet these needs.

Several non-barcode approaches were brought up for specimen identification. The most radical was discussion of a subcutaneous Radio Frequency (RF) chip, similar to what is used in dogs and cats. The group recognizes this solution is not acceptable to most people at this time, however it would provide a better patient identification system than we currently employ.

 

Conclusion

Successfully Meeting the Challenge of Pediatric Sample Size in Laboratory Medicine brought into focus that the goal for improved testing on pediatric patients is a multifaceted challenge. As each partner in this matrix solves an individual challenge, the entire framework must adapt to incorporate the change.

Solving these challenges will require cooperation with all stakeholders ranging from the hospitals, to diagnostic manufacturers to our regulatory agencies.

The solutions will benefit a larger population than just the pediatric patient. While the number of children’s hospitals in the US is only 71, the challenges these institutions face are common to all of the institutions serving babies, children, and adults.

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This summary of Successfully Meeting the Challenge of Pediatric Sample Size in Laboratory Medicine, a symposium held in May 2003, was prepared by Jeanne Panlener, B.S., MT(ASCP)NM., a member of the CHILDx committee. She brings 30 years of hospital laboratory and diagnostic manufacturing experience to her role as Product Team Manager for ARUP Laboratories. This article was reviewed by Dr. Ron Weiss.

Some of the contributors are listed below.

[The Editor]

 

• DPC Instrument Systems Division
  Nils B. Person, PhD, FACB
  A. Paul Durham
  Art Smith

• Ortho-Clinical Diagnostics, a Johnson & Johnson
  Company
  Jim Shaw
  Ron Niederhauser

• BD Vacutainers PAS
  Jeffrey B. Lawrence, MD
  Cathy Shea, MT(ASCP)

• Beckman Coulter
  Carol Lee
  

• LAB-InterLink, Inc
  Ann Tate

• Dade Behring
  Kay Hytjan

• CHILDx
  Cheryl M. Coffin, MD
  Ron Weiss, MD, MBA
  Phillip R. Bach, PhD
  Jeanne Panlener, BS, MT(ASCP)NM