Technologies often develop more quickly than regulatory agencies can respond. This is especially true in clinical laboratories due to the rapid pace of new technological breakthroughs in diagnostics and therapeutics. Technologies and techniques that drive liquid delivery are no different. In the face of advancing capabilities of liquid-delivery instrumentation, increasingly complex tests, and an industrywide push for greater efficiency, a growing need for enhanced liquid-delivery quality assurance has emerged, as has a solution. The photometric method—the latest addition to the laboratory quality-assurance tool kit—measures light absorption to verify the performance of liquid-delivery instrumentation with a high degree of accuracy and precision, and is especially effective at low volumes. Although the trend toward low-volume testing is not new, until recently, there was no official guideline or recommendation for photometric calibration of liquid-delivery devices. The International Organization for Standardization (ISO) changes this with the approval and publication of a new standard, ISO 8655-7, formally making this advanced and convenient methodology an internationally accepted, standard method. Through ISO 15189 and ISO 17025, this new standard is applied to clinical laboratories.

Photometry and ISO 8655-7
ISO 8655-7 asserts that the photometric method “may be the method of choice” in ensuring the performance of piston-operated volumetric apparatuses, which include manual and automated liquid-delivery devices. Previously, gravimetry was the only ISO-approved method for liquid-delivery calibration. However, ISO acknowledged that this method, which weighs liquid quantities on balances, has limitations, especially at low volumes. Gravimetry also has limited applicability to multichannel device-performance verification, providing only an aggregate assessment of all channels as opposed to each individual channel. The gravimetric method further impedes testing by end-users because it requires a controlled environment to function properly. Due to several trends in clinical laboratories, such as smaller test volumes, faster turnaround time, and increasing use of multichannel devices, gravimetric calibration is becoming more inefficient.

ISO Technical Committee 48 recognized that laboratories were in need of a new methodology to minimize uncertainty in liquid-delivery verification, particularly at low volumes. For this reason, the organization evaluated and consequently approved photometry for the assessment of equipment performance. Relying on known light-absorption properties at specific wavelengths, photometric methods can provide stronger ensurance of data integrity, quickly and conveniently.

A highly accurate and precise application of photometry with a dual-dye approach to calibration is described in Annex A of the ISO 8655-7 standard. Called Ratiometric Photometry™, this technique employs two highly characterized solutions to combat accuracy problems typically associated with low-volume measurement, yielding results with uncertainty less than 1% for volumes as low as 0.1 µL. Furthermore, Ratiometric Photometry can be traced to a National Standard (NIST), providing clinical laboratories with the high degree of accuracy assurance required in testing human samples.

Demands on Laboratories
ISO’s approval of the photometric method for calibration answers the demands that many clinical laboratories are currently facing. A mounting focus on quality is one such demand. Driven by quality demands, process controls, and advancing Clinical Laboratory Improvement Amendments (CLIA) and similar state standards, clinical laboratories have been tightening quality-control programs.

The heightened focus on laboratory productivity makes accurate and precise volumetric measurement more crucial than ever. This is especially true as laboratories work with smaller liquid volumes. Laboratories are seeking new and superior methods to validate the performance of their liquid-handling instrumentation to avoid inaccurate sample testing as well as to maximize investment in automated equipment by enhancing its productivity.

The cost of inefficiency is not the only price that clinical laboratories pay for malfunctioning liquid-delivery instrumentation. Dispensing samples in volumes inaccurate by even miniscule amounts can alter concentration and prevent the identification of disease or harmful substances in samples. These false negatives may result in improper diagnoses, the consequences of which cannot be fairly measured. For example, imagine the consequences of a missed diagnosis of avian flu.

The cost of false-positive results in clinical laboratory testing must also be considered. False reactions can also lead to incorrect diagnoses and unnecessary therapeutic treatment. Accurate liquid-delivery methods can strengthen the confidence that clinical laboratories have in the results of their testing, avoiding improper patient care.

The scarcity of laboratory resources, particularly qualified medical technicians, is another trend driving the need for enhanced liquid-delivery quality assurance. The reduction in degree programs and specialty training for medical laboratory professionals, and growing workloads, put a high demand on efficiency, productivity, and quality. Tests must be done correctly the first time to avoid inefficient and costly retesting. Photometric calibration gives technicians an easily implemented and user-intuitive tool for prompt performance verification to ensure test quality.

The Role of ISO Regulations
In the constantly evolving health sciences industry with new challenges and solutions emerging every day, it is often difficult for laboratories to know which technologies are passing, risky fads and which are solid, reputable solutions. This is the benefit that international standards-development organizations, such as the ISO, bring to the industry. These agencies invest time and resources into evaluating and approving standards that will impact and improve industry practices. Incorporating internationally accepted methodologies into laboratory standard operating procedures brings several advantages.

First, clinical laboratories can also reduce risk by implementing a proven and internationally accepted quality-assurance technology. This will prove useful during regulatory audits; in building client and consumer confidence; and in striving to comply with CLIA regulations and to ISO 17025, the international laboratory quality standard for calibration and testing. These standards support the preferential use of standard methods such as the photometric approach.

Integrating ISO-approved standards in the clinical laboratory can also be leveraged as a first-mover’s advantage over competition. While American clinical laboratories have traditionally turned first to CLIA for guidance, American regulations are evolving toward greater harmonization with their international counterparts. For example, the laboratory quality standard ISO 17025 was initially adopted most widely in Europe, but, stimulated by international treaty, has become the standard for American food-testing laboratories. It is also being adopted on a voluntary basis throughout specialty laboratory networks in the United States, including environmental and water-quality testing and food and beverage testing. The ISO’s adoption of the photometric method for liquid-delivery calibration is predicted to be followed by broad American acceptance. US laboratories can act now to mold their laboratories to ISO standards.

Productivity-Enhancing Solution
Even slight volumetric discrepancies can compromise laboratory test data integrity, leading to failed tests, higher costs associated with retesting and remedial actions, useless data, and inefficiency. In the ever-growing push for enhanced productivity, clinical laboratories are seeking to maximize performance of their liquid-delivery instrumentation. The International Organization for Standardization has validated a new tool to do so, standardizing the photometric method and noting that it is particularly well-suited for calibration of low volumes. Additionally, the photometric method can be more easily adapted to measure single- and multichannel automated liquid-delivery equipment, helping to ensure quality data from increasingly complex tests.

George Rodrigues, PhD, is senior scientific manager at ARTEL, an innovator in liquid-delivery quality assurance.