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Abstract INTRODUCTION:
When modifying a current lab developed test (LDT), the focus is often directed toward simplification, cost-reduction, and improving robustness. However, this leaves another aspect of redevelopment significantly overlooked: adding laboratory operational efficiency. Increasing laboratory operation efficiency can dramatically reduce labor, eliminate hazardous chemical consumables, and increase throughput. The gains provide additional resources that may be used to expand the current test catalogue or to increase the current volumes for existing tests. This all can be accomplished when re-developing tests with subpar performance though combining several existing tests into one, aligning workflows across different tests, and/or reducing turn-around-time to provide a more robust clinical test for both physicians and patients. Here are a few examples of strategies for the re-development of tests to improve laboratory operation efficiency.
METHODS:
Three primary strategies were evaluated. First, was the complete re-development of problematic legacy tests to move away from time-and labor-intensive liquid-liquid extraction (LLE) methods. Second, tests with similar properties were combined into single panels. Third, when consolidation was not feasible, tests were aligned through re-development to maximize process commonality. This included establishing simplified extraction methods, standardizing mobile phases, identifying “universal” columns, and utilizing identical systems across tests. Furthermore, modern technologies were incorporated into these workflows, such as Solid Phase Exaction (SPE) and Supported Liquid Extraction (SLE) automation.
RESULTS:
The first strategy involved the complete redevelopment of a labor and time intensive test, Delta 9-Carboxy-Tetrahydrocannabinol in urine. The original method utilized LLE via a pressure manifold, a process requiring 3–4 hours to extract 48 samples. This workflow necessitated three full-time employees across three shifts to maintain volume. Due to high labor and consumable demands, inconsistent results, frequent repeats, the test was prioritized for redevelopment. The new method employs a "dilute-and-shoot" approach in a 96-well plate format. This transition reduced extraction time to 45 minutes with minimal solvent usage. Most significantly, the streamlined workflow now allows a single technologist to manage the entire testing process with ease.
The second strategy focused on maximizing LC-MS/MS instrument utilization through the consolidation of Vitamin A and Vitamin E testing. Historically, these two analytes were extracted using the same method but required separate chromatography columns, distinct mobile phases, and different LC configurations (with Vitamin A utilizing an additional Turboflow column while Vitamin E did not). Consequently, each test occupied a dedicated LC-MS/MS instrument for an entire shift. Given that over 75% of these tests are ordered concurrently and share similar lipophilic properties, a unified method was developed. By optimizing the chromatography using a biphenyl column and a simplified mobile phase (0.1% formic acid in water and 0.1% formic acid in acetonitrile), we successfully merged the tests without altering the extraction process. This implementation reduced labor by 0.5 FTE and successfully freed one instrument for additional testing capacity.
The third strategy focuses on workflow improvement and better utilization of instruments when direct test consolidation is restricted by chemical properties. The target analytes, PLP and PA, presented significant challenges due to their extreme polarity and poor column retention, making a single combined injection difficult. Instead of a full merger, we elected to align the two methods. By modifying the PA test to mimic the PLP workflow (including identical extraction protocols, columns, and mobile phases) we were able to utilize the same LC-MS/MS instrument for both. By simply adjusting the LC gradient to ensure adequate separation for PA, we enabled a sequential injection strategy where PLP is injected first using its specific gradient, followed immediately by injection of PA. This alignment eliminated the need for separate extraction trays (if both PLP and PA ordered), preventing the downtime associated with switching columns and mobile phases, and significantly reduced the risk of human error.
Due to its low barrier to implementation and high success rate with the PLP and PA tests, this harmonization strategy was subsequently applied to several other tests. This included aligning Nicotine in serum with Nicotine in urine via SPE, and Aldosterone in urine with Aldosterone in serum using SLE. Furthermore, the integration of the Biotage Extrahera™ automated platform into the extraction process further streamlined these workflows. All the redeveloped tests yielded consistently positive outcomes, collectively resulting in a dramatic improvement in overall laboratory operational efficiency and throughput.
CONCLUSION:
By shifting the focus of LDT modification from simple maintenance to operational excellence, we have successfully transitioned several high-volume tests from labor-intensive legacy methods to streamlined, automated workflows. This initiative was driven by three core strategies designed to reduce costs, minimize human error, and maximize instrument throughput. Through these strategic re-engineering efforts, the laboratory has moved beyond mere cost-reduction. We have established a robust, highly automated environment that minimizes organic solvent waste, reduces turnaround time (TAT), and significantly lowers the risk of manual error. Most importantly, these efficiencies have unlocked internal capacity, allowing the laboratory to scale current volumes and implement new clinical tests without a proportional increase in headcount or instrumentation.
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= Discovery stage. (57.21%, 2026)
= Translation stage. (23.38%, 2026)
= Clinically available. (19.40%, 2026)
