Improved molecular laboratory productivity by consolidation of testing on the new random-access analyzer Alinity m

Study design

This international, multicenter study compared the workflows, comprising receipt, preparation, and analysis of samples for HIV-1, HCV, HBV, HR HPV, and STI (CT, NG, Trichomonas vaginalis [TV], and Mycoplasma genitalium [MG]) assay analytes, performed on Alinity m and various analyzers widely used in clinical laboratories.

The study utilized either simulated specimens (six study sites) or residual de-identified patient specimens (two study sites) using the respective laboratory’s sample arrival pattern for testing on Alinity m. Clinical samples for routine testing consisted of serum, plasma, liquid-based cytology medium, urine, and various swab specimens, including oropharyngeal, vaginal, endocervical, urethral, and rectal swabs. Residual patient specimens (where applicable) were sourced per site policies, procedures, and applicable local regulations, including approval by the site’s Independent Ethics Committee (IEC) or waiver.

Participating study sites

The study was conducted at eight independent International Standard Organization (ISO)-certified clinical laboratories (Table 1) in Berlin, Germany (Medizinisches Infektiologiezentrum Berlin); Aachen, Germany (PZB Aachen); Padua, Italy (Padua University Hospital, Padova); Madrid, Spain (Hospital Universitario Ramón y Cajal); El Prat de Llobregat, Spain (Laboratori de Referencia de Catalunya); Glasgow, UK (West of Scotland Specialist Virology Centre); Creteil, France (Hospital Universitaire Henri Mondor); and Johannesburg, South Africa (Lancet Laboratories). The clinical laboratories comprised a mix of hospital-based and privately-owned entities.

Analyzers

At each study site, one Alinity m analyzer was used to compare the workflow against multiple routine analyzers. The routine analyzers included in the study and their key features are summarized in Table 1 and Supplemental Table S1, respectively. The Alinity m (Abbott Molecular, Des Plaines, IL, USA) is a fully automated, continuous, random-access molecular diagnostic analyzer using real-time PCR and ReadiFlex^® technology [12]. It is a floor analyzer with a processing capacity of 300 samples in approximately 8 h, and has an amplification reagent capacity of 20 reagent packs, which can be stored on-board for 30 days. The time to first result is <2 h and the ReadiFlex technology enables the system to run statum (STAT) samples.

Samples and testing procedures

Clinical samples were received at each laboratory in accordance with their established criteria for respective sample types over a period of 5–15 days. Clinical specimens for the requested analyte were tested on the routine analyzers and held at either 4–8 °C or frozen at −20 °C/–70 °C for long-term storage. Requested tests and the date and time of sample arrival, sample onboarding, sample aspiration, and result reporting were documented. Batch testing on routine analyzers required clinical samples to be sorted, stored, and frozen until sufficient numbers of samples were collected to maximize reagent usage and minimize waste. Alinity m provides random-access capabilities; therefore, sorting, storing, freezing, and thawing procedures were not required. Assays were run per each laboratory’s testing SOP and performed per the manufacturers’ package insert instructions. Testing on the Alinity m instrument was conducted in accordance with the Alinity m System Operations Manual, assay-specific application files, assay-specific instructions for use, and the study protocol.

The Alinity m workflow at six sites used parallel water samples to simulate sample arrival in the laboratory. At study site 3, consecutive clinical samples received by the laboratory were split into two aliquots. The first aliquot was tested with the routine analyzer per laboratory procedures while the second aliquot was tested immediately on the Alinity m analyzer. At study site 6, consecutive clinical samples received by the laboratory were first processed according to the routine workflow. To simulate a routine workflow on Alinity m, samples of a specific testing day were de-identified and processed on Alinity m based on their documented arrival times. Additionally, at three study sites, priority samples were received (or arbitrarily defined) and tested as STAT samples on the Alinity m platform and, if available, on the comparator routine analyzer to evaluate the impact of STAT requests on workflow metrics.

Workflow metrics

Three time periods (Figure 1), reflecting the major aspects of workflow in the clinical laboratory, were measured for the routine analyzers and Alinity m: (i) “Total TAT” was defined as the time from arrival of samples into the molecular diagnostic laboratory to result reporting by the analyzer; this period included all pre-analytical procedures (e.g., centrifugation, storing, sorting, freezing, and thawing to batch samples, if applicable); (ii) “Sample onboard TAT” was defined as the time period from sample loading and automated or manual start of testing (depending on the analyzer) to result reporting by the analyzer; and (iii) “Processing TAT” was defined as the time period from sample aspiration by the analyzer to result reporting by the analyzer; this measure focused on analyzer performance and was only assessed for Alinity m.

Figure 1:

Workflow metrics for the various aspects in the clinical laboratory.

Three turnaround time (TAT) periods were measured for routine analyzers and Alinity m. The processing TAT metric was only measured for Alinity m.

Evaluation of TATs

Total TAT and sample onboard TAT using the standard workflows on multiple routine analyzers (study sites 1–5) or on the batch workflow analyzer m2000 (study sites 6–8) were compared to those of Alinity m. Sample onboard TAT of STAT samples was assessed for Alinity m at three study sites and compared to the Panther (Hologic, Inc. Massachusetts) system at one study site. Evaluation of processing TAT on Alinity m was conducted “AT” all study sites.

Study site 3 conducted an additional evaluation of TATs comparing two Panther analyzers to a single Alinity m analyzer using fresh clinical specimens over a period of two days. Since each Panther analyzer can run a maximum of four different assays, the site compared two Panther analyzers to one Alinity m analyzer to accommodate continuous testing of the six analytes per study protocol. Panther 1 was dedicated to running the Aptima CT/NG and Aptima MG assays. Panther 2 was dedicated to running the Aptima HIV-1, HCV, and HBV assays. Analyzer-specific racks were loaded onto the analyzers simultaneously. Result reporting times from the analyzers were recorded for all samples.

Total TATs for routine analyzers and Alinity m (Abbott)

We examined the total TATs (i.e., from sample arrival at the laboratory to result reporting) for standard workflows of multiple clinical routine analyzers compared to Alinity m (Table 2). Total TATs for Alinity m ranged from 5 to 29 h for 100% of results, compared to standard workflows on routine analyzers, which ranged from 4 to 21 days (Table 2 and Supplemental Figure S1). A period of 21 days for total TAT was observed at study site 2; this result was a function of their routine workflow for HPV diagnosis, which includes batching every 10 days as only a few samples are analyzed with the digene HC2 HPV DNA (Qiagen, NV) test. Total TATs for routine analyzers varied by requested assay (Figure 2A, C, E, G, I, K, M, O), whereas total TATs for Alinity m were consistent, rapid, and independent of the requested assay (Figure 2B, D, F, H, J, L, N, P).

Figure 2:

Total turnaround time (TAT) with the consolidated, continuous, random-access workflow of Alinity m analyzer compared to the standard workflows of multiple routine analyzers.

Total TAT was defined as the time from sample arrival in the laboratory until reporting of results. Data are presented as time to completion for the cumulative percentage of samples. Left panels: total TATs broken out by assay for the routine analyzers. Right panels: total TATs broken out by assay for the Alinity m analyzer (HIV is shown in blue; HCV, red; HBV, green; STI, purple; and HPV, orange). Study site 1 (A, B; n=860); study site 2 (C, D; n=1047; STI: CT/NG/TV [solid line], MG [dashed line]); study site 3 (E, F; n=1,109; STI: CT/NG [solid line], MG [dashed line]); study site 4 (G, H; n=135), study site 5 (I, J; n=248; HIV: cobas 4800 [solid line], cobas 6800 [dashed line], CAP/CTM [dotted line]), study site 6 (K, L; n=1,911), study site 7 (M, N; n=673), and study site 8 (O, P; n=472).

Sample onboard TATs for multiple routine analyzers compared to Alinity m

In evaluating sample onboard TAT, routine analyzers used at each study site reported results for all ordered tests with overall sample onboard TATs ranging from 7.00 to 32.50 h across testing sites 1–5 (medians of individual sample onboard TAT ranged from 4.13 to 6.25 h; Table 2). Sample onboard TATs were dependent on the number of samples, tested analyte, and analyzer used (Figure 3A, C, E, G, I). The Alinity m analyzer at each site reported results for all tests ordered with overall sample onboard TATs ranging from 2.75 to 6 h (medians of individual sample onboard TATs ranged from 2.20 to 2.98 h) in a continuous manner, independent of the analyte tested (Figure 3B, D, F, H, J).

Figure 3:

Comparison of sample onboard turnaround time (TATs) with multiple routine analyzers vs. the consolidated workflow of the Alinity m analyzer.

The time from sample onboarding to result reporting on the Alinity m analyzer compared to the time from the start of processing to result reporting with multiple routine analyzers at eight study sites for the various assays shown: study site 1 (A, B; n=1,229); study site 2 (C, D; n=1,047; *15 additional HPV results were obtained after 32 h); study site 3 (Phase 1; E, F; n=1,109); study site 4 (G, H; n=135); study site 5 (I, J; n=248); study site 6 (K, L; n=1911); study site 7 (M, N; n=673); and study site 8 (O, P; n=614).

Sample onboard TATs for the m2000 analyzer and Alinity m

The m2000 (a batch analyzer) at testing sites 6–8 reported results for all ordered tests with overall sample onboard TATs between 7.25 and 9.00 h after samples were loaded (medians of individual sample onboard TATs ranged from 5.82 to 7.33 h; Table 2 and Figure 3K, M, O), whereas Alinity m (a continuous, random-access analyzer) completed result reporting for all ordered tests between 3.75 and 5.75 h after samples were loaded (medians of individual sample onboard TATs ranged from 2.43 to 3.43 h). The sample onboard TATs on Alinity m were independent of the tested analyte (Table 2 and Figure 3L, N, P).

Sample onboard TATs for Panther analyzers and Alinity m

At study site 3, TATs from sample onboarding to result reporting for various tests requested using the routine workflow were compared for two Panther analyzers and one Alinity m analyzer. On day 1, 180 samples were processed utilizing the two Panther analyzers in 8.68 h compared to 8.00 h for Alinity m (Figure 4). On day 2, an analysis of an additional 169 samples was completed in 7.13 h on the two Panther analyzers, compared to 6.33 h on Alinity m (Supplemental Figure S2).

Figure 4:

Time to result with two random-access Panther analyzers compared to one Alinity m analyzer with ReadiFlex technology testing the same workload (study site 3, day 1, n=180 samples).

“Number of results” is the order in which results were generated by each system. The lighter shaded area represents a combination of tests on the two Panther analyzers, and the darker shaded area represents the tests run on Alinity m. Colored blocks represent the tests run on the different analyzers.

Alinity m processing TATs

To further explore the consistency of result reporting of Alinity m in a random-access testing mode, we compared processing TATs on Alinity m analyzers across the eight laboratories (n=7,476). All tests ordered on Alinity m had results reported within a range from 113 to 117 min, with 95% of all ordered tests reported in 115 min (Figure 5). Processing TATs were independent of the assay combination and were consistent across the eight laboratories. None of the comparator routine analyzers were capable of simultaneously processing the above assay combination [11], [13].

Figure 5:

Processing turnaround time (TAT) for Alinity m per assay.

Processing TAT, defined as the time from sample aspiration until result reporting, was determined for a total of 7,476 samples run on Alinity m analyzers across all eight study sites.

Alinity m STAT sample processing

A total of 3,754 samples were tested across three study sites; of these, 3.4% of samples (n=126) were ordered as STAT samples. The mean sample onboard TAT for STAT samples on Alinity m was 2.36 h (±0.19 h standard deviation). The sample onboard TATs of routine samples loaded on Alinity m were not affected by prioritizing STAT samples (Figure 6).

Figure 6:

Comparison of routine vs. STAT sample onboard turnaround time (TATs) on Alinity m.

A total of 3,754 samples including 3.4% STAT samples (n=126) were tested across three study sites. STAT samples are indicated in green.

In a direct comparison at one site, the sample onboard TATs for three STAT STI samples tested on Alinity m were 2.48, 2.33, and 2.48 h, compared to 4.28, 4.85, and 4.37 h on the Panther analyzer. A STAT HIV-1 sample had a sample onboard TAT of 3.28 h on Alinity m compared to 3.78 h on Panther.