# Increasing Efficiency and Quality by Consolidation of  Clinical Chemistry and

Authors: Paolo Mocarelli; Gary L. Horowitz; Pier Mario Gerthoux; Rossana Cecere; Roland Imdahl; Janneke Ruinemans-Koerts; Hilmar Luthe; Silvia Pesudo Calatayud; Marie Luisa Salve; Albert Kunst; Margaret McGovern; Katherine Ng; Wolfgang Stockmann
Journal: Journal of Automated Methods and Management in Chemistry
 (2008)

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## Abstract

MODULARANALYTICS Serum Work Area (in USA
Integrated MODULAR ANALYTICS, MODULAR ANALYTICS is a trademark of a member of the Roche Group)  represents a further approach to automation in the laboratory medicine. This instrument combines previously introduced modular systems for the clinical chemistry and immunochemistry laboratory and allows customised combinations for various laboratory workloads.
Functionality, practicability, and workflow behaviour of MODULAR ANALYTICS
Serum Work Area were evaluated in an international multicenter study at six laboratories. Across
all experiments, 236000 results from 32400 samples were generated using 93 methods. Simulated routine testing which included provocation incidents and anomalous situations demonstrated good performance and full functionality. Heterogeneous immunoassays, performed on the E-module with the electrochemiluminescence technology, showed reproducibility at the same level of the general chemistry tests, which was well within the clinical demands. Sample
carryover cannot occur due to intelligent sample processing. Workflow experiments
for the various module combinations, with menus of about 50 assays, yielded mean sample processing times  of
<38 minutes for combined clinical chemistry and immunochemistry requests; <50 minutes including automatically repeated samples. MODULAR
ANALYTICS Serum Work Area offered simplified workflow by combining various laboratory segments. It increased efficiency while maintaining or even improving quality of laboratory processes.


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## Body

## 1. Introduction

The  clinical laboratory
is arguably the frontrunner in applying
scientific discoveries and technical
innovations
to patient care.
For example,  there are not only far more tests readily available
now compared to just twenty years ago but also the tests themselves have
increased sensitivity and specificity (e.g., hs-CRP, ferritin). It has been
estimated that about 65% of medical decisions are based on laboratory tests [1].Paradoxically, the clinical laboratory success has placed it under even
greater pressure  to produce more and better test results, with shorter
turnaround times and at lower costs. As clinical laboratories have evolved,
they have relied heavily on automation. By moving from manual assays of single
analytes to random access, multichannel, automated instruments, and more tests
can be done, more frequently, with fewer people. As noted in recent
publications, by combining several of these instruments into a novel single
platform for the clinical chemistry [2] and
for the immunochemistry laboratory [3],
these analysers represented a new degree of consolidation.However, there has been little integration of traditional clinical
chemistry (ISE, spectrophotometry, homogeneous immunoassay) and heterogeneous
immunoassay. From an analytical and technology perspective, the separation of the two
types of analysers may make sense. But, from a medical perspective, of course,
the separation is entirely artificial. For the patient in the emergency room,
the physician needs to know the troponin and the potassium. For the oncology
patient, the physician needs to know the CEA as well as the calcium. Does it
make sense to draw two tubes of blood to insure quick turnaround time by
running the sample on two analysers simultaneously? Or, if just one tube is
drawn, is it the only solution to insure quick turnaround time by asking a
technologist to make sure that, as soon as the tube is finished on the
chemistry analyser, it gets placed on the immunoassay analyser to be analysed
there? With either scenario, there are inherent inefficiencies, as compared to
running a single tube on a single system for all the requested tests.
MODULARANALYTICS SWA (in USA: Integrated MODULAR ANALYTICS, IMA),
thereafter MODULAR system, represents the integration of comprehensive systems
for traditional clinical chemistry and for heterogeneous immunoassays into a
single system for essentially all chemistry analytes.Here we present the results of our studies at 6 laboratories with a
single system processing a selection of 30 to 50 different tests for clinical
chemistry, specific proteins, therapeutic drugs, and immunochemistry
determination.Our goals were to(1)
evaluate the functionality and
practicability of the analyser;(2)
determine whether improved efficiency
would be realized by integrating clinical chemistry with heterogeneous
immunoassay testing;(3)
test
for possible effects on the quality of results (reproducibility, carryover) due
to consolidation.
In addition, we predicted that there would be a reduction of sample
splitting, the elimination of multiple user interfaces, and a reduction of
hands-on labour.Experiments were performed on MODULAR system in five laboratories over a
period of five months. At a sixth site, a larger hardware configuration was
tested afterwards.


## 2. Materials and Methods

MODULARANALYTICS Serum Work Area combines previously evaluated
modular systems for clinical chemistry and immunochemistry: MODULAR
ANALYTICS〈D,P〉 and MODULAR ANALYTICS〈E〉 [2, 3].The MODULAR system consists of a control unit, a core unit with a bidirectional
multitrack rack transportation system, and four kinds of analytical modules—an ISE module for
the electrolytes Na, K, and Cl with a maximum throughput of 900 tests/hour, a
P800 module with a capacity of 44 spectrophotometric tests on board and a
maximum throughput of 800 tests/hour, a D2400 module with 16 spectrophotometric
tests and a maximum throughput of 2400 tests/hour, and an E170 module using the
electrochemiluminescence technology with a capacity of 25 immunochemistry
reagents on board and a throughput of up to 170 tests/hour. The configurations
of MODULAR system are versatile and allow customised module combinations for
various laboratory workload patterns. Of the several available hardware
combinations, three different combinations of the clinical chemistry modules D
and P and the immunochemistry module E were evaluated at the six sites (3〈PE〉, 2 〈PPE〉, and 1 〈DPE〉); all systems included an ISE
module. Figure 1 shows the schematic structure of MODULAR system.Figure 1
Schematic
structure of MODULAR system.The instruments used in the different laboratories for comparison with
MODULAR system during the workflow study were MODULARANALYTICS〈P〉,
〈PP〉, 〈E〉, Elecsys 2010
(Elecsys
is a trademark of a member of the Roche group), Hitachi 747 and 917, all from Roche
Diagnostics (Mannheim, Germany), the BNA II protein analyser from Dade Behring
(Liederbach, Germany), the ADVIA Centaur and ACS: 180 from Bayer (Tarrytown, NY, USA) and the AxSYM from Abbott Laboratories, (Abbott Park, Illinois,
USA).The methods selected for the workflow studies covering approximately 80
analytes with 30 to 50 applications per laboratory are summarised in Table1.
For the imprecision runs and functionality testing, only a subset of these
methods was processed at each laboratory. The reagents for MODULAR system were
the respective system packs from Roche Diagnostics. The calibration of the
tests was done according to the requirements set by the manufacturer using the
calibration materials from Roche Diagnostics. The daily quality control was
performed with control sera also provided by the manufacturer.Table 1
List of analytes used during the
performance evaluation and within-run imprecision for selected analytes (cells
with a CV number: analytes were used for within-run imprecision, x: analytes
were added for the workflow experiments; CS1 control serum PNU from Roche, HS
human serum pool, HU human urine pool, analyte concentrations within or
slightly above reference range; CS pool, control serum of a low- and high-level
control).
AssaysMethodUnitsMaterialLab 1 CV%Lab 2 CV%Lab 3 CV%Lab 4 CV%Lab 5 CV%Lab 6 CV%Qual-Spec CV%*Electrolyte assaysNASodium (ISE-indirect)mmol/lCS 10.30.40.30.30.70.40.3 (0.7)KPotassium (ISE-indirect)mmol/lCS 10.50.50.30.50.80.42.4CLChloride (ISE-indirect)mmol/lCS
10.40.50.40.40.60.50.7 (1.0)Enzyme assaysACPacid phosphataseU/lxx4.5ALP_AAlkaline phosphatase AMPU/lCS 10.93.4ALP_IAlkaline phosphatase IFCCU/lCS 10.7x3.4ALP_OAlkaline phosphatase optimizedU/lCS 1x1x3.4ALT_IAlanine aminotransferase IFCC, wo PypU/lCS
12.5x2.42.413.6ALT_IPAlanine aminotransferase IFCC, w PypU/lCS 12.5x13.6AST_IAspartate aminotransferase IFCC wo PypU/lCS 1x3.32.22.17.2AST_IPAspartate aminotransferase IFCC w PypU/lCS 1x2.17.2AMYAmylase total EPS (ethylidene protected substrate)U/lCS
10.7xx0.60.63.7P-AMYAmylase pancreatic EPSU/lCS
10.85.9CHECholinesterase (Butyrylthiocholine substrate)U/lxxxx3.5CKCreatine kinase, NAC activated (N-acetylcysteine)U/lCS
10.60.8xx0.7x20.7CKMBCK-MB—MB isoenzyme of creatine kinaseU/lCS
12.3xxxGGTγ-Glutamyl transferase (procedure by
Szasz-Persijn)U/lCS
1xx1.81.6x1.77.4GLDHGlutamate
dehydrogenaseU/lxxHBDHLactate
dehydrogenase-1-isoenzymeU/lxLDH_OLactate
dehydrogenase  DGKCU/lCS
1x0.4x0.7x3.9LDLactate
dehydrogenaseU/lCS
113.9LIPLipase
colorimetricU/lCS
1110.811.6Substrate assaysALBAlbumin (BCG, bromcresol green, plus)g/lCS 1x0.8x1.21.1 (2.8)D-BILBilirubin direct (Jendrassik)μmol/lCS
1xxxx1.8xT-BILBilirubin
total (DPD, dichlorphenyldiazonium method)μmol/lCS
1xxxx1.9x11.3CHOLCholesterol (CHOD-PAP)mmol/lCS 10.81.00.90.91.11.42.7HDLHigh-density lipoproteinsmmol/lCS 10.80.9x0.9x3.6LDLLow-density lipoproteinsmmol/lCS 10.6xx3.3CREAJCreatinine (Jaffé, rate blanked)μmol/lCS
12.41.41.91.11.82.2CREACreatinine (enzymatic, plus)-urineμmol/lxGLU_PGlucose (GOD-PAP)mmol/lCS
10.80.92.2GLU_HGlucose
(hexokinase)mmol/lCS 10.90.71.01.00.62.2FEiron (FerroZine method)μmol/lCS
10.5x0.71.2xx15.9LACTLactate (colorimetric)mmol/lCS 10.70.913.6TPTotal protein (biuret reaction)g/lCS 1x0.4xx0.8x1.4TGTriacylglycerol (GPO-PAP)mmol/lCS 11.11.30.91.21.20.711.5UREAUREA/BUN (UV, kinetic)mmol/lCS
11.81.41.51.61.31.76.3UAUric acid  (PAP, plus)μmol/lCS 1x0.51.60.61.01.04.2CO2Bicarbonate
(UV, kinetic)mmol/lCS
11.62.3 (4.9)CACalcium
(OCPC, ortho-cresolphthalein complexone)mmol/lCS 10.81.10.70.91.1x0.9 (1.5)MGMagnesium (xylidyl blue method)mmol/lCS
10.70.71.0x1.1 (2.6)PHOSPhosphorus
(molybdate, UV)mmol/lCS
1x1.1xx1.4x4Protein assaysGPROTα1-acid-glycoprotein (TIA, Tina-quant a)g/lHS Pool0.7x5.7ATRYPα1-antitrypsin (TIA, Tina-quant a)g/lx3.0MICGLβ2-microglobulin (TIA, Tina-quant a)μg/mlx3.0ASLOAntistreptolysin
O (LPIA, Tina-quant a)IU/mlHS Pool0.61.0C3cComplement
protein C3c (TIA, Tina-quant a)g/lHS Poolx1.3C4Complement
protein C4 (TIA, Tina-quant a)g/lxxCPLASCeruloplasmin
(TIA, Tina-quant a)g/lxCRPC-reactive
protein (TIA, Tina-quant a)mg/lHS Poolx0.8xx1.21.326.3FERRFerritin
(LPIA, Tina-quant a)μg/lHS Pool2.37.5HBA1C%Glycated haemoglobin A1c (TIA, Tina-quant a)%HS Pool1.1HGLOBHaptoglobin
(TIA, Tina-quant a)g/lHS Pool0.91.1x10.2IGGImmunoglobulin
G (TIA, Tina-quant a)g/lCS 1x2.52.02.61.91.9 (3.7)IGAImmunoglobulin
A (TIA, Tina-quant a)g/lCS 1x1.50.8x1.12.2 (3.8)IGMImmunoglobulin
M (TIA, Tina-quant a)g/lCS
1x1.71.7x1.32.3 (5.4)IGEImmunoglobulin
E (TIA, Tina-quant a)μg/lxxKAPPAKappa
(TIA, Tina-quant a)g/lxLAMBDLambda
(TIA, Tina-quant a)g/lxMYOMyoglobin
(TIA, Tina-quant a)μg/lxPALBPrealbumin
(TIA, Tina-quant a)IU/mlHS Pool2.25.5RFRheumatoid
factor (LPIA, Tina-quant a)IU/mlHS Pool0.50.80.60.94.3TRANSTransferrin
(TIA, Tina-quant a)g/lCS 1x1.51.4x1.9x1.5TDM assaysCARBCarbamazepine (CEDIA)μmol/lxDIGDigoxin (LPIA)nmol/lHS Pool2.03.8 (4.7)GENTGentamicin
II  (CEDIA)μmol/lxNAPANAPA
(CEDIA)μmol/lxPHENOPhenobarbital
II  (CEDIA)μmol/lxPHNYPhenytoin II  (CEDIA)μmol/lxPROCProcainamide  (CEDIA)μmol/lxSALSalicylate (iron complex)mmol/lxTHEOTheophylline
II  (CEDIA)μmol/lxVALPValproic
Acid II  (CEDIA)μmol/lHS Pool2.06.4Urine assaysNASodium (ISE-indirect)-urinemmol/lHU Pool0.40.60.40.614.4KPotassium (ISE-indirect)-urinemmol/lHU Pool0.40.80.41.29.0CLChloride (ISE-indirect)-urinemmol/lHU Pool0.81.30.60.6AMYAmylase
liquid-urineU/lHU Pool0.7xCREAJCreatinine Jaffé (rate blanked)-urineμmol/lHU Pool0.81.01.25.5CREACreatinine (enzymatic, plus)-urineμmol/lHU Pool0.95.5GLU_HGlucose (hexokinase)-urinemmol/lHU PoolxxUREAUREA/BUN (UV, kinetic)-urinemmol/lHU Pool1.91.21.41.5UAUric Acid  (PAP, plus)-urineμmol/lHU Pool0.90.90.7xCACalcium (OCPC, ortho-cresolphthalein complex.)-urinemmol/lHU Pool3.01.6x13.1MGMagnesium (xylidyl blue method)-urinemmol/lHU Pool1.0x19.2PHOSPhosphorus
(molybdate, UV)-urinemmol/lHU Pool1.21.6x9.0U/CSFProtein in urine/CSF(turbidim., rate)g/lHU Pool0.8x0.717.8MAUAlbumin
in urine (TIA, Tina-quant a)mg/lHU Pool1.3x18Immunochemistry
assaysT3Triiodothyroninenmol/lCS Poolx1.4x0.84.0 (4.7)T4Thyroxinenmol/lCS Pool2.7x1.53.4 (4.1)FT3Free triiodothyroninepmol/lCS Pool1.52.04.0FT4Free thyroxinepmol/lCS Poolx1.7xx0.93.8TSHThyroid-stimulating hormone, thyreotropinmIU/lCS Poolx2.10.81.11.10.68.1DIGITDigitoxinnmol/lCS Pool2.5DIGODigoxinnmol/lCS Pool2.83.8 (4.7)PROBNPN-terminal B-type natriuretic peptidepmol/lHS Pool0.5TNTTroponin
Tμg/lCS Pool1.01.1FERR_EFerritinμg/lCS Poolxx2.10.91.67.5FOLATFolatenmol/lCS Poolxxx3.91.7B12Vitamin
B12pmol/lCS Pool1.8xx2.6AFPα1-fetoproteinμg/lCS Poolxx0.9x1.8CA_125Cancer antigen 125kU/lCS Poolxxx0.91.06.8CA_153Cancer antigen 15-3kU/lCS Pool1.1xxx2.6CA_199Cancer antigen 19-9kU/lCS Pool0.9xx12.3CEACarcinoembryonic
antigenμg/lCS Poolxx1.21.34.6TPSATotal prostate-specific antigenμg/lCS Poolxx0.5x2.39.1FPSAFree prostate-specific antigenμg/lCS Pool0.81.0xCORTCortisolnmol/lCS Pool1.61.0x7.6DHEA-SDehydroepiandrosterone
sulfateμmol/lCS Pool2.5x1.7E2Estradiolpmol/lCS Pool1.61.7x1.710.9FSHFollicle stimulating hormoneIU/lCS Poolx0.91.3x5.1HCG +βHuman chorionic gonadotropin +β-subunitIU/lCS Pool1.81.21.2LHLuteinizing hormoneIU/lCS Poolx1.1xx6.2PROGProgesteronenmol/lCS Poolx1.29.8PRLProlactinmIU/lCS Poolx1.2xx3.5PTHParathyroid hormonepmol/lxxxINSInsulinpmol/lCS Pool2.31.67.6TESTOTestosteronepmol/l1.41.6x4.4*  References       [10, 11],
values in italics: from Ricós et al. [12];
values in parentheses: interim quality specifications.Depending on the analyte, either control material or human specimen
pools were used for theimprecision and routine simulation
imprecision experiments. Samples for the workflow experiments
included serum, heparinized plasma and urine from the daily routine.The performance evaluation was supported by CAEv, a program for Computer
Aided Evaluation [4].
This program allows the definition of experiments, the sample and test
requests, on-line/off-line data transmission, and the immediate data validation
by the evaluators.


## 3. Evaluation Protocol

### 3.1. Within-Run Imprecision

Two control materials (serum, urine) with
different concentrations of the analyte (or, for some analytes, a human
specimen pool at the diagnostic decision level) were used. The experiment was
performed on two days with 21 aliquots per run.


### 3.2. Precision in a Simulated Routine Run

Experiments for routine simulation are
designed for functionality testing of an analytical system in the clinical
laboratory. The protocol [5] has
proven to be a useful tool during various analyser evaluations [6].This particular experiment tests for potential systematic or random
errors by comparing the imprecision of the reference results (standard batch,n=15) with results from samples run in a pattern simulating routine sampling (randomized
sample requests, n>10). The randomized sample requests were simulated in
CAEv [4] according to each laboratory’s routine
sampling pattern. The samples were control materials or patient sample pools.
The number of requests varied with module combination, but was aimed at keeping
the analyser in operation for at least four hours. The second and third of the
three experiments processed at each site included provocation incidents like
reagent or sample shortage, barcode read errors, and various reruns.


### 3.3. Sample Carryover

Potential sample related carryover was investigated
using a slightly modified version of the Broughton protocol [7]. Only analytes with a very high physiological
concentration range were tested. Ideally, the ratio of the concentrations of
the high and low samples should be, depending on the analyte, 103 to
106. Three aliquots of a high concentration sample (h1,h2,h3) were
followed by measurements of five aliquots of a low concentration sample (l1⋯
l5) on each module.  The sequence h1⁢h2⁢h3 l1 l2 l3 l4 l5 was
repeated five times.Each sample was measured on the ISE module first, then on the D and/or P
module, and finally on the E170 module, thereby insuring that reusable pipette
probes were introduced multiple times prior to sampling on the E170 module,
where disposable (nonreusable) pipette tips are used. If a carry-over effect
from the ISE and D/P module sample probes exists, the l1 will be the most influenced, and the l5 will be the least influenced aliquot when
measured on E-module. The carry-over effects were compared with the imprecision
of the low concentration samples and the diagnostic relevance of the respective
E-module assays. Potential sample carryover of the following analytes was
tested: AFP, CEA, ferritin, anti-HAV, HBsAg, hCG + β, and t-PSA.


### 3.4. Workflow Study

The participating sites performed this study to
investigate whether or not MODULAR system met their routine laboratory specific
needs, especially for improved efficiency. As shown in Table2, module
combination, analyte assignment, tests per sample, numbers of samples, samples
per module, and tests per module, were very different at each laboratory. Three
methods were used to capture the test requests on samples so that the same
testing could be repeated on MODULAR system. Test requests were either
downloaded from the laboratory’s LIS to CAEv, captured directly by CAEv from
several analysers during routine operation or CAEv provided a “characteristic”
request list by simulation based on typical test frequencies and profiles of
the laboratory. In all cases, the same sample set, usually a predefined
substantial portion of a day’s workload was processed on MODULAR system.Table 2
Overview of processed workloads at the participating
laboratories.
(For explanation see materials and methods section, workflow study.)
SiteSWA config.Analytes processedAverage requests per sampleSample distributionTotal number of samples/ requestsRoutine compared1PE3  on ISE11 (1–36)CC
only:    232299 samplesYes,30  on PE only:        183281 requestsP800 +
E17011  on ECC + E:       492PPE3  on ISE11 (1–27)CC
only:    381555 samplesYes,41  on PPE only:        145839 requestsPP + 2*E201015  on ECC + E:     1604  on E20103PE3  on ISE9 (1–35)CC
only:    287399 samplesNo28  on PE only:        333422 requests17  on ECC + E:       794PE3  on ISE8 (1–21)CC
only:    318531 samplesNo26  on PE only:        874003 requests16  on ECC + E:     1265PPE3  on ISE6 (1–22)CC
only:    369573 samplesYes,39  on PPE
only:        633668 requestsH917 + H747 + 3 instr. with CLIA
+ RIA19  on ECC
+ E:     1416DPE3  on ISE9 (1–29)CC
only:  14281951 samplesNo12  on DE
only:        7716805 requests25  on PCC
+ E:     4463  on E(E2010 =
Elecsys 2010; Elecsys is a trademark of a member of the Roche group;
CLIA = chemiluminescence immunoassay; RIA = radio
immunoassay.)Samples were loaded on MODULAR system chronologically as they appeared
in the lab to mimic the laboratory’s routine pattern of receiving samples. All
relevant time steps and workload related activities like sample and reagent
handling, instrument preparation, loading and reloading of sample racks, and
technologist time (both hands-on and walk-away) were measured.


### 3.5. Practicability

Practicability of the system was assessed throughout
the study. A questionnaire—a supplement to
the general questionnaire [8],
which was previously used for the assessment of the single modules—was designed
especially for a consolidated sample working area. This allowed for a standardized
grading with the main focus on aspects of clinical chemistry and immunochemistry
consolidation and new software features.


### 3.6. Expected Performance

The protocol included expected performance criteria
which were agreed upon at the evaluators’ first meeting. The criteria for
imprecision were based on state-of-the-art performance, routine requirements of
the laboratories, and statistical error propagation [9].


## 3.1. Within-Run Imprecision

Two control materials (serum, urine) with
different concentrations of the analyte (or, for some analytes, a human
specimen pool at the diagnostic decision level) were used. The experiment was
performed on two days with 21 aliquots per run.


## 3.2. Precision in a Simulated Routine Run

Experiments for routine simulation are
designed for functionality testing of an analytical system in the clinical
laboratory. The protocol [5] has
proven to be a useful tool during various analyser evaluations [6].This particular experiment tests for potential systematic or random
errors by comparing the imprecision of the reference results (standard batch,n=15) with results from samples run in a pattern simulating routine sampling (randomized
sample requests, n>10). The randomized sample requests were simulated in
CAEv [4] according to each laboratory’s routine
sampling pattern. The samples were control materials or patient sample pools.
The number of requests varied with module combination, but was aimed at keeping
the analyser in operation for at least four hours. The second and third of the
three experiments processed at each site included provocation incidents like
reagent or sample shortage, barcode read errors, and various reruns.


## 3.3. Sample Carryover

Potential sample related carryover was investigated
using a slightly modified version of the Broughton protocol [7]. Only analytes with a very high physiological
concentration range were tested. Ideally, the ratio of the concentrations of
the high and low samples should be, depending on the analyte, 103 to
106. Three aliquots of a high concentration sample (h1,h2,h3) were
followed by measurements of five aliquots of a low concentration sample (l1⋯
l5) on each module.  The sequence h1⁢h2⁢h3 l1 l2 l3 l4 l5 was
repeated five times.Each sample was measured on the ISE module first, then on the D and/or P
module, and finally on the E170 module, thereby insuring that reusable pipette
probes were introduced multiple times prior to sampling on the E170 module,
where disposable (nonreusable) pipette tips are used. If a carry-over effect
from the ISE and D/P module sample probes exists, the l1 will be the most influenced, and the l5 will be the least influenced aliquot when
measured on E-module. The carry-over effects were compared with the imprecision
of the low concentration samples and the diagnostic relevance of the respective
E-module assays. Potential sample carryover of the following analytes was
tested: AFP, CEA, ferritin, anti-HAV, HBsAg, hCG + β, and t-PSA.


## 3.4. Workflow Study

The participating sites performed this study to
investigate whether or not MODULAR system met their routine laboratory specific
needs, especially for improved efficiency. As shown in Table2, module
combination, analyte assignment, tests per sample, numbers of samples, samples
per module, and tests per module, were very different at each laboratory. Three
methods were used to capture the test requests on samples so that the same
testing could be repeated on MODULAR system. Test requests were either
downloaded from the laboratory’s LIS to CAEv, captured directly by CAEv from
several analysers during routine operation or CAEv provided a “characteristic”
request list by simulation based on typical test frequencies and profiles of
the laboratory. In all cases, the same sample set, usually a predefined
substantial portion of a day’s workload was processed on MODULAR system.Table 2
Overview of processed workloads at the participating
laboratories.
(For explanation see materials and methods section, workflow study.)
SiteSWA config.Analytes processedAverage requests per sampleSample distributionTotal number of samples/ requestsRoutine compared1PE3  on ISE11 (1–36)CC
only:    232299 samplesYes,30  on PE only:        183281 requestsP800 +
E17011  on ECC + E:       492PPE3  on ISE11 (1–27)CC
only:    381555 samplesYes,41  on PPE only:        145839 requestsPP + 2*E201015  on ECC + E:     1604  on E20103PE3  on ISE9 (1–35)CC
only:    287399 samplesNo28  on PE only:        333422 requests17  on ECC + E:       794PE3  on ISE8 (1–21)CC
only:    318531 samplesNo26  on PE only:        874003 requests16  on ECC + E:     1265PPE3  on ISE6 (1–22)CC
only:    369573 samplesYes,39  on PPE
only:        633668 requestsH917 + H747 + 3 instr. with CLIA
+ RIA19  on ECC
+ E:     1416DPE3  on ISE9 (1–29)CC
only:  14281951 samplesNo12  on DE
only:        7716805 requests25  on PCC
+ E:     4463  on E(E2010 =
Elecsys 2010; Elecsys is a trademark of a member of the Roche group;
CLIA = chemiluminescence immunoassay; RIA = radio
immunoassay.)Samples were loaded on MODULAR system chronologically as they appeared
in the lab to mimic the laboratory’s routine pattern of receiving samples. All
relevant time steps and workload related activities like sample and reagent
handling, instrument preparation, loading and reloading of sample racks, and
technologist time (both hands-on and walk-away) were measured.


## 3.5. Practicability

Practicability of the system was assessed throughout
the study. A questionnaire—a supplement to
the general questionnaire [8],
which was previously used for the assessment of the single modules—was designed
especially for a consolidated sample working area. This allowed for a standardized
grading with the main focus on aspects of clinical chemistry and immunochemistry
consolidation and new software features.


## 3.6. Expected Performance

The protocol included expected performance criteria
which were agreed upon at the evaluators’ first meeting. The criteria for
imprecision were based on state-of-the-art performance, routine requirements of
the laboratories, and statistical error propagation [9].


## 4. Results

Across all experiments, 236000 results from 32400 samples were generated
using 93 methods.


### 4.1. Imprecision

The within-run imprecision met the expected performance criteria at
virtually all sites.
Typical within-run CVs for the enzyme and
substrate analytes were 1 to 2%, for the ion selective electrode (ISE) methods
0.5%, for the specific proteins and drug analytes 1 to 3%, for the urine
chemistry methods 1 to 2%, and for the heterogeneous immunoassays (with the
indication: thyroid, cardiac, anaemia, tumour markers and fertility) 1 to 3%
(Table1).


### 4.2. Functionality Testing

The six laboratories performed 44668 determinations during the random
part of the routine simulation covering 87 analytes in 733 series. CVs obtained
from theprecision in a simulated routine run experiment for the various
assay groups (ISEs, enzymes/substrates, urine analytes, proteins/TDMs, and
heterogeneous immunoassays) were summarized in distribution diagrams for the
reference (batch part) and random part (see Figure 2). Out of all 733 series,
13 (1.8%) showed higher CVs than the expected limit in the random part (9 in
the enzyme/substrate group, 2 in the urine and the immunoassay groups). Seven
of these CVs were only moderately increased (1 to 2% higher than the limit). Of
the remaining 6 series (5.3 to 22.8% CV), the highest CV was caused by an
unexplainable, nonreproducible outlier with a very low result in one series of
the albumin in urine test. With the outlier removed, the CV was 1.2%. In all
cases, the higher CVs were observed in only one of the three simulated routine
series per laboratory (with tests like lipase, uric acid, albumin in urine and
CA125) and there was no association with any malfunction of the instrument or
reagent. A software issue associated with the E-module masking/unmasking during
a provocation was also identified during these experiments (shift of the
results with the FT3 assay).Precision
in a simulated routine run; distribution of 733 within-run CVs in reference
(batch) and random parts; replicatesn in reference part 15 as follows:
(i) expected performance limit for within-run imprecision (solid line)
(ii) expected performance limit for randomised runs (dashed line).
(a)(b)(c)(d)(e)


### 4.3. Sample-Related Carryover

Table3 summarizes the carry-over effects seen when the high priority settings were intentionally turned off for a group of tests that were
considered high risk for sample carryover. Only results from laboratories with
the highest concentration ratio (high/low) are included in the table. For the 7
assays for which we expected to see sample-related carryover because of the
wide dynamic range of the analytes, our testing indicated potentially
clinically relevant problems with 5 (AFP, CEA, HBsAg, HCG + β, and t-PSA). By
utilizing the “high priority test” option, samples with requests for these
assays, which also had requests for ISE, D, and/or P module tests, were
automatically processed at the E-module first, eliminating the possibility for
carryover to occur for these samples and tests. In the other two (ferritin and
anti_HAV), neither criterion for carryover was met (more than 10% of the
(lower) medical decision level, or exceeding the 2 SD value). According to
investigations of the manufacturer, two additional carry-over sensitive
infectious disease assays were identified: anti-HBs and anti-HBc.Table 3
Sample related carryover withhigh priority test option off. With high priority test option on, sample carryover
cannot occur. (For explanation see results section, sample-related carryover.)
AnalyteExpected values10% of
lower
decision levelLower
detection
limitRatio
high : lowMax. diff
low1–low5(if >2SD)MaterialRelevant Carryover, high
priorityoffRelevant Carryover, high
priorityonAFP<6.2μg/l0.62μg/l0.6μg/l408710.62NativeyesNoCEA<4.6μg/l0.46μg/l0.2μg/l161977.64SpikedyesNoPSA<4μg/l0.4μg/l0.002μg/l7560.20SpikedyesNoFerritin~15–400μg/l1.5μg/l0.5μg/l9692.00SpikednoNoHCG +β<5 mIU/ml0.5 mIU/ml0.1 mIU/ml1170001.30NativeyesNoa-HAV<20 IU/l2.0 IU/l3.0 IU/l11840.25NativenoNoHbsAg<1.0 COI0.1
COI2851060.44nativeyesNo


### 4.4. Workflow

The module combinations (〈PE〉, 〈PPE〉, 〈DPE〉) and test
menu configurations used at the different laboratories were selected to meet
their specific workload demands. An overview is presented in Table 2. To
reflect true routine conditions, the samples were placed on the system in a
sequence mimicking the original arrival pattern in the laboratory, rather than
continuously, to test the system’s potential sample loading capacity. The
resulting cumulative throughput was up to 800 results/hour using 〈PE〉
module combinations and up to 1580 results/hour for 〈PPE〉 module
combinations. A throughput of approximately 2160 results/hour was yielded on
the 〈DPE〉 module combination in laboratory 6. In most of the
laboratories, the number of samples processed was not enough to reach the
system’s maximum throughput capacity.In addition to throughput, we looked carefully at sample processing time
(SPT), the time between sample registration (barcode reading on the instrument)
and the time the last result for that sample is produced. Note that SPT differs
from sample turnaround time (TAT), a commonly used term to describe the time
period from when the samples arrive in the laboratory and the availability of
the last result.The following mean sample processing
times were found for the different sample groups in five laboratories:(i)
13–18 minutes    for samples with general chemistry
requests only
(ISE + P or ISE + P1 + P2),(ii)
22–28 minutes for
samples with immunoassay requests only (E),(iii)
29–38 minutes for
samples with combined requests
(ISE + P + E or ISE + P1 + P2 + E).
The mean SPTs obtained with a 〈DPE〉 combination were comparable:
16 minutes for ISE + D + P, 26 minutes for E, and 27 minutes for ISE + D + P + E.We compared SPT of MODULAR〈PPE〉 with the current six dedicated
routine analysers for a predetermined time period, representing approximately
40% of a day’s workload in laboratory 5. Figure 3 shows that the time to
results for samples with clinical chemistry requests on MODULAR system is
comparable with that of the dedicated routine analysers (mean time 15 minutes,
80th percentile 20 minutes, maximum 38
minutes). Samples with combined requests for both
clinical chemistry and immunochemistry were
processed faster (mean time 34 minutes, 80th percentile 40 minutes, maximum 1 hour)
than on the dedicated analysers (mean time 46 minutes, 80th percentile 58 minutes, maximum 1.8 hours).Figure 3
SPT on
MODULAR system and dedicated routine analysers representing 40% of a daily
routine workload.Depending on test, module and number of
racks waiting in the rerun buffer, rerun results are reported 10–35 minutes after
availability of first results. An example of typical processing times to first
results and to final results (including rerun samples) is shown in Figure4.Figure 4
SPT with
focus on availability of rerun results.MODULAR SWA
supports “reflex
testing,” if the laboratory information system (LIS) offers this functionality.
Frequently practiced for certain indication fields, this feature allows the
automatic request of a further analyte, if a predefined concentration or
concentration range of the originally requested analyte is exceeded. Examples
are as follows: If TSH < 0.27 or > 4.2 mIU/L, FT4 is determined in
addition, if PSA > 4.0μg/L, free PSA is also measured and so on. Even
though it may no longer be as clinically relevant, reflex testing functionality
was assessed using a combination of P-and E-requests: CK → CK-MB(enzymatic) + TnT. The SPT for
such a sample with two additional reflex tests was increased by 30 to 55
minutes (Figure 5).Figure 5
SPT with
focus on reflex testing.Does thesample carry-over setting, which tags the assay in
question automatically as  high priority by the system, influence the
SPT? We compared samples having combined requests (on P- and E-module) with and
without  high priority assays. With  auto rerun off, there was no
result delay. The processing times were increased by 10–15 minutes with  auto
rerun activated, where processing on P module was delayed until final E-module
results were available.Maintenance and troubleshooting are activities which may also
considerably influence the daily workflow. For a modular system, the question
arises whether the entire system or only the affected module is blocked in
order to remedy a problem after, for example, asampling stop alarm.
This type of alarm results in the module discontinuing pipetting of samples.
The different time steps for two such alarms were monitored on a 〈PPE〉
combination at one site. For a provoked tip/vessel pickup-error on the
E-module, the elapsed time from getting the alarm, allowing the module to
finish the tests in process, taking the module down, then fixing the problem,
and getting the module back into operation was a total of 35 minutes; for a
provoked abnormal cap mechanism movement 22 minutes. While the E-module
was unavailable, the ISE and P-modules continued to process samples, and
samples requiring E-module tests were stored in the rerun buffer to be run
automatically when the E-module came back online.An important aspect of instrument consolidation on a single platform is
reduction in personnel hands-on time. In laboratory 5, we compared hands-on
time associated with MODULAR system with that of the 6 existing dedicated
analysers. As shown in Figure6, the operators saved about 10 hours based on
the sample workload; the main contribution was sample handling time. MODULAR
system was operated by 1 technologist while the 6 dedicated analysers required 3
persons.Figure 6
Hands-on
time on MODULAR system compared to dedicated routine analysers representing 40%
of a daily routine workload.One of the participating laboratories (laboratory 1) simulated a
workflow using MODULAR system as a dedicated immunoassay analyser. Tests
included 24 homogeneous tests (10 specific proteins, 6 therapeutic drug tests,
and 8 drugs of abuse tests) on P-module and 18 heterogeneous assays (thyroid,
cardiac, anaemia, and tumour markers) on the E-module, with samples loaded in a
simulated routine-type pattern. The average sample processing times for the
various request patterns were comparable with those mentioned previously
(<35 minutes).


### 4.5. Practicability

With the aid of a questionnaire, the practicability of MODULAR system
was graded as equally good (23% of all scores) or even better (68%) compared to
the evaluators’ currently used routine analysers.


## 4.1. Imprecision

The within-run imprecision met the expected performance criteria at
virtually all sites.
Typical within-run CVs for the enzyme and
substrate analytes were 1 to 2%, for the ion selective electrode (ISE) methods
0.5%, for the specific proteins and drug analytes 1 to 3%, for the urine
chemistry methods 1 to 2%, and for the heterogeneous immunoassays (with the
indication: thyroid, cardiac, anaemia, tumour markers and fertility) 1 to 3%
(Table1).


## 4.2. Functionality Testing

The six laboratories performed 44668 determinations during the random
part of the routine simulation covering 87 analytes in 733 series. CVs obtained
from theprecision in a simulated routine run experiment for the various
assay groups (ISEs, enzymes/substrates, urine analytes, proteins/TDMs, and
heterogeneous immunoassays) were summarized in distribution diagrams for the
reference (batch part) and random part (see Figure 2). Out of all 733 series,
13 (1.8%) showed higher CVs than the expected limit in the random part (9 in
the enzyme/substrate group, 2 in the urine and the immunoassay groups). Seven
of these CVs were only moderately increased (1 to 2% higher than the limit). Of
the remaining 6 series (5.3 to 22.8% CV), the highest CV was caused by an
unexplainable, nonreproducible outlier with a very low result in one series of
the albumin in urine test. With the outlier removed, the CV was 1.2%. In all
cases, the higher CVs were observed in only one of the three simulated routine
series per laboratory (with tests like lipase, uric acid, albumin in urine and
CA125) and there was no association with any malfunction of the instrument or
reagent. A software issue associated with the E-module masking/unmasking during
a provocation was also identified during these experiments (shift of the
results with the FT3 assay).Precision
in a simulated routine run; distribution of 733 within-run CVs in reference
(batch) and random parts; replicatesn in reference part 15 as follows:
(i) expected performance limit for within-run imprecision (solid line)
(ii) expected performance limit for randomised runs (dashed line).
(a)(b)(c)(d)(e)


## 4.3. Sample-Related Carryover

Table3 summarizes the carry-over effects seen when the high priority settings were intentionally turned off for a group of tests that were
considered high risk for sample carryover. Only results from laboratories with
the highest concentration ratio (high/low) are included in the table. For the 7
assays for which we expected to see sample-related carryover because of the
wide dynamic range of the analytes, our testing indicated potentially
clinically relevant problems with 5 (AFP, CEA, HBsAg, HCG + β, and t-PSA). By
utilizing the “high priority test” option, samples with requests for these
assays, which also had requests for ISE, D, and/or P module tests, were
automatically processed at the E-module first, eliminating the possibility for
carryover to occur for these samples and tests. In the other two (ferritin and
anti_HAV), neither criterion for carryover was met (more than 10% of the
(lower) medical decision level, or exceeding the 2 SD value). According to
investigations of the manufacturer, two additional carry-over sensitive
infectious disease assays were identified: anti-HBs and anti-HBc.Table 3
Sample related carryover withhigh priority test option off. With high priority test option on, sample carryover
cannot occur. (For explanation see results section, sample-related carryover.)
AnalyteExpected values10% of
lower
decision levelLower
detection
limitRatio
high : lowMax. diff
low1–low5(if >2SD)MaterialRelevant Carryover, high
priorityoffRelevant Carryover, high
priorityonAFP<6.2μg/l0.62μg/l0.6μg/l408710.62NativeyesNoCEA<4.6μg/l0.46μg/l0.2μg/l161977.64SpikedyesNoPSA<4μg/l0.4μg/l0.002μg/l7560.20SpikedyesNoFerritin~15–400μg/l1.5μg/l0.5μg/l9692.00SpikednoNoHCG +β<5 mIU/ml0.5 mIU/ml0.1 mIU/ml1170001.30NativeyesNoa-HAV<20 IU/l2.0 IU/l3.0 IU/l11840.25NativenoNoHbsAg<1.0 COI0.1
COI2851060.44nativeyesNo


## 4.4. Workflow

The module combinations (〈PE〉, 〈PPE〉, 〈DPE〉) and test
menu configurations used at the different laboratories were selected to meet
their specific workload demands. An overview is presented in Table 2. To
reflect true routine conditions, the samples were placed on the system in a
sequence mimicking the original arrival pattern in the laboratory, rather than
continuously, to test the system’s potential sample loading capacity. The
resulting cumulative throughput was up to 800 results/hour using 〈PE〉
module combinations and up to 1580 results/hour for 〈PPE〉 module
combinations. A throughput of approximately 2160 results/hour was yielded on
the 〈DPE〉 module combination in laboratory 6. In most of the
laboratories, the number of samples processed was not enough to reach the
system’s maximum throughput capacity.In addition to throughput, we looked carefully at sample processing time
(SPT), the time between sample registration (barcode reading on the instrument)
and the time the last result for that sample is produced. Note that SPT differs
from sample turnaround time (TAT), a commonly used term to describe the time
period from when the samples arrive in the laboratory and the availability of
the last result.The following mean sample processing
times were found for the different sample groups in five laboratories:(i)
13–18 minutes    for samples with general chemistry
requests only
(ISE + P or ISE + P1 + P2),(ii)
22–28 minutes for
samples with immunoassay requests only (E),(iii)
29–38 minutes for
samples with combined requests
(ISE + P + E or ISE + P1 + P2 + E).
The mean SPTs obtained with a 〈DPE〉 combination were comparable:
16 minutes for ISE + D + P, 26 minutes for E, and 27 minutes for ISE + D + P + E.We compared SPT of MODULAR〈PPE〉 with the current six dedicated
routine analysers for a predetermined time period, representing approximately
40% of a day’s workload in laboratory 5. Figure 3 shows that the time to
results for samples with clinical chemistry requests on MODULAR system is
comparable with that of the dedicated routine analysers (mean time 15 minutes,
80th percentile 20 minutes, maximum 38
minutes). Samples with combined requests for both
clinical chemistry and immunochemistry were
processed faster (mean time 34 minutes, 80th percentile 40 minutes, maximum 1 hour)
than on the dedicated analysers (mean time 46 minutes, 80th percentile 58 minutes, maximum 1.8 hours).Figure 3
SPT on
MODULAR system and dedicated routine analysers representing 40% of a daily
routine workload.Depending on test, module and number of
racks waiting in the rerun buffer, rerun results are reported 10–35 minutes after
availability of first results. An example of typical processing times to first
results and to final results (including rerun samples) is shown in Figure4.Figure 4
SPT with
focus on availability of rerun results.MODULAR SWA
supports “reflex
testing,” if the laboratory information system (LIS) offers this functionality.
Frequently practiced for certain indication fields, this feature allows the
automatic request of a further analyte, if a predefined concentration or
concentration range of the originally requested analyte is exceeded. Examples
are as follows: If TSH < 0.27 or > 4.2 mIU/L, FT4 is determined in
addition, if PSA > 4.0μg/L, free PSA is also measured and so on. Even
though it may no longer be as clinically relevant, reflex testing functionality
was assessed using a combination of P-and E-requests: CK → CK-MB(enzymatic) + TnT. The SPT for
such a sample with two additional reflex tests was increased by 30 to 55
minutes (Figure 5).Figure 5
SPT with
focus on reflex testing.Does thesample carry-over setting, which tags the assay in
question automatically as  high priority by the system, influence the
SPT? We compared samples having combined requests (on P- and E-module) with and
without  high priority assays. With  auto rerun off, there was no
result delay. The processing times were increased by 10–15 minutes with  auto
rerun activated, where processing on P module was delayed until final E-module
results were available.Maintenance and troubleshooting are activities which may also
considerably influence the daily workflow. For a modular system, the question
arises whether the entire system or only the affected module is blocked in
order to remedy a problem after, for example, asampling stop alarm.
This type of alarm results in the module discontinuing pipetting of samples.
The different time steps for two such alarms were monitored on a 〈PPE〉
combination at one site. For a provoked tip/vessel pickup-error on the
E-module, the elapsed time from getting the alarm, allowing the module to
finish the tests in process, taking the module down, then fixing the problem,
and getting the module back into operation was a total of 35 minutes; for a
provoked abnormal cap mechanism movement 22 minutes. While the E-module
was unavailable, the ISE and P-modules continued to process samples, and
samples requiring E-module tests were stored in the rerun buffer to be run
automatically when the E-module came back online.An important aspect of instrument consolidation on a single platform is
reduction in personnel hands-on time. In laboratory 5, we compared hands-on
time associated with MODULAR system with that of the 6 existing dedicated
analysers. As shown in Figure6, the operators saved about 10 hours based on
the sample workload; the main contribution was sample handling time. MODULAR
system was operated by 1 technologist while the 6 dedicated analysers required 3
persons.Figure 6
Hands-on
time on MODULAR system compared to dedicated routine analysers representing 40%
of a daily routine workload.One of the participating laboratories (laboratory 1) simulated a
workflow using MODULAR system as a dedicated immunoassay analyser. Tests
included 24 homogeneous tests (10 specific proteins, 6 therapeutic drug tests,
and 8 drugs of abuse tests) on P-module and 18 heterogeneous assays (thyroid,
cardiac, anaemia, and tumour markers) on the E-module, with samples loaded in a
simulated routine-type pattern. The average sample processing times for the
various request patterns were comparable with those mentioned previously
(<35 minutes).


## 4.5. Practicability

With the aid of a questionnaire, the practicability of MODULAR system
was graded as equally good (23% of all scores) or even better (68%) compared to
the evaluators’ currently used routine analysers.


## 5. Discussion

Overall assessment of the experiments can be rated as positive. It was
the first time that there was an opportunity during an evaluation to combine
various laboratory segments with an extensive menu for general chemistry,
specific proteins, drugs, and immunochemistry on one platform.


### 5.1. Imprecision

Since analytical performance was previously verified for the single
MODULAR systems [2, 3], this study did not include extensive analytical performance data.
However, one or two imprecision runs were processed for representative
tests from each analyte group to assure that the system was performing correctly.
Typical within-run CVs of 1 to 3% across the menu of nearly 90 tests were all
within the expected performance and can be rated as excellent. We can emphasize
here that the heterogeneous immunoassays performed with the electrochemiluminescence
technology showed reproducibility similar to the general chemistry tests and
well within clinical demands (see Table 1)
[10–12].


### 5.2. Functionality

The overall low CVs for all analyte groups in the simulated routine
imprecision runs proved that general chemistry and immunochemistry worked very
well together, and, that even under simulatedstress routine conditions,
there was no indication of systematic or random errors. The 6 high CVs of the
routine simulation experiment occurred in only one of 3 runs per laboratory,
and there was no indication that the deviant results were reproducible. The
routine simulation precision experiments demonstrated good performance and full
functionality of the instrument. Because of the sensitivity of the experimental
design, it was possible to identify one severe instrument problem associated
with the E-module masking/unmasking feature during provocation of the analyser.
The error was corrected with a software upgrade and the correct implementation
was confirmed with further routine simulation runs at all sites. Throughout all
other routine environment testing, the instruments reacted correctly based on
the routine simulation data.


### 5.3. Sample Carryover

MODULAR system runs with new user software, combining and unifying the
functionality and features of the single modules and optimizing the processing
of clinical chemistry and immunochemistry requests. For example, sample carryover
to some sensitive immunoassays cannot occur due to intelligent sample processing
whereby samples with requests for carryover sensitive assays, referred to ashigh
priority tests, are processed at the immunology module (E) first. High
priority tests are user-definable and do not delay processing of other
samples, even samples in the same sample rack. As mentioned in the Results section,
processing samples with high priority requests with “Auto-rerun”
activated took 15 minutes longer in comparison to the usual samples. This
however, reduced potential risks and eliminated any manual operator
intervention. If there are only very few specimens with concentrations above
the upper measuring range limit of the high priority tests, the
laboratory manager can decide to deactivate auto-rerun without any high
risk of quality loss but with acceleration of result availability.


### 5.4. Workflow

Workflow depends strongly on the laboratory environment, the sample
loading pattern, and on the MODULAR configuration. Our studies show that
MODULAR system offers the flexibility to fit and meet the requirements of the
individual laboratory. The variations in throughput at the different sites can
be explained by the lab-specific workloads and sample loading patterns.The processing times for the sample groups with general or
immunochemistry requests were similar to those known from the respectivestand-alone modules, thus showing that there was no relevant increase when combining
photometric/ISE and E-modules. In other words, the immunochemistry module did
not slow down the clinical chemistry modules. An average processing time of
approximately 35 minutes for the combined group was rated as being very
acceptable, bearing in mind that those samples were either measured
sequentially on different routine instruments or required additional hands-on
times for splitting/aliquoting in the routine with the current routine
instrumentation. In fact, when these additional times were included, as done in
one laboratory, the mean sample TAT decreased by three hours (from 3.5 to 0.5
hours) using MODULAR system.One laboratory used the〈PE〉 combination for simulating a
dedicated immunoassay analyser covering various laboratory segments. In this
hospital there is a separate sample collection and order process for certain
analytes, which are presently performed on a variety of single analysers.
Therefore, sample splitting is not necessary. The current dedicated analysers
for protein determinations, for drug monitoring or tumour marker measurements
could be replaced by a consolidated workstation, so that only one operator
would be needed to perform these various immunoassays. The laboratory
management assessed a 30 to 50% reduction of manpower for this work on MODULAR
system.During the daily routine, a certain percentage of assays (usually <5%) need a repetition of the analysis, because the measuring range or a defined
repeat limit based on laboratory policy is exceeded. The portion of repeat
measurements due to analytical range limitations on MODULAR system is usually
smaller than 0.5% [2].
MODULAR system offers a user selectable automatic rerun feature,
which can be activated or deactivated for each test.The advantages of automatic rerun—no need for
sample tracking, retrieval, elimination of manual sample predilution, and no
manual reloading—not only increased
safety of results by minimizing possible human error, but also reduced
processing and hands-on times.Also, the fact that MODULAR system supports reflex testing simplifies
the workflow. It is not necessary to wait for the result validation and the
confirmation from the ward to perform the additionalreflex assay. This
is especially important for outpatients since this procedure could avoid a
second hospital visit. Even if samples are held for further tests, reflex
testing is better than the alternatives—measuring for all
tests at the start or manual intervention to locate and transport the samples.
When including the benefits of automatic rerun analysis and reflex testing,
results were available within 30 to 70 minutes.Since the time of this evaluation, the use of MODULAR system has
confirmed this data during a long period of routine work. When comparing the
hands-on times captured at the different sites over one to two days, MODULAR
system yielded a clear advantage. Monitoring over an extended period would be
necessary to obtain more extensive data, but this exceeded the scope of the
study. Nevertheless, it is obvious that there is a potential of saving
personnel capacities since fewer instruments need fewer persons for operation.
MODULAR system requires a skilled operator similar in qualification to that of
the existing analysers compared in this study. However, this person must also
be able to cope with the validation of a large amount of data produced within a
short time or have autoverification available.


### 5.5. Practicability

The practicability of MODULAR system met or exceeded the requirements of
all participating laboratories for 91% of all attributes rated. An opportunity
for improvement was seen in the time required to prepare the analyser for routine
use even though this was one half to three quarters of the time required for
the dedicated routine analysers. Apart from the QC measurements which were
processed directly before routine sampling start, the flexibility of MODULAR
system with background maintenance features allows other tasks to be performed
at any suitable time throughout the shift. Completion of initial QC
measurements for the extended menu processed at the different sites took an
average 30 minutes.The main advantage mentioned by the evaluators was the consolidation
effect resulting in a simplified workflow with a reduction of instruments,
reduced overall processing time, reduced hands-on time, and increased
efficiency without increasing staffing, yet maintaining or even improving
quality.


## 5.1. Imprecision

Since analytical performance was previously verified for the single
MODULAR systems [2, 3], this study did not include extensive analytical performance data.
However, one or two imprecision runs were processed for representative
tests from each analyte group to assure that the system was performing correctly.
Typical within-run CVs of 1 to 3% across the menu of nearly 90 tests were all
within the expected performance and can be rated as excellent. We can emphasize
here that the heterogeneous immunoassays performed with the electrochemiluminescence
technology showed reproducibility similar to the general chemistry tests and
well within clinical demands (see Table 1)
[10–12].


## 5.2. Functionality

The overall low CVs for all analyte groups in the simulated routine
imprecision runs proved that general chemistry and immunochemistry worked very
well together, and, that even under simulatedstress routine conditions,
there was no indication of systematic or random errors. The 6 high CVs of the
routine simulation experiment occurred in only one of 3 runs per laboratory,
and there was no indication that the deviant results were reproducible. The
routine simulation precision experiments demonstrated good performance and full
functionality of the instrument. Because of the sensitivity of the experimental
design, it was possible to identify one severe instrument problem associated
with the E-module masking/unmasking feature during provocation of the analyser.
The error was corrected with a software upgrade and the correct implementation
was confirmed with further routine simulation runs at all sites. Throughout all
other routine environment testing, the instruments reacted correctly based on
the routine simulation data.


## 5.3. Sample Carryover

MODULAR system runs with new user software, combining and unifying the
functionality and features of the single modules and optimizing the processing
of clinical chemistry and immunochemistry requests. For example, sample carryover
to some sensitive immunoassays cannot occur due to intelligent sample processing
whereby samples with requests for carryover sensitive assays, referred to ashigh
priority tests, are processed at the immunology module (E) first. High
priority tests are user-definable and do not delay processing of other
samples, even samples in the same sample rack. As mentioned in the Results section,
processing samples with high priority requests with “Auto-rerun”
activated took 15 minutes longer in comparison to the usual samples. This
however, reduced potential risks and eliminated any manual operator
intervention. If there are only very few specimens with concentrations above
the upper measuring range limit of the high priority tests, the
laboratory manager can decide to deactivate auto-rerun without any high
risk of quality loss but with acceleration of result availability.


## 5.4. Workflow

Workflow depends strongly on the laboratory environment, the sample
loading pattern, and on the MODULAR configuration. Our studies show that
MODULAR system offers the flexibility to fit and meet the requirements of the
individual laboratory. The variations in throughput at the different sites can
be explained by the lab-specific workloads and sample loading patterns.The processing times for the sample groups with general or
immunochemistry requests were similar to those known from the respectivestand-alone modules, thus showing that there was no relevant increase when combining
photometric/ISE and E-modules. In other words, the immunochemistry module did
not slow down the clinical chemistry modules. An average processing time of
approximately 35 minutes for the combined group was rated as being very
acceptable, bearing in mind that those samples were either measured
sequentially on different routine instruments or required additional hands-on
times for splitting/aliquoting in the routine with the current routine
instrumentation. In fact, when these additional times were included, as done in
one laboratory, the mean sample TAT decreased by three hours (from 3.5 to 0.5
hours) using MODULAR system.One laboratory used the〈PE〉 combination for simulating a
dedicated immunoassay analyser covering various laboratory segments. In this
hospital there is a separate sample collection and order process for certain
analytes, which are presently performed on a variety of single analysers.
Therefore, sample splitting is not necessary. The current dedicated analysers
for protein determinations, for drug monitoring or tumour marker measurements
could be replaced by a consolidated workstation, so that only one operator
would be needed to perform these various immunoassays. The laboratory
management assessed a 30 to 50% reduction of manpower for this work on MODULAR
system.During the daily routine, a certain percentage of assays (usually <5%) need a repetition of the analysis, because the measuring range or a defined
repeat limit based on laboratory policy is exceeded. The portion of repeat
measurements due to analytical range limitations on MODULAR system is usually
smaller than 0.5% [2].
MODULAR system offers a user selectable automatic rerun feature,
which can be activated or deactivated for each test.The advantages of automatic rerun—no need for
sample tracking, retrieval, elimination of manual sample predilution, and no
manual reloading—not only increased
safety of results by minimizing possible human error, but also reduced
processing and hands-on times.Also, the fact that MODULAR system supports reflex testing simplifies
the workflow. It is not necessary to wait for the result validation and the
confirmation from the ward to perform the additionalreflex assay. This
is especially important for outpatients since this procedure could avoid a
second hospital visit. Even if samples are held for further tests, reflex
testing is better than the alternatives—measuring for all
tests at the start or manual intervention to locate and transport the samples.
When including the benefits of automatic rerun analysis and reflex testing,
results were available within 30 to 70 minutes.Since the time of this evaluation, the use of MODULAR system has
confirmed this data during a long period of routine work. When comparing the
hands-on times captured at the different sites over one to two days, MODULAR
system yielded a clear advantage. Monitoring over an extended period would be
necessary to obtain more extensive data, but this exceeded the scope of the
study. Nevertheless, it is obvious that there is a potential of saving
personnel capacities since fewer instruments need fewer persons for operation.
MODULAR system requires a skilled operator similar in qualification to that of
the existing analysers compared in this study. However, this person must also
be able to cope with the validation of a large amount of data produced within a
short time or have autoverification available.


## 5.5. Practicability

The practicability of MODULAR system met or exceeded the requirements of
all participating laboratories for 91% of all attributes rated. An opportunity
for improvement was seen in the time required to prepare the analyser for routine
use even though this was one half to three quarters of the time required for
the dedicated routine analysers. Apart from the QC measurements which were
processed directly before routine sampling start, the flexibility of MODULAR
system with background maintenance features allows other tasks to be performed
at any suitable time throughout the shift. Completion of initial QC
measurements for the extended menu processed at the different sites took an
average 30 minutes.The main advantage mentioned by the evaluators was the consolidation
effect resulting in a simplified workflow with a reduction of instruments,
reduced overall processing time, reduced hands-on time, and increased
efficiency without increasing staffing, yet maintaining or even improving
quality.


## 6. Conclusion

Our experience with the MODULARANALYTICS SWA indicates that both
functionally and practically the analyser is a favourable addition to the
clinical laboratory. Each of the various module configurations included in this
study is easily and efficiently managed routine and nonroutine tasks in the
simulated routine scenarios. Overall, samples with combined requests running in
routine workloads, from a menu of about 50 assays, were processed in
approximately 35 minutes; 30 to 70 minutes including reruns and reflex testing.
We saw no negative effects in the quality or timely reporting of test results
when combining general clinical chemistry with heterogeneous immunochemistry
assays on the same analyser. In fact, we found that efficiency was improved, and,
in some cases substantially decreasing sample turn-around time, operator
hands-on time, and personnel, while maintaining or improving the quality of
laboratory processes.



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*Source: 498921-2008-03-31.xml*