UniCel DxI Research Articles

Sources of variation and establishment of Russian reference intervals for major hormones and tumor markers

A multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 22 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population. According to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 758 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 17 hormones and related tests by Beckman Coulter's UniCel DxI 800 immunochemistry analyzer. SVs were explored using multiple regression analysis and ANOVA. Standard deviation ratio (SDR) of 0.4 was used as primary guide for partitioning RIs by gender and age. SDR for between-city difference was <0.4 for all analytes. Secondary exclusion of individuals was done under the following conditions: for female sex-hormones, those with contraceptives (8%); for CA19-9, those supposed to have negative Lewis blood-group (10.5% males and 11.3% females); for insulin, those with BMI≥28 kg/m2 (31%); for the thyroid panel, those with anti-thyroid antibodies (10.3% males; 24.5% females), for CEA those with smoking habit (30% males and 16% females). Gender-specific RIs were required for all analytes except CA19-9, CA15-3, thyroid-related tests, parathyroid hormone, and insulin. Age-specific RIs were required for alpha-fetoprotein, CEA, all sex-hormones for females, FSH and progesterone for both sexes. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol for females in postmenopause, and progesterone for females in premenopause, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit. RIs for major hormones and tumor markers specific for the Russian population were derived based on the up-to-date internationally harmonized protocol by careful consideration of analyte-specific SVs.

Comparison of four routinely used vitamin D automated immunoassays.

BackgroundTo compare four automated immunoassays for the measurement of 25(OH)-vitamin D (25-OHD) and to assess the impact on the results obtained from a healthy population.MethodsWe analysed 100 serum samples on Unicel DxI 800 (Beckman Coulter), Architect i1000 (Abbott), Cobas e411 (Roche) and Liaison XL (DiaSorin). Passing-Bablok regression and Bland-Altman plots were used for method comparison. In order to categorise the obtained values, results were categorised into the following groups: 0-25 nmol/L, 25-50 nmol/L, 50-75 nmol/L and above 75 nmol/L and compared. The percentage of samples below 75 nmol/L, and below 50 nmol/L was then calculated for every method.ResultsAccording to paired comparisons, each method differs from others (p<0.0001) except Cobas vs Architect, which do not show a statistically significant difference (p=0.39). The strongest correlation was found between Liaison and Architect (ρ=0.94, p<0.0001). The percentage of samples below the recommended value of 75 nmol/L were: 70% (Architect), 92% (Liaison), 71% (Cobas) and 89% (Unicel). The percentage of samples below the value of 50 nmol/L were: 17% (Architect), 55% (Liaison), 28% (Cobas) and 47% (Unicel).ConclusionsThe observed differences stem from the use of different analytical systems for 25-OHD concentration analysis and can result in different outcomes. The recommended values should be established for each assay in accordance with the data provided by the manufacturer or in the laboratory, in accordance with proper standardisation.

Comparison of Three Immunoassay Systems for Determining Serum Anti-Mullerian Hormone.

Serum anti-Mullerian hormone (AMH) is a dimeric glycoprotein of the transforming growth factor-β (TGF-β) family of growth and serves as a key biomarker of folliculogenesis as well as steroidogenesis within ovaries. Cobas E601, UniCel DxI 800 and iFlash3000 are automated immunoassay systems which are widely used to measure serum AMH levels in the blood. However, the correlations of serum AMH measured by the three automated immunoassay systems are not well recognized, the aim of this study is to compare the performance of the three automated immunoassay systems and record the correlation of serum AMH concentrations. Serum AMH concentrations were measured in 100 serum samples using the UniCel DxI 800, Cobas E601, and iFlash 3000 automated immunoassay systems on the same day. Passing-Bablok regression analysis and Bland-Altman plot analysis were used to compare the system methods. The concordance correlation coefficient was analyzed to explain interrater agreement between the three immunoassay systems. Bland-Altman plot showed that the concentrations of AMH measured by UniCel DxI 800 were about 0.15 times higher than that measured using Cobas E601, the concentrations of AMH measured by UniCel DxI 800 were about 0.05 times higher than that measured using iFlash 3000, serum AMH concentrations measured by the iFlash3000 were about 0.19 times higher than that measured using Cobas E601. The concordance correlation coefficient ρc was 0.921, 0.909 and 0.978 for the UniCel DxI 800 versus the Cobas E601, the iFlash 3000 versus the UniCel DxI 800, and the iFlash3000 versus the Cobas E601, respectively. The three measurement systems have good correlation with each other for determining serum AMH.

An overlooked situation in the interpretation of serum thyroglobulin level in a papillary thyroid cancer patient

Abstract In the present study we report a case of thyroglobulin (TGB) measurement interference in a total thyroidectomized and radio-ablated 61-year old woman with papillary thyroid cancer. We investigated possible interference in the measurement of TGB due to discordant TGB in relation to clinical condition during the follow-up period. Serum TGB was measured with the chemiluminescence method using Beckman Coulter Unicel DxI 800 instrument. To investigate possible interference in TGB measurement serial dilutions, polyethylene glycol precipitation (PEG), treatment with heterophile blocking tube (HBT), rheumatoid factor level determination and retesting of TGB with an alternative method were performed. Serial dilutions of the serum sample revealed linearity but a remarkable decrease in TGB in the patient’s serum samples post PEG and post HBT treatments. Also, TGB results under functional sensitivity level obtained with a different method suggested that TGB interference developed due to heterophile antibody presence in the serum sample. The patient had unnecessarily undergone expensive imaging techniques, and invasive procedures such as lymph node fine needle aspiration biopsy, before the analytical interference was suspected by the clinician. This report illustrates the importance of early communication and close collaboration between clinicians and laboratorians in order to avoid unnecessary clinical intervention.

The Level of Preoperative Plasma KRAS Mutations and CEA Predict Survival of Patients Undergoing Surgery for Colorectal Cancer Liver Metastases.

Colorectal cancer (CRC) belongs to the most common cancers. The liver is a predominant site of CRC dissemination. Novel biomarkers for predicting the survival of CRC patients with liver metastases (CLM) undergoing metastasectomy are needed. We examined KRAS mutated circulating cell-free tumor DNA (ctDNA) in CLM patients as a prognostic biomarker, independently or in combination with carcinoembryonic antigen (CEA). Thereby, a total of 71 CLM were retrospectively analyzed. Seven KRAS G12/G13 mutations was analyzed by a ddPCR™ KRAS G12/G13 Screening Kit on QX200 Droplet Digital PCR System (Bio-Rad Laboratories, Hercules, CA, USA) in liver metastasis tissue and preoperative and postoperative plasma samples. CEA were determined by an ACCESS CEA assay with the UniCel DxI 800 Instrument (Beckman Coulter, Brea, CA, USA). Tissue KRAS positive liver metastases was detected in 33 of 69 patients (47.8%). Preoperative plasma samples were available in 30 patients and 11 (36.7%) were KRAS positive. The agreement between plasma- and tissue-based KRAS mutation status was 75.9% (22 in 29; kappa 0.529). Patients with high compared to low levels of preoperative plasma KRAS fractional abundance (cut-off 3.33%) experienced shorter overall survival (OS 647 vs. 1392 days, p = 0.003). The combination of high preoperative KRAS fractional abundance and high CEA (cut-off 3.33% and 4.9 µg/L, resp.) best predicted shorter OS (HR 13.638, 95%CI 1.567–118.725) in multivariate analysis also (OS HR 44.877, 95%CI 1.59–1266.479; covariates: extend of liver resection, biological treatment). KRAS mutations are detectable and quantifiable in preoperative plasma cell-free DNA, incompletely overlapping with tissue biopsy. KRAS mutated ctDNA is a prognostic factor for CLM patients undergoing liver metastasectomy. The best prognostic value can be reached by a combination of ctDNA and tumor marker CEA.

Assessment of biotin interference in thyroid function tests.

The aim of the study was to systematically characterize the interference of biotin on thyroid function tests and biotin washout periods.Ten healthy adults were recruited with administration of 5 and 10 mg/d biotin for 7 days. Analyte concentrations of thyroid function tests were measured at baseline prior to starting biotin and from 2 hours to 2 days after withdrawal of 5 and 10 mg/d biotin. The outcomes were compared the baseline with the several points after taking biotin at Roche cobas e602, Beckman UniCel DxI 800, and Abbott Architect 2000 immunoassay platforms, respectively.Ingesting 5 or 10 mg/d of biotin for 7 days could produce positive or negative interference among the thyroid function tests at Roche cobas e602 and Beckman UniCel DxI 800 systems, but no interference on Abbott Architect 2000. Interference duration of 5 mg/d biotin for Roche cobas e602 and Beckman UniCel DxI 800 of thyroid function tests lasted for 8 hours, while 10 mg/d biotin interfered with Roche cobas e602 or Beckman UniCel DxI 800 for 1 day or 2 days.This study provides valuable guidance on biotin washout periods at doses common in over-the-counter supplements necessary to avoid false assay results.Trial registration: ChiCTR1800020472.

Routine free thyroxine reference intervals are suboptimal for monitoring children on thyroxine replacement therapy and target intervals need to be assay-specific

Central hypothyroidism is a condition where there is (qualitatively or quantitatively) TSH deficiency, leading to reduced thyroid hormone production. In such patients, serum TSH does not accurately reflect the adequacy of thyroxine replacement, as the log-linear relationship between thyrotropin (TSH) and free thyroxine (FT4) is lost. We aimed to prospectively determine the optimal physiological FT4 treatment range for children treated for primary hypothyroidism, based on their serum TSH concentrations. This information could be used to guide optimal therapy for all children on thyroxine replacement, including those with central hypothyroidism. In total, sixty children (median age: 11 years, range: 11 months to 18 years) were recruited over 21 months. They were prescribed a stable dose of thyroxine for at least 6–8 weeks prior to a thyroid function test that consisted of serum TSH, FT4 and free triiodothyronine (FT3) measurements. The serum sample for the thyroid function tests was collected before ingestion of the daily dose, i.e. the trough concentration, and measured using Beckman Coulter UniCel DxI 800 instrument, Siemens Advia Centaur, Roche Cobas, Abbott Architect, Ortho Clinical Diagnostics Vitros 5600 (Ortho-Clinical Diagnostics, Raritan, NJ) platforms. The FT4 and FT3 reference intervals showed significant inter-method difference. The lower limit of the FT4 reference intervals were generally shifted mildly higher when the TSH concentration of the children were restricted from 0.5–5.0 mIU/L to 0.5–2.5 mIU/L. By contrast, the upper limit of the FT3 and FT4 reference intervals were relatively stable for the different TSH concentrations. Assay-specific target ranges for optimal thyroxine therapy are required until FT4 assay standardisation is realised.

Performance Evaluation of CEA Assay on Beckman Coulter UniCel DxI 800

Abstract Carcinoembryonic antigen (CEA) is a glycoprotein normally found in embryonic entodermal epithelium. Increased levels may be found in patients with primary colorectal cancer or other malignancies. CEA levels are not useful in screening the general population for undetected cancers. However, CEA levels provide important information about patient prognosis, recurrence of tumors after surgical removal, and effectiveness of therapy. The aim of this study was to assess the analytical performance of CEA assay on a Beckman Coulter UniCel DxI 800. The linearity, sensitivity, reference range, precision, and accuracy were evaluated following CLSI guidelines. The within-run and between-run precisions were assessed by analyzing QC material at low and high levels of concentrations. The accuracy was assessed by comparison of 152 patient serum CEA on DXI with CEA on a previously established ADVIA Centaur System. The analytical measurement range was determined to be linear between 0.00 and 951.3 ng/mL with a slope of 0.976 and intercept of 0.075. The limit of blank (LOB) was determined as 0.03 ng/mL and the limit of detection (LOD) was 0.1 ng/mL. The reference range was verified as 0.0 to 3.0 ng/mL (nonsmokers) and 0.0 to 5.0 ng/mL (smokers). The within-run CVs for CEA were 4.4% at the low level of 2.239 ng/mL and 2.5% at the high level of 38.1 ng/mL. The between-run CVs at low and high levels were 4.4%, and 4.0%, respectively. Comparison of CEA on the Beckman Coulter UniCel DxI 800 with CEA on the ADVIA Centaur System of 152 patient samples showed the slope was 1.541 (95% CI, 1.515-1.567) with an intercept of 0.17 and a correlation coefficient of 0.9943 (Deming). The mean bias between Beckman and ADVIA was 6.49 (41.71%). In summary, our data demonstrate that CEA assay on the Beckman Coulter UniCel DxI 800 has good linearity and precision. There is also good correlation between CEA tested on the Beckman Coulter UniCel DxI 800 and on the ADVIA Centaur System with a positive bias.

Verification of Access GI Monitor (CA 19-9) Assay on Beckman Coulter Unicel DXI 800

Abstract CA 19-9 antigen has been identified in patients with colorectal, pancreatic, bile duct, hepatocellular, stomach, and esophageal cancers. Noncancerous conditions that may elevate CA 19-9 levels include cirrhosis, cholangitis, hepatitis, pancreatitis, and nonmalignant gastrointestinal diseases. CA 19-9 antigen levels may be used as an aid in monitoring response to therapy or disease progression in cancer patients. The objective of this study was to assess the analytical performance of the Access GI Monitor assay on Beckman Coulter UniCel DXI 800. CA 19-9 was quantitatively determined on the Beckman Coulter UniCel DXI 800 following CLSI guidelines. The performance was evaluated for linearity, sensitivity, reference range, and precision. The within-run and between-run precisions were assessed by analyzing QC material at low and high levels of concentrations. Accuracy was assessed by comparison with the previously established Siemens ADVIA Centaur XP. Antigen level values were classified as positive or negative based on the upper limit of the reference range to assess concordance between the two analyzers. The accuracy of each analyzer was also assessed by correlating the discordant antigen values with the patients’ clinical history. For the Beckman Coulter DXI assay, the analytic measurement range was determined to be linear between 0.8 and 2,000 U/mL with a slope of 1.018 and intercept of 4.13. The limit of blank was determined as 0.09 U/mL. The reference range was verified as 0 to 35 U/mL. The within-run CVs for CA 19-9 were 3.7% at both the low level of 23.54 U/mL and high level of 262.56 U/mL. The between-run CVs at low and high levels were 4.34% and 6.36%, respectively. A total of 327 patient samples were analyzed in the comparison of CA 19-9 levels on Beckman Coulter DXI and Siemens ADVIA Centaur XP. On Deming regression, the slope was 0.665 with an intercept of 136.4 and correlation coefficient of 0.8964; there was wide scatter between the two methods. The mean bias between the two analyzers was –291.1 (–22.8%). The correlation coefficient was 0.8931, and the bias was –770.7 (–26.1%) when both were positive. The correlation coefficient was 0.7949, and the bias was –0.8 (–6.1%) when both were negative. The agreement of the two methods was 91% (n = 298) and disagreement was 9% (n = 29). After clinical analysis of 18 discordant values, six data points correlated better with the Siemens Centaur XP and the remaining 12 correlated better with the Beckman Coulter DXI. Our data demonstrate that CA 19-9 on Beckman Coulter DXI has good linearity and precision. There is poor to fair correlation between the two methods. Agreement based on clinical classification of positive and negative results is good. The Beckman Coulter DXI correlates with the patient clinical history better than the Siemens Centaur XP when comparing discordant values between the analyzers.

Establishment of reference intervals for thyroid hormones in premature infants beyond the first week of life using Beckman Coulter Unicel DxI 800

BackgroundThis 4-year retrospective cohort study aimed to establish reference intervals for free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) in premature infants using the Beckman Coulter Unicel DxI 800 automated immunoassay system. MethodsStudy subjects included 605 preterm infants with a gestational age of 26–36 weeks (corrected: 29–38 weeks). Pearson correlation was used to evaluate the association between hormone levels and gestational and corrected gestational ages. A nonparametric method was used to establish reference intervals based on corrected gestational age. ResultsFT3 and FT4 levels were positively correlated with gestational and corrected gestational ages, respectively. TSH levels were slightly negatively correlated with gestational and corrected gestational ages. FT3 significantly differed according to corrected gestational age (29–33 weeks vs 34–38 weeks); however, the difference was smaller than the reference change value (RCV) for the FT3 test. Thus, we combined the FT3 reference intervals into a single reference interval: 2.65–4.93 pmol/L (29–38 weeks). The reference intervals of FT4 and TSH were 11.20–24.97 pmol/L (29–38 weeks) and 1.01–10.14 mIU/L (29–38 weeks), respectively. ConclusionsUnlike those of full-term infants or adults, the reference intervals established in this study are applicable in premature infants. These results highlight the importance and complexity of establishing instrument-specific thyroid hormone reference intervals for preterm infants.

Detection and characterization of estradiol (E2) and unconjugated estriol (uE3) immunoassay interference due to anti-bovine alkaline phosphatase (ALP) antibodies

ObjectivesCompetitive immunoenyzmatic assays for estradiol (E2) and unconjugated estriol (uE3) on UniCel DxI 800 Access immunoassay systems (Beckman Coulter) utilize bovine alkaline phosphatase (ALP) for amplification. In these assays, rare ‘IND’ error flags indicate that a relative light unit (RLU) raw result is past the high or low end of the calibration curve but cannot be differentiated from an instrument error or analytical interference. The present studies were conducted to establish a protocol to identify analytical interference and to characterize its mechanism when present. Design and methodsMatrix and recovery studies were conducted to establish a protocol for interference identification. Spiking experiments with inactivated calf intestinal ALP were performed to determine whether interference could be blocked. Commercial anti-ALP antibodies (Abs) were spiked into human serum to model assay interference. Three E2 immunoassays which do not include ALP as a reagent component (cobas e602, Roche; Centaur XP, Siemens; ARCHITECT i2000SR, Abbott) were tested for comparative purposes. Results1:2 dilution of specimen into Access Sample Diluent A (Beckman) differentiated IND error flags due to true low results (e.g. less than the analytical measurement range; AMR) from those due to assay interference. Interferences were reduced by pre-incubation with inactivated ALP and could be replicated by spiking with commercial anti-ALP Abs. ConclusionsPatient anti-bovine ALP Abs can cause interference on DxI 800 E2 and uE3 assays. This model can be used to investigate interference risk with other ALP-dependent assays.

Establishing sex-specific reference interval for the Beckman Coulter UniCel DxI 800 TSH (3rd IS) in Chinese euthyroid population based on a multicenter study

Ultra-high pressure (UHP) waterjet cutting technology is used across a multitude of industries. An agricultural application recently developed by the South Australian No-Till Farmers Association consists of an innovative crop residue cutting ‘liquid coulter’ - known as Aqua-Till®. The wheat straw stem cutting capacity of the device was evaluated under controlled laboratory conditions at the University of South Australia, using a purpose-made straw holding tray moving at a controlled speed under the path of a stationary UHP nozzle. The impacts of technology settings and straw conditions were measured. The cutting performance was assessed based on the degree of fully cut straw stems, integrating the extent of partially cut stems, from a quantity calibrated to an equivalent dry stem load in Mg/ha. Results showed that when operated at 380 MPa pressure, the device delivered very high cutting capacity of wheat straw stems of 10−35 Mg/ha across the range of nozzle orifice diameters (0.15-0.3 mm) and forward speeds (6−12 km/h) tested. The UHP waterjet cutting unit was found to operate most effectively when the residue was wet and placed under compression. Halving travel speed increased the cutting capacity by an average 12 % indicating a non-linear impact of speed. No effect of nozzle to target distance could be detected over the 5−70 mm range tested. The cutting performance of wet, compressed residue was mapped against the water volume rate required over a range of speeds and orifice diameters. Correction factors for extending cutting performance estimations to dry and/or loose residue conditions were also determined. Across the range of nozzle orifice diameters and speeds investigated, the laboratory data for wet compressed residue indicate that a nominal 150 L/ha volume of water, deemed acceptable under Australian dryland cropping conditions, could provide straw stem cutting capacities of up to 12.5 Mg/ha, 19 Mg/ha and 35 Mg/ha at 300 mm, 500 mm and 1000 mm nozzle row spacing, respectively, at a nominal 380 MPa operating pressure. In this study, the waterjet technology demonstrated very effective residue cutting, which could be maximised under specific residue conditions and technology settings. The results indicate that the technology could become an effective tool for assisting residue handling in no-till planting applications, particularly in wet stubble and soft soil environments where traditional mechanical coulters fail. Further research is required to develop accurate operational guidelines for a range of field residue type and conditions, as well as clarify the technology cost-effectiveness in order to facilitate adoption within the no-till cropping industry.

Assessment of Access hsTnI 99th percentiles upper reference limits following IFCC recommendations

BackgroundThe detection of an increase and/or decrease of cardiac troponin (cTnI) values, with at least one value above the 99th percentile of the upper reference limit (URL) have a central role in acute myocardial infarction (AMI) diagnosis. The employment of sex specific 99th percentile URLs and High-sensitivity (Hs) assays are recommended. We assessed sex specific 99th percentile URL for Access Hs-cTnI and AccuTnI3+ (Beckman Coulter) using European donor reference population following recent International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations. Methods300 males and 300 females plasma samples were collected. Both chemiluminescent immunoenzymatic assays were performed on UniCel DxI 800 platform (Beckman Coulter). ResultsFor Access hsTnI, the observed sex-specific 99th percentile URLs were 5.5 (90% CI: 4.4–7.6) for females and 13.9 ng/L (90% CI: 7.4–17.4) for males. For AccuTnI+3 we could not establish them because the assay couldn't report detectable values of troponin for most of the analyzed samples. ConclusionThe sex-specific 99th percentile URLs established for Access hsTnI assay were significantly lower than those declared by the manufacturer caused by the different choice of population selection, age groups and sample types: for those reasons, we maintain the 99th URLs provided by manufacturer.

Vitamin D status in pregnant women visiting a tertiary care center of North Eastern India.

Background:Studies of vitamin D (VD) physiology suggest that effects of vitamin D deficiency (VDD) could be much broader than rickets including cardiovascular disease, cancers, diabetes, infection, and allergy and pregnancy complications. Data regarding the prevalence of hypovitaminosis in pregnancy are scanty especially in north eastern part of India. Therefore, this study has undertaken with the intention to find out prevalence and outcome of hypovitaminosis of VD in pregnancy.Materials and Method:In total, 177 pregnant women with singleton pregnancy, <16 weeks of gestational age, visited to antenatal clinic of our institute were consecutively enrolled for the study. The serum VD was estimated by Beckman coulter unicel DXI immunoassay system using the principle of Chemiluminescence. Incidence of vitamin deficiency and insufficiency calculated. VDD was defined as 25(OH)D levels in blood <20 ng/mL, and insufficiency of VD was defined as 25(OH)D levels <32 ng/mL. Antenatal complications, such as intrauterine growth restriction (IUGR), oligohydramnios, pre-eclampsia, preterm labor, gestational diabetes, if any, were noted. Labor and delivery information including induction of labor, mode of delivery, and newborn birth weight were noted.Result:In total, 177 women recruited for the study. Mean age and parity of the subjects were 26.71 ± 9.96 and 2.10 ± 1.8, respectively. For detailed statistical analysis, women were divided into three groups depending upon their VD levels: deficiency group [25(OH)D level <20 ng/mL], insufficiency group [25(OH)D level <32 ng/mL], and sufficient group [25(OH)D level >32 ng/mL]. VDD was present in 84.18% subjects. VD insufficiency was present in 12.44% of cases. There is association of preeclampsia, cesarean section, and low birth weight babies with lower level of VD.Conclusion:This study showed that the prevalence of VDD in pregnancy is astonishingly high till now there is no guideline to screen antenatal women for VDD. As the test is costly even, offering it to all at-risk women may not be cost effective compared with offering universal supplementation, particularly as treatment is regarded as being very safe.

Evaluation of the analytical performance of the Beckman Coulter Unicel DXI 800 Access Total 25(OH) Vitamin D immunoassay

AbstractBackgroundAs vitamin D has recently been implicated in various diseases, vitamin D testing has gained a lot more significance. Vitamin D deficiency is quite prevalent, and detection of this condition is important. Several manufacturers have developed new automated immunoassays for this purpose. In this study, we aimed to evaluate the analytical performance of the Access Total 25(OH) Vitamin D immunoassay on the Beckman Coulter Unicel DXI 800 analyzer, through comparison with the reference method, liquid chromatography/tandem mass spectrometry (LC-MS/MS).MethodsThe study was conducted with 148 patient samples which were sent to Ankara Numune Training and Research Hospital for routine vitamin D testing. Every sample was analyzed with both Unicel DXI 800 immunoassay analyzer and LC-MS/MS. The concordance of the results was evaluated with Passing-Bablok regression analysis and Bland-Altman plot. Additionally, imprecision, interference, limit of blank (LOB), recovery, linearity and carry-over studies were performed for the Beckman Coulter Unicel DXI 800 analyzer.ResultsWhen compared to LC-MS/MS, the Access Total 25(OH) Vitamin D immunoassay on the Beckman Coulter Unicel DXI 800 analyzer had an R-value of 0.957 (intercept: −3.938, slope: 1.185) and a mean bias of 9.5%. The concordance correlation coefficient (CCC) between the two methods was 0.916. The intra-assay, inter-assay and total coefficient of variation (CV%) for the Unicel DXI 800 vitamin D immunoassay were 3.3%, 5.3% and 8.3%, respectively, at 31.7 ng/mL concentration, and 2.1%, 3.2% and 7%, respectively, at 66.8 ng/mL concentration.ConclusionsThe Access Total 25(OH) Vitamin D immunoassay method has acceptable analytical performance, and the results are in concordance with the LC-MS/MS results.

Characterization of bilirubin interference in three commonly used digoxin assays

BackgroundDue to the narrow therapeutic range of digoxin, determining serum/plasma digoxin concentrations is critical for assessing patients with congestive heart failure, atrial fibrillation, and certain types of arrhythmias. However, digoxin quantification by competitive immunoassays is susceptible to interferences that may alter the accuracy of its measurement in patient plasma. This study aimed to characterize the extent of bilirubin interference in three commonly used digoxin immunoassays. MethodsDigoxin concentrations were compared using the Beckman Coulter® Unicel DxI 800, the Vitros® 4600, and the Roche Cobas® 8000 in neat or digoxin-spiked icteric and non-icetric plasma samples. A mixing study was performed to demonstrate how digoxin quantification is affected by bilirubin. An equation was derived that predicts the response of the DxI 800, given known bilirubin and digoxin concentrations. ResultsThe DxI reported detectable concentrations of digoxin in high bilirubin samples with no added digoxin, while the Vitros® 4600 and Cobas® 8000 gave virtually undetectable results. Spiking digoxin into samples with elevated bilirubin concentrations resulted in a higher percent recovery for the DxI 800 when compared to the other two platforms. The mixing study also revealed an increase in the percent recovery in the DxI 800, while the Vitros® 4600 and Cobas® 8000 were comparable to the expected concentration of digoxin. ConclusionsThe DxI 800 is most prone to interference by bilirubin, while the Vitros® 4600 and Cobas® 8000 are relatively unaffected. Icteric samples should be interpreted with caution if digoxin quantification is needed, especially on the DxI 800 assay.

Different Strategy Between Roche Cobas e System and Beckman Coulter UniCel DxI System to Resolving High-Dose Hook Effect for Quantitative Alpha Fetoprotein Analysis

Different Strategy Between Roche Cobas e System and Beckman Coulter UniCel DxI System to Resolving High-Dose Hook Effect for Quantitative Alpha Fetoprotein Analysis

A multicenter study for the evaluation of the reference interval for TSH in Italy (ELAS TSH Italian Study)

Background The aims of this study were: (1) to calculate reliable thyroid stimulating hormone (TSH) reference intervals using laboratory databases; (2) to evaluate the relationship between TSH, sex and age values in different large Italian populations. Methods The TSH values stored in the laboratory information system of clinical laboratories of four Italian city hospitals, including 146,801 TSH measurements (with the respective age and sex data of individuals) were taken in consideration. Assuming a log-normal distribution, to log-transformed TSH values were applied the Dixon's iterative principle in order to exclude the outliers. At the end of this iterative process 142,821 log-transformed TSH results remained. The four clinical laboratories measured serum TSH concentrations using the same TSH immunoassay method (Access TSH 3rd IS, using UniCel DxI platform). Results The TSH reference interval calculated in the present study (0.362-5.280 mIU/L) is similar to that suggested by the manufacturer for the Access TSH 3rd IS assay (0.45-5.33 mIU/L). TSH values in females were significantly higher than in males (females: mean=2.06 mIU/L; standard deviation [SD]=1.26 mIU/L; n=101,243; males: mean=1.92 mIU/L; SD=1.19 mIU/L; n=41,578; p<0.0001). Moreover, a negative linear relationship was observed between TSH throughout all interval age values (from 0 to 105 years). Conclusions The results of the present multicenter study confirm that data mining techniques can be used to calculate clinically useful reference intervals for TSH. From a pathophysiological point of view, our results suggest that some Northern populations of Italy might still suffer some harmful effects on the thyroid gland due to mild to moderate iodine intake deficiency. Specific clinical trials are needed to confirm these results.

Alpha-fetoprotein in pericardial, peritoneal, and pleural fluids: A body fluid matrix evaluation

ObjectivesAlpha-fetoprotein (AFP) measurement in pericardial, peritoneal (ascites), and pleural fluids is sometimes requested by clinicians as supportive evidence in the evaluation of suspected malignancy. As commercially available, Food and Drug Administration (FDA)-cleared AFP assays are not validated for these fluid types, laboratories must complete additional validation studies to comply with regulatory requirements for body fluid testing. The objective of this study was therefore to conduct a matrix evaluation for these body fluid types using the Beckman Access AFP assay on the UniCel DxI 800 immunoassay system. Design and methodsUsing an Institutional Review Board (IRB) approved protocol, previously collected pericardial fluid, peritoneal fluid, pleural fluid, and serum specimens were de-identified and frozen at −20 °C prior to matrix evaluation experiments. Spiked recovery, mixed recovery/linearity, and precision studies were conducted. ResultsIn spiked and mixed recovery studies, the average percent (%) recovery was within predefined acceptable limits (±15%) for all three body fluids. Linearity was observed over the analytical measurement range (AMR) for all three body fluids (slope, intercept, systematic error): pericardial 0.988, −0.1, 6.1%; peritoneal 0.986, 0.0, 4.1%; and pleural 1.016, 0.0, 1.6%. Imprecision was ≤6.0% CV for all three body fluids at both high and low AFP concentrations. ConclusionsMatrix interference with AFP testing was not observed for pericardial, peritoneal, or pleural fluids on the Beckman UniCel DxI 800 system.

Performance characteristics of the Beckman Coulter UniCel DxI 800 TSH (3rd IS) assay

IntroductionBeckman Coulter recently reformulated their commercial TSH assay with primary calibration to the World Health Organization 3rd TSH international standard. An extensive evaluation of the performance characteristics for this assay was completed. MethodsIntra-day and inter-day precision was evaluated using 3 concentrations of commercial quality control material. Linearity, reportable range, stability, sensitivity and susceptibility to common inferences were determined using pooled patient specimens. Inter-assay variability was assessed across 5 different platforms (n=47 patient specimens). ResultsIntra-day and inter-day CVs were <10% at all concentrations evaluated. The LOQ, LOD and LOB were 0.0047μIU/ml (10% CV), 0.0012μIU/ml and 0.0005μIU/ml, respectively. Variable bias was observed for the TSH3 assay when evaluated against the previous generation assay and other platforms, but overall TSH3 gave comparable results. ConclusionsThe TSH3 assay for UniCel DxI 800, is precise, highly sensitive and comparable to the previous generation assay. The assay is acceptable for clinical testing.