Prediction of the need for phototherapy during hospital stay in preterm infants by transcutaneous bilirubinometry.

BACKGROUND: Neonatal hyperbilirubinemia is a common condition that frequently requires treatment with phototherapy and less commonly by exchange transfusion, especially in preterm infants. It is important to identify and monitor infants at risk of severe unconjugated hyperbilirubinemia early in the postnatal period to instigate appropriate management plans. AIMS: To evaluate transcutaneous bilirubinometry (TCB) as a screening tool at 24 and 48 h of age to predict the need for phototherapy during hospital stay in preterm infants. STUDY DESIGN: A single centre prospective cohort study in a level III perinatal centre. SUBJECTS: Preterm infants (23+0 to 36+6 weeks of gestation) were eligible for enrolment. OUTCOME MEASURES: Primary outcome was to assess the predictive value of TCB at 24 and 48 h of age for the need of phototherapy during hospital stay. RESULTS: A total of 338 preterm infants were enrolled. The majority of infants (98.1%) born below 32 weeks of gestation required phototherapy. For infants born at >31 + 6 weeks of gestation, TCB at 24 h of age ≥81 µmol/l had sensitivity 83%, specificity 56%, positive predictive value (PPV) 54.7% and negative predictive value (NPV) 84%. TCB at 48 h of age ≥145 µmol/l had sensitivity 65%, specificity 62%, PPV 24% and NPV 90%. CONCLUSION: TCB performed poorly at 24 and 48 h of age as a predictor of phototherapy during hospital stay in preterm infants. The negative predictive value of the test at 48 h of age might be helpful for infants born after 31 + 6 weeks of gestation.

Safety of a continuous glucose monitoring device during hyperbaric exposure.

Background: Hyperbaric oxygen therapy has been demonstrated to lower blood glucose levels in patients with diabetes. Continuous glucose monitoring (CGM) allows glucose monitoring in real time. Battery-operated CGM transmitters have yet to be formally tested and given safety approval for use in a hyperbaric environment. Materials and Methods: We evaluated and tested commercially available Dexcom® G6 CGM transmitters under hyperbaric conditions. Each transmitter contains a 3V, 130-mAh (0.39 Wh) lithium manganese dioxide battery (IEC CR1632) and circuit board that are fully encapsulated in epoxy. Each transmitter is pressurized to 90 pounds per square inch (psi) in an autoclave at 40°C for up to 72 hours during manufacturing to ensure that all enclosed air spaces are eliminated from the epoxy. We compared the CGM components against section 14.2.9.3.17.5 of the 2018 National Fire Protection Association 99 (NFPA 99) Health Care Facilities Code requirements. Six CGM transmitters attached to estimated glucose value generators (EGVGs) underwent 11 pressurization cycles to 45 feet of seawater (fsw). All transmitters were returned to the manufacturer to assess post-exposure structural integrity. G6 sensors, which contain no electrical components or compressible air spaces, do not pose a risk in the hyperbaric environment. Results: There was no observed change in preset EGVG readings during hyperbaric exposures. Post-exposure testing revealed no structural compromise after repeated hyperbaric exposures. Conclusions: The CGM transmitter meets section 14.2.9.3.17.5 of the 2018 NFPA 99 requirements for battery-operated devices allowed for use in a hyperbaric environment. This analysis revealed no significant safety concerns with subjecting Dexcom G6 CGM transmitters to hyperbaric environments.

Alanine Aminotransferase Results Differ by Analyzer Manufacturer in a National Integrated Health Setting, 2012-2017.

CONTEXT.­: Disease guidelines specify universal alanine aminotransferase (ALT) thresholds for clinical decision-making, yet the effect of variability among ALT analyzers remains unclear. OBJECTIVE.­: To compare ALT results from different analyzers from 2012-2017. DESIGN.­: Veterans Health Administration (VHA) laboratories perform external ALT proficiency testing using standardized College of American Pathologists (CAP) samples in analyzers by 5 manufacturers. In this operational analysis, we evaluated 22 950 ALT values from 80 independent CAP samples tested at 223 laboratories. Using mixed effects modeling, we estimated the association between analyzer manufacturer and CAP outcome, adjusting for manufacturer, facility, and calendar year. We performed subgroup analyses on CAP samples with overall means near clinical guideline-specified thresholds, including less than 50 U/L (n = 10) and less than 35 U/L (n = 5). RESULTS.­: The VHA used Abbott Laboratories (n = 3175; 14%), Beckman Coulter Diagnostics (n = 8723; 38%), Roche Diagnostics (n = 2595; 11%), Siemens Healthineers USA (n = 5713; 25%), and Vitros/Ortho Clinical Diagnostics (n = 2744; 12%) analyzers. The CAP samples (n = 80 samples, n = 22 950 tests) covered a wide range of mean ALT values (21-268 U/L). The average difference in mean ALT value per sample between the highest-reading and lowest-reading manufacturers was 15.4 U/L (SD = 1.8) for the 10 samples with mean ALT less than 50 U/L, and it was 10.4 U/L (SD = 3.6) overall (n = 80). In linear mixed effects modeling, we found statistically significant differences in ALT values between the different manufacturers in each year. CONCLUSIONS.­: We found statistically and clinically meaningful differences between analyzers across the ALT spectrum in each year, including at ALT levels lower than 50 U/L and lower than 35 U/L. Universal ALT thresholds should be avoided as a trigger for clinical action until differences between analyzers can be resolved.

PAIRED BIOCHEMICAL ANALYSIS OF PIGMENTED PLASMA SAMPLES FROM ZOO-KEPT AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER) USING A POINT-OF-CARE AND A STANDARD WET CHEMISTRY ANALYZER.

American flamingos (Phoenicopterus ruber) are commonly kept in zoological collections, making health monitoring essential. Use of point-of-care (POC) blood analyzers that require small volumes of whole blood samples produces prompt results allowing for rapid clinical decision-making. To evaluate and compare blood biochemistry analysis results analyzed by a POC biochemistry analyzer and a laboratory wet biochemistry analyzer, blood was collected from 17 apparently healthy zoo-kept American flamingos. Analyzer agreement was investigated using the Passing-Bablock regression analysis and Spearman correlation coefficients. Plasma samples from all birds were bright yellow in color. The results from the POC analyzer used in this study were found to be outside acceptance and clinical allowable error limits when compared with the laboratory analyzer for phosphorus (Phos), total protein (TP), albumin (Alb), glucose (Glu), creatine kinase (CK), and potassium (K). For aspartate aminotransferase (AST), results were within clinical allowable error but outside the acceptance limits, and for calcium (Ca) and sodium (Na), results were within both limits. The POC analyzer failed to measure the uric acid (UA) concentrations of all the samples, and reported all bile acids (BA) concentrations as below its minimal measurable limit. The use of analyzer-specific reference intervals is recommended for most analytes tested. The POC analyzer used in this study cannot be recommended for measuring UA concentrations in brightly colored samples from American flamingos.

Optoacoustic diagnostic modality: from idea to clinical studies with highly compact laser diode-based systems.

Optoacoustic (photoacoustic) diagnostic modality is a technique that combines high optical contrast and ultrasound spatial resolution. We proposed using the optoacoustic technique for a number of applications, including cancer detection, monitoring of thermotherapy (hyperthermia, coagulation, and freezing), monitoring of cerebral blood oxygenation in patients with traumatic brain injury, neonatal patients, fetuses during late-stage labor, central venous oxygenation monitoring, and total hemoglobin concentration monitoring as well as hematoma detection and characterization. We developed and built optical parametric oscillator-based systems and multiwavelength, fiber-coupled highly compact, laser diode-based systems for optoacoustic imaging, monitoring, and sensing. To provide sufficient output pulse energy, a specially designed fiber-optic system was built and incorporated in ultrasensitive, wideband optoacoustic probes. We performed preclinical and clinical tests of the systems and the optoacoustic probes in backward mode for most of the applications and in forward mode for the breast cancer and cerebral applications. The high pulse energy and repetition rate allowed for rapid data acquisition with high signal-to-noise ratio from cerebral blood vessels, such as the superior sagittal sinus, central veins, and peripheral veins and arteries, as well as from intracranial hematomas. The optoacoustic systems were capable of automatic, real-time, continuous measurements of blood oxygenation in these blood vessels.

Validation of a hand-held point of care device for lactate in adult and pediatric patients using traditional and locally-smoothed median and maximum absolute difference curves.

BACKGROUND: Lactate is commonly used in septic patients and is a viable biomarker for trauma patients. Its pre-hospital use could assist triaging and managing patients with these conditions. METHODS: We evaluated the analytical performance of the point-of-care (POC) StatStrip Xpress Lactate Meter (Nova Biomedical) and compared it to the ABL 800 (Radiometer). We measured lactate in 250 adult and 250 pediatric whole blood samples in 2 laboratories. The performance of the POC meter was assessed by traditional linear regression and Bland-Altman plots, and locally-smoothed (LS) median absolute difference and maximum absolute difference (MAD and MaxAD) curves. RESULTS: The StatStrip was linear with acceptable reproducibility at clinically relevant concentrations. Correlation with the ABL800 showed a negative bias for both populations with slope, bias ±SD (% bias) of 0.78, -0.4±0.7 (-14.5%) in children and 0.80-0.3±0.6 (-13.3%) in adults. The proportional bias appeared more significant at concentrations >4mmol/l (36.0mg/dl). The StatStrip misclassified 7.6 and 8.8% pediatric and adult samples, respectively, to lower risk categories defined using guidelines driven cut-offs. The LS MAD curves identified one breakout, concentration where the LS MAD exceeds the total allowable error limit of 0.3mmol/l (2.7mg/dl), at lactate concentrations of 3.8 and 3.2mmol/l (34.2 and 28.8mg/dl) in the pediatric and adult curves, respectively. Breakthroughs, points at which the LS MaxAD curve exceeds the 95th percentile of MaxADs, occur at concentrations above 7.5mmol/l (67.6mg/dl) for both populations where the performance of the POC meter became erratic. We concluded that if serial lactate measurements are performed, the same method should be used for baseline and follow up measurements. The LS MAD and LS MaxAD curves allowed visual and quantitative mapping of the performance of the lactate POC meter over the range of concentrations measured. CONCLUSIONS: This approach seems useful for the identification of points at which the performance of a POC meter differs significantly from a comparison method and thresholds of poor analytical performance.

Detecting paraprotein interference on a direct bilirubin assay by reviewing the photometric reaction data.

BACKGROUND: The direct bilirubin (D-Bil) assay on the AU Beckman Coulter instrumentation can be interfered by paraproteins, which may result in spurious D-Bil results. In a previous work, we took advantage of this fact to detect this interference, thus helping with the identification of patients with unsuspected monoclonal gammopathies. In this work, we investigate the possibility to detect interference based on the review of the photometric reactions, regardless of the D-Bil result. METHODS: The D-Bil assay was carried out in a set of 2164 samples. It included a group of 164 samples with paraproteins (67 of which caused interference on the assay), as well as different groups of samples for which high absorbance background readings could also be expected (i.e. hemolyzed, lipemic, or icteric samples). Photometric reaction data were reviewed and receiver operating characteristics (ROC) curves were used to establish a cut-off for absorbance that best discriminates interference. RESULTS: The best cut-off was 0.0100 for the absorbance at the first photometric point of the complementary wavelength in the blank cuvette. Once the optimal cut-off for probable interference was selected, all samples analyzed in our laboratory that provided absorbance values above this cut-off were further investigated to try to discover paraproteins. During a period of 6 months, we detected 44 samples containing paraproteins, five of which belonged to patients with non-diagnosed monoclonal gammopathies. CONCLUSIONS: Review of the photometric reaction data permits the systematic detection of paraprotein interference on the D-Bil AU assay, even for samples for which reasonable results are obtained.

Utility of Decision Rules for Transcutaneous Bilirubin Measurements.

BACKGROUND: Transcutaneous bilirubin (TcB) meters are widely used for screening newborns for jaundice, with a total serum bilirubin (TSB) measurement indicated when the TcB value is classified as "positive" by using a decision rule. The goal of our study was to assess the clinical utility of 3 recommended TcB screening decision rules. METHODS: Paired TcB/TSB measurements were collected at 34 newborn nursery sites. At 27 sites (sample 1), newborns were routinely screened with a TcB measurement. For sample 2, sites that typically screen with TSB levels also obtained a TcB measurement for the study. Three decision rules to define a positive TcB measurement were evaluated: ≥75th percentile on the Bhutani nomogram, 70% of the phototherapy level, and within 3 mg/dL of the phototherapy threshold. The primary outcome was a TSB level at/above the phototherapy threshold. The rate of false-negative TcB screens and percentage of blood draws avoided were calculated for each decision rule. RESULTS: For sample 1, data were analyzed on 911 paired TcB-TSB measurements from a total of 8316 TcB measurements. False-negative rates were <10% with all decision rules; none identified all 31 newborns with a TSB level at/above the phototherapy threshold. The percentage of blood draws avoided ranged from 79.4% to 90.7%. In sample 2, each rule correctly identified all 8 newborns with TSB levels at/above the phototherapy threshold. CONCLUSIONS: Although all of the decision rules can be used effectively to screen newborns for jaundice, each will "miss" some infants with a TSB level at/above the phototherapy threshold.

Clinical utility of transcutaneous bilirubinometer (TcB) in very low birth weight (VLBW) infants.

OBJECTIVE: This is a comprehensive study designed to evaluate the clinical usefulness of transcutaneous bilirubinometry (TcB) in very low birth weight (VLBW) newborns of African American (AA) descent. METHODS: TcB was conducted at the anterior superior iliac spine (ASIS), temporal region and sternum within 2 h of total serum bilirubin (TSB) measurements in newborns born at ≤32 weeks' gestation prospectively. Average (AVG) TcB levels were also calculated. The relationships between TSB and TcB levels were analyzed using non-parametric Spearman bivariate correlations, a Bland-Altman plot procedure and a decision tree (DT) analysis. RESULTS: One hundred newborns and 555 TSB data points were available. Eighty-nine percent of the newborns were AA. A significant correlation (P<0.0001) was observed between TSB and TcB values obtained at the ASIS (r=0.73), sternum (0.73), temporal region (0.61) and AVG (0.77). The Bland-Altman plot revealed a good agreement between AVG TcB values and TSB values. A DT analysis indicated that AVG TcB was also found to be the most significant predictor of TSB values in both the no phototherapy (PT) and biliblanket subgroups. CONCLUSION: TcB can be used reliably in VLBW AA newborns in the absence of overhead PT. The use of TcB in monitoring jaundice in VLBW newborns would help decrease the number of blood draws and cost of care.

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies.

UNLABELLED: Small-animal nuclear imaging modalities have become essential tools in the development process of new drugs, diagnostic procedures, and therapies. Quantification of metabolic or physiologic parameters is based on pharmacokinetic modeling of radiotracer biodistribution, which requires the blood input function in addition to tissue images. Such measurements are challenging in small animals because of their small blood volume. In this work, we propose a microfluidic counting system to monitor rodent blood radioactivity in real time, with high efficiency and small detection volume (∼1 µL). METHODS: A microfluidic channel is built directly above unpackaged p-i-n photodiodes to detect ß-particles with maximum efficiency. The device is embedded in a compact system comprising dedicated electronics, shielding, and pumping unit controlled by custom firmware to enable measurements next to small-animal scanners. Data corrections required to use the input function in pharmacokinetic models were established using calibrated solutions of the most common PET and SPECT radiotracers. Sensitivity, dead time, propagation delay, dispersion, background sensitivity, and the effect of sample temperature were characterized. The system was tested for pharmacokinetic studies in mice by quantifying myocardial perfusion and oxygen consumption with (11)C-acetate (PET) and by measuring the arterial input function using (99m)TcO4 (-) (SPECT). RESULTS: Sensitivity for PET isotopes reached 20%-47%, a 2- to 10-fold improvement relative to conventional catheter-based geometries. Furthermore, the system detected (99m)Tc-based SPECT tracers with an efficiency of 4%, an outcome not possible through a catheter. Correction for dead time was found to be unnecessary for small-animal experiments, whereas propagation delay and dispersion within the microfluidic channel were accurately corrected. Background activity and sample temperature were shown to have no influence on measurements. Finally, the system was successfully used in animal studies. CONCLUSION: A fully operational microfluidic blood-counting system for preclinical pharmacokinetic studies was developed. Microfluidics enabled reliable and high-efficiency measurement of the blood concentration of most common PET and SPECT radiotracers with high temporal resolution in small blood volume.

Transcutaneous bilirubinometry is a reliably conservative method of assessing neonatal jaundice.

OBJECTIVE: In order to reduce invasive testing in newborns prior to discharge, we tested the direction of the correlation between transcutaneous bilirubin (TcB) and total serum bilirubin (TSB), the likelihood of missing high TSBs with a raised threshold for confirmatory testing, and also calculated potential cost savings from fewer laboratory testing. METHODS: We performed a cross-sectional analysis of single paired TcB and TSB results measured at 36 ± 2 h of life in neonates ≥37 weeks admitted only to the Level 1 nursery. TcB was measured using the BiliChek® meter. RESULTS: Of the 552 infants, 512 (92.8%) had TSB levels below TcB values. Correlation between TcB and TSB was 0.69. If TSB confirmation was to be performed at 11.7 mg/dL (medium risk threshold for phototherapy), the negative predictive value was 99.4%, with a potential cost savings of $6555.00 ($1500.00 per 100 patients). Of the 495 infants with TcB <11.7 mg/dL, only 3 had TSB levels higher than 11.7 mg/dL, and none met phototherapy threshold for low risk infants. CONCLUSIONS: TcB screening at our institution has a high negative predictive value, and can be used as a stand-alone test until values are close to phototherapy threshold, thus reducing invasive testing and cost.

Determination of selenium in serum in the presence of gadolinium with ICP-QQQ-MS.

Gadolinium (Gd)-based magnetic resonance imaging (MRI) contrasting agents interfere with the determination of selenium (Se) when analysed by single quadrupole inductively coupled plasma-mass spectrometry (ICP-MS). This paper demonstrates that an ICP-triple quadrupole-MS (ICP-QQQ-MS) with oxygen mass shift overcomes Gd(++) interference on Se(+) and mitigates typically encountered matrix and spectral based interferences. Normal human serum was diluted in a solution containing isopropanol, EDTA, NH4OH and Triton X-100. Samples were unspiked (control) serum; serum spiked with 0.127 µmol L(-1) Se or 127 µmol L(-1) Gd; and serum spiked with both 0.127 µmol L(-1) Se and 127 µmol L(-1) Gd. Consideration of collision/reaction gases and conditions for interference mitigation included helium (He); a 'low' and 'high' hydrogen (H2) flow, and oxygen (O2). The instrument tune for O2 was optimised for effective elimination of interferences via a mass shift reaction of Se(+) to SeO(+). The ICP-QQQ-MS was capable of detecting trace (>9.34 nmol L(-1)) levels of Se in serum in the presence of Gd in our simulated post-MRI serum sample. The multi-tune capabilities of the ICP-QQQ-MS may be adapted to eliminate other specific isobaric interferences that cause false positive results in other analyses where the analyte is confounded by doubly charged and/or polyatomic species.

Generic automated method for liquid chromatography-multiple reaction monitoring mass spectrometry based monoclonal antibody quantitation for preclinical pharmacokinetic studies.

Quantitation of therapeutic monoclonal antibodies (mAb) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for pharmacokinetic (PK) studies is becoming an essential complement to traditional antibody-based ligand binding assays (LBA). Here we show an automated method to perform LC-MS/MS-based quantitation, with IgG1 conserved peptides, a heavy isotope labeled mAb internal standard, and anti-human Fc enrichment. All reagents in the method are commercially available with no requirement to develop novel assay-specific reagents. The method met traditional quantitative LC-MS/MS assay analytical characteristics in terms of precision, accuracy, and specificity. The method was applied to the pharmacokinetic study of a mAb dosed in cynomolgus monkey, and the results were compared with the immunoassay data. This methodology has the potential to benefit and accelerate the early biopharmaceutical development process, particularly by enabling PK analysis across species and candidate molecules with minimal method development.

Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D by LC-MS/MS involving derivatization with DMEQ-TAD.

CONTEXT: The discovery of hypercalcemic diseases due to loss-of-function mutations in 25-hydroxyvitamin D-24-hydroxylase has placed a new demand for sensitive and precise assays for 24,25-dihydroxyvitamin D [24,25-(OH)2D]. OBJECTIVE: We describe a novel liquid chromatography and tandem mass spectrometry-based method involving derivatization with DMEQ-TAD {4-[2-(6,7-dimethoxy-4-methyl-3,4-dihydroquinoxalinyl)ethyl]-1,2,4-triazoline-3,5-dione} to simultaneously assay multiple vitamin D metabolites including 25-hydroxyvitamin D (25-OH-D) and 24,25-(OH)2D using 100 µL of serum with a 5-minute run time. DESIGN: The assay uses a newly synthesized internal standard d6-24,25-(OH)2D3 enabling the quantitation of 24,25-(OH)2D3 as well as the determination of the ratio of 25-OH-D3 to 24,25-(OH)2D3, a physiologically useful parameter. SETTING: We report data on more than 1000 normal and disease samples involving vitamin D deficiency or hypercalcemia in addition to studies involving knockout mouse models. RESULTS: The assay showed good correlation with samples from quality assurance schemes for 25-OH-D (25-OH-D2 and 25-OH-D3) determination (-2% to -5% bias) and exhibited low inter- and intraassay coefficients of variation (4%-7%) and lower limits of quantitation of 0.25-0.45 nmol/L. In clinical studies, we found a strong correlation between serum levels of 25-OH-D3 and 24,25-(OH)2D3 (r(2) = 0.80) in subjects over a broad range of 25-OH-D3 values and a marked lack of production of 24,25-(OH)2D3 below 25 nmol/L of 25-OH-D. The ratio of 25-OH-D3 to 24,25-(OH)2D3, which remained less than 25 in vitamin D-sufficient subjects (serum 25-OH-D < 50 nmol/L) but was greatly elevated (80-100) in patients with idiopathic infantile hypercalcemia. CONCLUSIONS: The new method showed good utility in clinical settings involving vitamin D deficiency; supplementation with vitamin D and idiopathic infantile hypercalcemia, as well as in animal models with ablation of selected cytochrome P450-containing enzymes involved in vitamin D metabolism.

Point-of-Care device for quantification of zinc in serum.

With 42,000 cases reported annually in the United States and an approximate 10% mortality rate, [1] pediatric septic shock is a major health problem that is often difficult to treat effectively. Several studies have shown that children experiencing pediatric septic shock often have critically low levels of serum zinc (Zn), suggesting supplementation of Zn to be an effective therapeutic strategy. However, to protect the safety and well-being of the patient, it is extremely important to monitor blood serum concentration of Zn during supplementation in order to ensure that levels remain at or near the physiological norm and thus minimize the risk of heavy metal toxicity from over supplementation. Current methods for quantifying Zn in serum typically require sending serum samples to external laboratory facilities resulting in turnaround times ranging from hours to a few days. Therefore, timely monitoring of Zn levels in serum is often not possible in the clinical setting which ultimately limits the ability to use Zn supplementation as a therapeutic intervention. This paper reports on the development of a Point-of-Care device for rapid electrochemical measurement of Zn in serum. The device is centered on a three electrode sensor which uses Anodic stripping voltammetry (ASV) for sensing Zn levels. The Cu based sensor is read using a reader that has been developed using commercially available embedded system parts in combination with custom analog circuitry that is able to produce quantification results in approximately 6 minutes.

Development of a highly sensitive and selective hyphenated technique (molecularly imprinted micro-solid phase extraction fiber-molecularly imprinted polymer fiber sensor) for ultratrace analysis of folic acid.

A simple polymerization strategy is reported in this work which allows molecularly imprinted polymeric fiber (monolith) fabrication for direct use in sensing devices. This is advantageous for achieving higher degree of enrichment of target analyte (folic acid) from the complex matrices of real samples, without any surface fouling, cross-reactivity, and non-specific (false-positive) contributions. In order to measure serum folic acid at ultratrace level to detect spina bifida, a neural tube defect in mother, and other acute cases of proteomic diseases, the hyphenation between molecularly imprinted micro-solid phase extraction fiber and a complementary molecularly imprinted polymer-carbon composite fiber sensor has been found quite efficient. The primitive diagnosis of many chronic diseases is feasible by estimating folic acid as biomarker, with the detection limit as low as 0.0036 ng mL(-1) (relative standard deviation=0.13%, signal/noise=3) in human blood serum.

Evaluation of analytical methods and workflow performance of the Architect ci8200 integrated serum/plasma analyzer system.

BACKGROUND: The Architect ci8200 is an integrated serum analyzer for photometric, electrochemical and immunological assays. Several assays of each category and the workflow performance of the system were compared with established laboratory procedures in two laboratories. METHODS: Measurements were compared with the ELECSYS 2010 (Roche Diagnostics) for CEA, PSA, FPSA, AFP, folate, vitamin B12, with the CENTAUR (Bayer) for TSH, T4, FT4, FSH and Estradiol, with the LIAISON (DiaSorin) for TSH, FT4 and FT3, with the Behring Nephelometer BN II (Dade-Behring) for ferritin, and with the INTEGRA 800 (Roche Diagnostics), and the AU640 (Olympus) for clinical chemistry assays. Workflow studies were performed to compare times of analysis required for defined analytical workloads. RESULTS: The coefficients of variation (CVs) for within-run imprecision were between 3% and 6% for CEA, PSA, FPSA, AFP and ferritin, and between 3% and 11% for TSH, FT4, FT3, folate and vitamin B12. The CVs for day-to-day imprecision for immunoassays were between 3% and 10%, except for vitamin B12 (CVs 11-13%) and FT4 (CV 10% -13%). For clinical chemistry tests corresponding CVs for within-run imprecision were < 1%, except for HDL, triglyceride, creatinine, ALT, LD and lipase (CVs<2%) and bicarbonate (CV 3%-6%) and magnesium (CV < 3%). The CVs for day-to-day imprecision for clinical chemistry tests were < 1%, except for sodium, CO(2), magnesium, phosphorus, glucose, uric acid, HDL, triglyceride, ALT, AST CK, lipase with CVs < 6% and for CO(2)<11%. Dilutional linearity testing of seven immunoassays and five clinical chemistry analytes resulted in recovery rates of 90-110%. Correlation studies with 15 immunoassays and 25 clinical chemistry tests showed acceptable agreements with established methods. Work flow analyses demonstrated a net gain in time of analysis up to 109 min depending on the size of the sample batch analyzed with the Architect ci8200 as the main analyzer as compared to the currently installed routine laboratory equipment. Median turn-around times were 7 and 30 min for chemistry assays and immunoassays, respectively, when ordered as STAT analyses, and 18 min when chemistry assays were ordered as routine determinations. CONCLUSIONS: Assays on the Architect ci8200 performed well, fulfilling quality control requirements as defined for instance by German quality control guidelines (RiliBAK). Method comparisons showed acceptable agreements with established assays. Workflow studies using the Architect ci8200 documented shorter times of analyses as compared with the conventionally established laboratory routine demonstrating the potential of integrated chemistry/immunoassay analyzers to provide faster and more efficient performance.

Detection of serum uric acid using the optical polymeric enzyme biochip system.

An optical polymeric biochip system based on the complementary metal oxide semiconductor (CMOS) photo array sensor and polymeric enzyme biochip for rapidly quantitating uric acid in a one-step procedure was developed. The CMOS sensor was designed with N(+)/P-well structure and manufactured using a standard 0.5 microm CMOS process. The polymeric enzyme biochip was immobilized with uricase-peroxidase and used to fill the reacting medium with the sample. This study encompasses the cloning of the Bacillus subtilis uricase gene and expression in Escherichia coli, as well as the purification of uricase and measurement of its activity. The cloned uricase gene included an open reading frame of 1491 nucleotides that encodes a protein of approximately 55 kDa. The expression of the putative MBP-fusion protein involved approximately 98 kDa of the protein. The CMOS sensor response was stronger at a higher temperature range of 20-40 degrees C, with optimal pH at 8.5. The calibration curve of purified uric acid was linear in the concentration range from 2.5 to 12.5 mg/dL. The results obtained for serum uric acid correlated quite closely with those obtained using the Beckman Synchron method.

Evaluation of the i-STAT Portable Clinical Analyzer for point-of-care blood testing in the intensive care units of a university children's hospital.

We evaluated the analytical performance of the i-STAT Portable Clinical Analyzer (PCA), a point-of-care testing system consisting of a hand-held analyzer and single-use cartridges that measure different panels of electrolytes, metabolites, blood gases, and hematocrit in 65-100 microl of blood. Our objective was to determine whether PCA measurements at the bedside of patients in the neonatal and pediatric intensive care units of the MUSC Children's Hospital would be as reliable as those performed by the clinical laboratory's primary methods (Radiometer ABL 725 blood gas analyzer; Vitros 750 chemistry analyzer; and Coulter STKS hematology analyzer). Four cartridge types: (a) EC8+ (sodium; potassium; chloride; urea; glucose; pH; blood gases [PO2; pCO2]), (b) EC6+ (sodium; potassium; ionized calcium; glucose; hematocrit; pH), (c) G3+ (pH; PO2; pCO2), and (d) creatinine, were assessed for reproducibility, linearity, and method comparisons using aqueous samples, blood samples supplemented with several analytes, and -225 blood samples from patients. Reproducibility (CV) was good (< 2%) for electrolytes, glucose, urea, and pH, satisfactory (< 6.5%) for blood gases and creatinine, but poor (21%) for hematocrit. Linearity concentrations spanning the clinically relevant ranges were verified for all analytes. Method comparison studies with samples separated into 2 subgroups by patient age (> or < 3 mo) showed that agreement between the PCA and the primary methods was clinically acceptable. After the PCA was implemented for clinical testing, the observation of discrepant results of creatinine concentrations in neonatal blood samples that would have affected clinical management led to a second creatinine comparison study (59 additional samples) and to our eventual discontinuation of the PCA creatinine assay. This problem notwithstanding, the successful implementation of the PCA is attributed to careful analytical evaluations and ongoing communication with the clinical staff.

Inaccuracy of lipid measurements with the portable Cholestech L.D.X analyzer in patients with hypercholesterolemia.

BACKGROUND: Although total cholesterol concentrations measured by portable lipid analyzers have acceptable bias and precision in young and middle-aged adults, clinically relevant differences in HDL-cholesterol (HDL-C) and triglyceride values have been described. Furthermore, the accuracy of portable lipid analyzers in older hyperlipidemic individuals, who have a high incidence of coronary heart disease, has not been validated. This study determined the biases and variability in portable lipid measurements in older patients with hypercholesterolemia and related them to National Cholesterol Education Program Adult Treatment Panel III guidelines. METHODS: Participants were > or =70 years of age with fasting serum LDL-cholesterol (LDL-C) concentrations > 1.40 g/L. Fasting fingerstick samples were analyzed on a Cholestech L.D.X desktop analyzer. Antecubital venous samples were analyzed in a proficiency-certified clinical laboratory. RESULTS: Portable measurements systematically overestimated triglycerides (0.296 g/L; P <0.001) and HDL-C (0.015 g/L; P = 0.026). LDL-C concentrations were underestimated (0.043 g/L; P = 0.046). Total and non-HDL cholesterol calculations based on the portable lipid device provided unbiased estimates, but wide variability was present. Significant variability in lipid determinations limited their clinical usefulness in individual patients, especially because 2 SD of the mean bias between the laboratory and the portable determinations of LDL-C and non-HDL cholesterol exceeded the 0.30 g/L cutoff that defines treatment targets in the current lipid guidelines. CONCLUSIONS: Lipid values obtained from portable lipid analyzers may be useful for screening, but they should not be used to make clinical decisions regarding the diagnosis and management of dyslipidemia in individual patients.