Centrifugal microfluidics has evolved into a mature technology. Several major diagnostic companies either have products on the market or are currently evaluating centrifugal microfluidics for product ...development. The fields of application are widespread and include clinical chemistry, immunodiagnostics and protein analysis, cell handling, molecular diagnostics, as well as food, water, and soil analysis. Nevertheless, new fluidic functions and applications that expand the possibilities of centrifugal microfluidics are being introduced at a high pace. In this review, we first present an up-to-date comprehensive overview of centrifugal microfluidic unit operations. Then, we introduce the term "process chain" to review how these unit operations can be combined for the automation of laboratory workflows. Such aggregation of basic functionalities enables efficient fluidic design at a higher level of integration. Furthermore, we analyze how novel, ground-breaking unit operations may foster the integration of more complex applications. Among these are the storage of pneumatic energy to realize complex switching sequences or to pump liquids radially inward, as well as the complete pre-storage and release of reagents. In this context, centrifugal microfluidics provides major advantages over other microfluidic actuation principles: the pulse-free inertial liquid propulsion provided by centrifugal microfluidics allows for closed fluidic systems that are free of any interfaces to external pumps. Processed volumes are easily scalable from nanoliters to milliliters. Volume forces can be adjusted by rotation and thus, even for very small volumes, surface forces may easily be overcome in the centrifugal gravity field which enables the efficient separation of nanoliter volumes from channels, chambers or sensor matrixes as well as the removal of any disturbing bubbles. In summary, centrifugal microfluidics takes advantage of a comprehensive set of fluidic unit operations such as liquid transport, metering, mixing and valving. The available unit operations cover the entire range of automated liquid handling requirements and enable efficient miniaturization, parallelization, and integration of assays.
Review on miniaturization, integration, and automation of laboratory processes within centrifugal microfluidic platforms. For efficient implementation of applications, building blocks are categorized into unit operations and process chains.
Liquid chromatography coupled to mass spectrometry (LC–MS/MS) is increasingly used as a routine methodology in clinical laboratories for the analysis of low molecular weight molecules. The high ...specificity in combination with high sensitivity and multi-analyte potential makes it an attractive complementary method to traditional methodology used for routine applications. Its strength and weaknesses in this context will be discussed and examples of successful clinical applications will be given. For LC–MS/MS to truly fulfil its promise in clinical diagnosis, the prerequisite steps being sample pre-treatment, chromatographic separation and detection by selected reaction monitoring must become more integrated as they are in conventional clinical analysers. The availability of ready-to-use reagents kits, eliminating efforts needed for method development and extensive validation, are likely to contribute to a wider acceptance of LC–MS/MS in clinical laboratories. Growing applicability of LC–MS/MS in the clinical laboratory field is expected from quantitative protein analysis.
For many years the concept of patient-based quality control (QC) has been discussed and implemented in hematology laboratories; however, the techniques have not been widely implemented in clinical ...chemistry. This is mainly because of the complexity of this form of QC, as it needs to be optimized for each population and often for each analyte. However, the clear advantages of this form of QC, together with the ongoing realization of the shortcomings of "conventional" QC, have driven a need to provide guidance to laboratories to assist in deploying patient-based QC. This overview describes the components of a patient-based QC system (calculation algorithm, block size, truncation limits, control limits) and the relationship of these to the analyte being controlled. We also discuss the need for patient-based QC system optimization using patient data from the individual testing laboratory to reliably detect systematic errors while ensuring that there are few false alarms. The term patient-based real-time quality control covers many activities that use data from patient samples to detect analytical errors. These activities include the monitoring of patient population parameters such as the mean or median analyte value or using single within-patient changes such as the delta check. In this report, we will restrict the discussion to population-based parameters. This overview is intended to serve as a guide for the implementation of a patient-based QC system. The report does not cover the clinical evaluation of the population.
To establish gestational phase adapted cutoffs for the use of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio as a diagnostic tool for preeclampsia in the ...clinical setting, a multicenter case–control study including a total of 1149 patients was performed. We report normal values of sFlt-1, PlGF, and the sFlt-1/PlGF ratio based on the analysis of a total of 877 patients with uneventful pregnancy outcome. A total of 234 patients with preeclampsia and a matched cohort consisting of 468 patients with normal pregnancy outcome were compared, and sFlt-1 and PlGF were measured on an automated platform. Separate cutoffs for the sFlt-1/PlGF ratio were determined for the early (20+0–33+6 weeks) and the late gestational phase (34+0 weeks–delivery). For each of the 2 gestational phases, 2 independent cutoffs framing an equivocal zone were determinedthe first cutoff with focus on high sensitivity, and the second focusing on high specificity. Between 20+0 and 33+6 weeks, the cutoffs at ≤33 and ≥85 resulted in a sensitivity/specificity of 95%/94% and 88%/99.5%, respectively. An sFlt-1/PlGF ratio of ≤33 had the lowest likelihood of a negative test (0.05; 95% confidence interval, 0.02–0.13), whereas values ≥85 had the highest likelihood of a positive test (176; 95% confidence interval, 24.88–1245). After 34+0 weeks, the cutoffs at ≤33 and ≥110 yielded a sensitivity/specificity of 89.6%/73.1% and 58.2%/95.5%, respectively. The approach to use multiple cutoffs for the early and late gestational phase enhances the diagnostic accuracy of the sFlt-1/PlGF ratio as a diagnostic tool for preeclampsia.
The objective of the study was to evaluate the current state of clinical assays for total and free testosterone.
The five participants were appointed by the Council of The Endocrine Society and ...charged with attaining the objective using published data and expert opinion.
Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants.
The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations.
Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and free testosterone should be established for both genders and children, taking into account the many variables that influence serum testosterone concentration.
MALDI-TOF mass spectrometry (MS) is set to make inroads into clinical chemistry because it offers advantages over other analytical platforms. These advantages include low acquisition and operating ...costs, ease of use, ruggedness, and high throughput. When coupled with innovative front-end strategies and applied to important clinical problems, it can deliver rapid, sensitive, and cost-effective assays.
This review describes the general principles of MALDI-TOF MS, highlights the unique features of the platform, and discusses some practical methods based upon it. There is substantial potential for MALDI-TOF MS to make further inroads into clinical chemistry because of the selectivity of mass detection and its ability to independently quantify proteoforms.
MALDI-TOF MS has already transformed the practice of clinical microbiology and this review illustrates how and why it is now set to play an increasingly important role in in vitro diagnostics in particular, and clinical chemistry in general.
We described an automated technique for measurement of serum nitrite/nitrate (NO
x
) using the Cobas Mira clinical chemistry analyzer.
NO
x
was measured by the modified Griess method. Precision, ...accuracy, linearity, instrument carry-over and lower limit of quantitation (LLOQ) were assessed.
The automated technique for measurement of serum NO
x
was linear, precise, and accurate. It has a LLOQ of 2.0
μmol/L.
Serum NO
x
measured by the modified Griess method can be applied easily to the Cobas Mira clinical chemistry analyzer.
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