Systematic review of centrifugal valving based on digital twin modeling towards highly integrated lab-on-a-disc systems

Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control which mainly depend on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates efficient simulation tools for virtual prototyping and characterization and algorithmic design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, layout, fluidic testing, bioanalytical validation, and scale-up to commercial mass manufacture.

Systematic Review of Centrifugal Valving Based on Digital Twin Modelling towards Highly Integrated Lab-on-a-Disc Systems

Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control mainly based on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates the provision of efficient simulation tools for virtual prototyping and characterization to greatly expedite design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, fluidic testing, bioanalytical validation and scale-up to commercial mass manufacture.

Systematic Review of Centrifugal Valving Based on Digital Twin Modelling towards Highly Integrated Lab-on-a-Disc Systems

Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control mainly based on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates the provision of efficient simulation tools for virtual prototyping and characterization to greatly expedite design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, fluidic testing, bioanalytical validation and scale-up to commercial mass manufacture.

Development and Validation of an UPLC-MS/MS method for the Simultaneous determination of Verapamil and Trandolapril in Rat Plasma: Application to a Pharmacokinetic Study

Background: Verapamil is an excellent drug for the medication of hypertension and Trandolapril is an angiotensin-converting-enzyme inhibitor. So, it is an interesting method to develop a novel and reliable MS/UPLC strategy for simultaneous establishment of Verapamil and Trandolapril. Objective: To develop a new rapid and sensitive UPLC-MS/MS method for the simultaneous estimation of Verapamil and Trandolapril in rat plasma using D6-Verapamil and D6-Trandolapril. Method: Separation was carried on column Symmetry C18 column (150x4.6mm, 3.5µm) using a isocratic elution with a buffer containing 1mL of Formic acid in 1Lit of water and the mixture of two components like Buffer and Acetonitrile in the ratio of 80:20 as mobile phase with 1mL/min flow rate at ambient temperature. Results: Analysis was performed within 5 minutes over a good linear concentration range from 2.4ng/mL to 48ng/mL(r2 = 0.9993 ± 0.018) for Verapamil and 10pg/mL to 200pg/mL(r2 =0.9993± 0.006) for Trandolapril .The extraction recoveries and matrix effect of verapamil and Trandolapril were 98.45,99.95, 98.12, 99.66% and 98.27,99.89, 97.78, 99.23% at different QC concentration levels. Precision and recovery study results are within the acceptable limit. An electro spray ionization source was used to study verapamil and Trandolapril at m/z 454.72→182.16, 430.25→201.48 and IS for m/z 460.18→ 324.39, 436.28 → 340.52 were ion pairs of mass analysis. This method has been successfully applied, exploring Verapamil (1.2mg/kg) with its internal standard (D6-Verapamil), Trandolapril (0.005mg/kg) with its internal standard (D6-Trandolapril) were extracted from rat plasma using liquid -liquid extraction. Conclusion: This manuscript focuses on the consistent evaluation of the key Bioanalytical validation parameters and the following are discussed: accuracy, precision, sensitivity, selectivity, standard curve, limits of quantification, range, recovery, and stability. These validation parameters are described, together with illustrations of validation methodology applied in the case of chromatographic methods used in bio analysis.

Determination of donepezil in spiked rabbit plasma by high-performance liquid chromatography with fluorescence detection

The aim of this paper is to develop sensitive, accurate, reproducible and robust RP-HPLC with fluorescence detection for estimation of donepezil (DZ) in rabbit plasma using silodosin as the internal standard (IS). The prepared samples were quantified on reversed phase column Luna C 18(2) (150 × 4.6 mm i.d., 5 µm particle size) operated at room temperature using the mobile phase consisting of methanol: 0.1% acetic acid (50 : 50, v/v) at a flow rate of 1 ml min −1 . The method was fully validated according to bioanalytical validation guidelines of FDA in terms of system suitability, selectivity, sensitivity, precision and stability. It was found that the increase in peak areas followed the increase of DZ concentration in the range of 2.56–200.00 ng ml −1 with LOD of 0.85 ng ml −1 . The method was successfully applied for the determination of DZ in rabbit plasma using manual shaking dispersive liquid–liquid microextraction.