Towards a “Sample-In, Answer-Out” Point-of-Care Platform for Nucleic Acid Extraction and Amplification: Using an HPV E6/E7 mRNA Model System

The paper presents the development of a “proof-of-principle” hands-free and self-contained diagnostic platform for detection of human papillomavirus (HPV) E6/E7 mRNA in clinical specimens. The automated platform performs chip-based sample preconcentration, nucleic acid extraction, amplification, and real-time fluorescent detection with minimal user interfacing. It consists of two modular prototypes, one for sample preparation and one for amplification and detection; however, a common interface is available to facilitate later integration into one single module. Nucleic acid extracts (n = 28) from cervical cytology specimens extracted on the sample preparation chip were tested using the PreTect HPV-Proofer and achieved an overall detection rate for HPV across all dilutions of 50%–85.7%. A subset of 6 clinical samples extracted on the sample preparation chip module was chosen for complete validation on the NASBA chip module. For 4 of the samples, a 100% amplification for HPV 16 or 33 was obtained at the 1 : 10 dilution for microfluidic channels that filled correctly. The modules of a “sample-in, answer-out” diagnostic platform have been demonstrated from clinical sample input through sample preparation, amplification and final detection

Frequency-Resolved High-Frequency Broadband Measurement of Acoustic Longitudinal Waves by Laser-Based Excitation and Detection

Optoacoustics is a metrology widely used for material characterisation. In this study, a measurement setup for the selective determination of the frequency-resolved phase velocities and attenuations of longitudinal waves over a wide frequency range (3–55 MHz) is presented. The ultrasonic waves in this setup were excited by a pulsed laser within an absorption layer in the thermoelastic regime and directed through a layer of water onto a sample. The acoustic waves were detected using a self-built adaptive interferometer with a photorefractive crystal. The instrument transmits compression waves only, is low-contact, non-destructive, and has a sample-independent excitation. The limitations of the approach were studied both by simulation and experiments to determine how the frequency range and precision can be improved. It was shown that measurements are possible for all investigated materials (silicon, silicone, aluminium, and water) and that the relative error for the phase velocity is less than 0.2%

On Dispersion Compensation for GAW-Based Structural Health Monitoring

Guided acoustic waves (GAW) have proven to be a useful tool for structural health monitoring (SHM). However, the dispersive nature of commonly used Lamb waves compromises the spatial resolution making it difficult to detect small or weakly reflective defects. Here we demonstrate an approach that can compensate for the dispersive effects, allowing advanced algorithms to be used with significantly higher signal-to-noise ratio and spatial resolution. In this paper, the sign coherence factor (SCF) extension of the total focusing method (TFM) algorithm is used. The effectiveness is examined by numerical simulation and experimentally demonstrated by detecting weakly reflective layers with a highly dispersive A0 mode on an aluminum plate, which are not detectable without compensating for the dispersion effects

Simulating copolymeric nanoparticle assembly in the co-solvent method: How mixing rates control final particle sizes and morphologies

The self-assembly of copolymeric vesicles and micelles in micromixers is studied by External Potential Dynamics (EPD) simulations – a dynamic density functional approach that explicitly accounts for the polymer architecture both at the level of thermodynamics and dynamics. Specifically, we focus on the co-solvent method, where nanoparticle precipitation is triggered by mixing a poor co-solvent into a homogeneous copolymer solution in a micromixer. Experimentally, it has been reported that the flow rate in the micromixers influences the size of the resulting particles as well as their morphology: At small flow rates, vesicles dominate; with increasing flow rate, more and more micelles form, and the size of the particles decreases. Our simulation model is based on the assumption that the flow rate mainly sets the rate of mixing of solvent and co-solvent. The simulations reproduce the experimental observations at an almost quantitative level and provide insight into the underlying physical mechanisms: First, they confirm an earlier conjecture according to which the size control takes place in the earliest stage of the particle self-assembly, during the spinodal decomposition of polymers and solvent. Second, they reveal a crossover between different morphological regimes as a function of mixing rate. Hence they demonstrate that varying the mixing rate in a co-solvent setup is an effective way to control two key properties of drug delivery systems, their mean size and their morphology

Systematic classification of micromixers

This work is a systematic classification of passive micromixers according to their performance. The basis is the introduction of an efficiency measure which relates both mixing quality and pressure drop. This measure is then applied to data from several experimental characterizations. It is found that micromixers can be classified into two groups: inertial micromixers with a strong increase in performance above a critical flow rate and mixers based on lamination with a continuous change of the efficiency with growing Reynolds number. This classification is achieved by analysis of the mixing performance rather than describing the mixing principle

Dynamic model for investigation of instabilities in microchannel evaporators

Microchannel evaporators are widely used for both cooling applications and for vapor generation in process engineering. They allow high heat transfer rates within minimal space. However, the massive changes of the fluids properties during evaporation can trigger different types of instabilities. These mostly undesired effects are caused by complex interactions of heat conduction, heat transfer and fluid flow within the evaporator. A comprehensive dynamic model is developed to obtain a deeper understanding of the effects occurring her. Experimental validations show that the model is capable of correctly predicting the pressure drop behavior of practical microchannel evaporators