A peak-clustering method for MEG group analysis to minimise artefacts due to smoothness

Magnetoencephalography (MEG), a non-invasive technique for characterizing brain electrical activity, is gaining popularity as a tool for assessing group-level differences between experimental conditions. One method for assessing task-condition effects involves beamforming, where a weighted sum of field measurements is used to tune activity on a voxel-by-voxel basis. However, this method has been shown to produce inhomogeneous smoothness differences as a function of signal-to-noise across a volumetric image, which can then produce false positives at the group level. Here we describe a novel method for group-level analysis with MEG beamformer images that utilizes the peak locations within each participant's volumetric image to assess group-level effects. We compared our peak-clustering algorithm with SnPM using simulated data. We found that our method was immune to artefactual group effects that can arise as a result of inhomogeneous smoothness differences across a volumetric image. We also used our peak-clustering algorithm on experimental data and found that regions were identified that corresponded with task-related regions identified in the literature. These findings suggest that our technique is a robust method for group-level analysis with MEG beamformer images.

High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics.