Self-Aligned Acoustofluidic Particle Focusing and Patterning in Microfluidic Channels from Channel-Based Acoustic Waveguides

Acoustic fields have been widely used for manipulation of particles and cells within microfluidic systems. In this Letter, we explore a novel acoustofluidic phenomenon for particle patterning and focusing, where a periodic acoustic pressure field is produced parallel to internal channel boundaries with the imposition of either a traveling or standing surface acoustic wave (SAW). This effect results from the propagation and intersection of edge waves from the channel walls according to the Huygens-Fresnel principle and classical wave fronts from the substrate-fluid interface. We demonstrate versatile control over this effect to produce both one- and two-dimensional acoustic patterning from one-dimensional SAW fields and its utility for continuous particle focusing. Uniquely, this channel-guided acoustic focusing permits the generation of robust acoustic fields without channel resonance conditions and particle focusing positions that are difficult or impossible to produce otherwise

Automated tumour recognition and digital pathology scoring unravels new role for PD-L1 in predicting good outcome in ER-/HER2+ breast cancer

The role of PD-L1 as a prognostic and predictive biomarker is an area of great interest. However, there is a lack of consensus on how to deliver PD-L1 as a clinical biomarker. At the heart of this conundrum is the subjective scoring of PD-L1 IHC in most studies to date. Current standard scoring systems involve separation of epithelial and inflammatory cells and find clinical significance in different percentages of expression, e.g., above or below 1%. Clearly, an objective, reproducible and accurate approach to PD-L1 scoring would bring a degree of necessary consistency to this landscape. Using a systematic comparison of technologies and the application of QuPath, a digital pathology platform, we show that high PD-L1 expression is associated with improved clinical outcome in Triple Negative breast cancer in the context of standard of care (SoC) chemotherapy, consistent with previous findings. In addition, we demonstrate for the first time that high PD-L1 expression is also associated with better outcome in ER- disease as a whole including HER2+ breast cancer. We demonstrate the influence of antibody choice on quantification and clinical impact with the Ventana antibody (SP142) providing the most robust assay in our hands. Through sampling different regions of the tumour, we show that tumour rich regions display the greatest range of PD-L1 expression and this has the most clinical significance compared to stroma and lymphoid rich areas. Furthermore, we observe that both inflammatory and epithelial PD-L1 expression are associated with improved survival in the context of chemotherapy. Moreover, as seen with PD-L1 inhibitor studies, a low threshold of PD-L1 expression stratifies patient outcome. This emphasises the importance of using digital pathology and precise biomarker quantitation to achieve accurate and reproducible scores that can discriminate low PD-L1 expression