Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies

Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery.United States. Army Research Office (Grant W911NF-12-2-0039

The Refined Consensus Model of Pedagogical Content Knowledge in Science Education

This chapter chronicles the developmental journey of a model for teacher pedagogical content knowledge (PCK) in science education, now identified as the Refined Consensus Model (RCM) of PCK, that represents the contributions and collective thinking of two dozen international researchers in science teacher education. This journey starts by recounting the process that led to an update and significant revisions to the model of teacher professional knowledge and skills including PCK (informally known as the 2012 Consensus Model (CM)). Then, we unpack and describe the different components of the model in both diagrammatic form and in explanatory text. The RCM describes the complex layers of knowledge and experiences that shape and inform teachers’ practice and mediate student outcomes. A key feature of this model is the identification of three distinct realms of PCK—collective PCK, personal PCK, and enacted PCK. These realms are used to situate the specialised professional knowledge held by different science educators in different settings ranging from the collected knowledge understood by many to the unique subset of knowledge an individual teacher draws upon. The model also recognises that the broader professional knowledge bases are foundational to teacher PCK while the learning context a teacher is working in can greatly influence the teaching and learning that takes place