Abstract. In response to increasing calls for the reform of the undergraduate science curriculum for life science majors and pre-medical students (Bio2010, Scientific Foundations for Future Physicians, Vision & Change), an interdisciplinary team has created NEXUS/Physics: a repurposing of an introductory physics curriculum for the life sciences. The curriculum interacts strongly and supportively with introductory biology and chemistry courses taken by life sciences students, with the goal of helping students build general, multi-discipline scientific competencies. In order to do this, our two-semester NEXUS/Physics course sequence is positioned as a second year course so students will have had some exposure to basic concepts in biology and chemistry. NEXUS/Physics stresses interdisciplinary examples and the content differs markedly from traditional introductory physics to facilitate this. It extends the discussion of energy to include interatomic potentials and chemical reactions, the discussion of thermodynamics to include enthalpy and Gibbs free energy, and includes a serious discussion of random vs. coherent motion including diffusion. The development of instructional materials is coordinated with careful education research. Both the new content and the results of the research are described in a series of papers for which this paper serves as an overview and context.
The axial resolution of three-dimensional structured illumination microscopy (3D SIM) is limited to ∼300 nm. Here we present two distinct, complementary methods to improve axial resolution in 3D SIM with minimal or no modification to the optical system. We show that placing a mirror directly opposite the sample enables four-beam interference with higher spatial frequency content than 3D SIM illumination, offering near-isotropic imaging with ∼120-nm lateral and 160-nm axial resolution. We also developed a deep learning method achieving ∼120-nm isotropic resolution. This method can be combined with denoising to facilitate volumetric imaging spanning dozens of timepoints. We demonstrate the potential of these advances by imaging a variety of cellular samples, delineating the nanoscale distribution of vimentin and microtubule filaments, observing the relative positions of caveolar coat proteins and lysosomal markers and visualizing cytoskeletal dynamics within T cells in the early stages of immune synapse formation.
We combined instant structured illumination microscopy (iSIM) with total internal reflection fluorescence microscopy (TIRFM) in an approach referred to as instant TIRF-SIM, thereby improving the lateral spatial resolution of TIRFM to 115 ± 13 nm without compromising speed, and enabling imaging frame rates up to 100 Hz over hundreds of time points. We applied instant TIRF-SIM to multiple live samples and achieved rapid, high-contrast super-resolution imaging close to the coverslip surface.
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