Microscale robotic devices have myriad potential applications including drug delivery, biosensing, cell manipulation, and microsurgery. In this work, a tethered, 3D, compliant grasper with an integrated force sensor is presented, the entirety of which is fabricated on the tip of an optical fiber in a single‐step process using 2‐photon polymerization. This gripper can prove useful for the interrogation of biological microstructures such as alveoli, villi, or even individual cells. The position of the passively actuated grasper is controlled via micromanipulation of the optical fiber, and the microrobotic device measures approximately 100 µm in length and breadth. The force estimation is achieved using optical interferometry: high‐dimensional spectral readings are used to train artificial neural networks to predict the axial force exerted on/by the gripper. The design, characterization, and testing of the grasper are described and its real‐time force‐sensing capability with an accuracy below 2.7% of the maximum calibrated force is demonstrated.
The viscosity is a highly important parameter within the cell membrane, affecting the diffusion of small molecules and, hence, controlling the rates of intracellular reactions. There is significant interest in the direct, quantitative assessment of membrane viscosity. Here we report the use of fluorescence lifetime imaging microscopy of the molecular rotor BODIPY C10 in the membranes of live Escherichia coli bacteria to permit direct quantification of the viscosity. Using this approach, we investigated the viscosity in live E. coli cells, spheroplasts, and liposomes made from E. coli membrane extracts. For live cells and spheroplasts, the viscosity was measured at both room temperature (23°C) and the E. coli growth temperature (37°C), while the membrane extract liposomes were studied over a range of measurement temperatures (5-40°C). At 37°C, we recorded a membrane viscosity in live E. coli cells of 950 cP, which is considerably higher than that previously observed in other live cell membranes (e.g., eukaryotic cells, membranes of Bacillus vegetative cells). Interestingly, this indicates that E. coli cells exhibit a high degree of lipid ordering within their liquid-phase plasma membranes.
This study presents a novel fiber‐optic surface‐enhanced Raman spectroscopy (SERS) probe (SERS‐on‐a‐tip) fabricated using a simple, two‐step protocol based on off‐the‐shelf components and materials, with a high degree of controllability and repeatability. Two‐photon polymerization and subsequent metallization are adopted to fabricate a range of SERS arrays on both planar substrates and end‐facets of optical fibers. For the SERS‐on‐a‐tip probes, a limit of detection of 10−7 m (Rhodamine 6G) and analytical enhancement factors of up to 1300 are obtained by optimizing the design, geometry, and alignment of the SERS arrays on the tip of the optical fiber. Furthermore, strong repeatability and consistency are achieved for the fabricated SERS arrays, demonstrating that the technique may be suitable for large‐scale fabrication procedures in the future. Finally, rapid SERS detection of live Escherichia coli cells is demonstrated using integration times in the milliseconds to seconds range. This result indicates strong potential for in vivo diagnostic use, particularly for detection of infections. Moreover, to the best of our knowledge, this represents the first report of detection of live, unlabeled bacteria using a fiber‐optic SERS probe.
We present an approach to laser scanning endomicroscopy that requires no moving parts and can be implemented with no distal scanners or optics, permitting extremely compact endoscopic probes to be developed. Our approach utilizes a spatial light modulator to correct for phase variations across a fiber imaging bundle and to encode for arbitrary wavefronts at the distal end of the fiber bundle. Thus, it is possible to realize both focusing and beam scanning at the output of the fiber bundle with no distal components. We present proof of principle results to illustrate three-dimensional scanning of the focal spot and exemplar images of a United States Air Force resolution test chart.
A series of seven new metal complexes (metal = NiII, CuII, PtII and VO2+) with substituted salphen ligands have been prepared and their duplex and G-quadruplex DNA affinities determined. The selectivity of the complexes towards a given DNA topology is dictated by several factors including geometry, overall charge and substitution pattern of the complex. We also show that the two platinum(II)–salphen complexes developed as part of this series are emissive. Confocal microscopy studies were carried out with these two complexes using four different cell lines (CHO, HeLa, U2OS and HepG2). These studies showed that the cell permeability and localization are different for the two probes and highly dependent on the cell line used.