We report the label-free detection of single particles using photonic crystal nanobeam cavities fabricated in silicon-on-insulator platform, and embedded inside microfluidic channels fabricated in poly-dimethylsiloxane (PDMS). Our system operates in the telecommunication wavelength band, thus leveraging the widely available, robust and tunable telecom laser sources. Using this approach, we demonstrated the detection of polystyrene nanoparticles with dimensions down to 12.5nm in radius. Furthermore, binding events of a single streptavidin molecule have been observed.
Scalable microfabrication technology has enabled semiconductor and microelectronics industries, among other fields. Meanwhile, rapid and sensitive bio-molecule detection is increasingly important for drug discovery and biomedical diagnostics. In this work, we designed and demonstrated that photonic crystal sensor chips have high sensitivity for protein detection and can be mass-produced with scalable deep-UV lithography. We demonstrated label-free detection of carcinoembryonic antigen from pg/mL to μg/mL, with high quality factor photonic crystal nanobeam cavities.
The realization of efficient optical interfaces for solid-state atom-like systems is an important problem in quantum science with potential applications in quantum communications and quantum information processing. We describe and demonstrate a technique for coupling single nitrogen vacancy (NV) centers to suspended diamond photonic crystal cavities with quality factors up to 6000. Specifically, we present an enhancement of the NV center’s zero-phonon line fluorescence by a factor of ∼7 in low-temperature measurements.
Axonemes form the core of eukaryotic flagella and cilia, performing tasks ranging from transporting fluid in developing embryos to the propulsion of sperm. Despite their abundance across the eukaryotic domain, the mechanisms that regulate the beating action of axonemes remain unknown. The flagellar waveforms are 3D in general, but current understanding of how axoneme components interact stems from 2D data; comprehensive measurements of flagellar shape are beyond conventional microscopy. Moreover, current flagellar model systems (e.g., sea urchin, human sperm) contain accessory structures that impose mechanical constraints on movement, obscuring the "native" axoneme behavior. We address both problems by developing a high-speed holographic imaging scheme and applying it to the (male) microgametes of malaria (Plasmodium) parasites. These isolated flagella are a unique, mathematically tractable model system for the physics of microswimmers. We reveal the 3D flagellar waveforms of these microorganisms and map the differential shear between microtubules in their axonemes. Furthermore, we overturn claims that chirality in the structure of the axoneme governs the beat pattern [Hirokawa N, et al. (2009) Ann Rev Fluid Mech 41:53-72], because microgametes display a left- or right-handed character on alternate beats. This breaks the link between structural chirality in the axoneme and larger scale symmetry breaking (e.g., in developing embryos), leading us to conclude that accessory structures play a critical role in shaping the flagellar beat.
Spatial tailoring of the material constitutive properties is a well-known strategy to mold the local flow of given observables in different physical domains. Coordinate transformation-based methods (e.g., transformation optics) offer a powerful and systematic approach to design anisotropic, spatially-inhomogeneous artificial materials (“metamaterials”) capable of precisely manipulating wave-based (electromagnetic, acoustic, elastic) as well as diffusion-based (heat) phenomena in a desired fashion. However versatile these approaches have been, most designs have so far been limited to serving single-target functionalities in a given physical domain. Here we present a “transformation multi physics” framework that allows independent and simultaneous manipulation of multiple physical phenomena. As a proof of principle of this new scheme, we design and synthesize (in terms of realistic material constituents) a metamaterial shell that simultaneously behaves as a thermal concentrator and an electrical “invisibility cloak”. Our numerical results open up intriguing possibilities in the largely unexplored phase space of multi- functional metadevices, with a wide variety of potential applications to electrical, magnetic, acoustic, and thermal scenarios
Rowing is demanding, in part, because drag on the oars increases as the square of their speed. Hence, as muscles shorten faster, their force capacity falls, whereas drag rises. How do frogs resolve this dilemma to swim rapidly? We predicted that shortening velocity cannot exceed a terminal velocity where muscle and fluid torques balance. This terminal velocity, which is below Vmax, depends on gear ratio (GR ¼ outlever/inlever) and webbed foot area. Perhaps such properties of swimmers are ‘tuned’, enabling shortening speeds of approximately 0.3Vmax for maximal power. Predictions were tested using a ‘musculo-robotic’ Xenopus laevis foot driven either by a living in vitro or computational in silico plantaris longus muscle. Experiments verified predictions. Our principle finding is that GR ranges from 11.5 to 20 near the predicted optimum for rowing (GR 11). However, gearing influences muscle power more strongly than foot area. No single morphology is optimal for producing muscle power. Rather, the ‘optimal’ GR decreases with foot size, implying that rowing ability need not compromise jumping (and vice versa). Thus, despite our neglect of additional forces (e.g. added mass), our model predicts pairings of physiological and morphological properties to confer effective rowing. Beyond frogs, the model may apply across a range of size and complexity from aquatic insects to human-powered rowing.
Studies of the muscle force–velocity relationship and its derived n-shaped power–velocity curve offer important insights into muscular limits of performance. Given the power is maximal at 1/3 Vmax, geometric scaling of muscle force coupled with fluid drag force implies that this optimal muscle-shortening velocity for power cannot be maintained across the natural body-size range. Instead, muscle velocity may decrease with increasing body size, conferring a similar n-shaped power curve with body size. Here we examine swimming speed and muscle function in the aquatic frog Xenopus laevis. Swimming speed shows an n-shaped scaling relationship, peaking at 47.35 g. Further, in vitro muscle function of the ankle extensor plantaris longus also shows an optimal body mass for muscle power output (47.27 g), reflecting that of swimming speed. These findings suggest that in drag-based aquatic systems, muscle–environment interactions vary with body size, limiting both the muscle’s potential to produce power and the swimming speed.
We developed an on-chip microscale electroporation system that enables sequential delivery of multiple molecules with precise and independent dosage controllability into pre-selected identical populations of target cells. The ability to trap cells with uniform size distribution contributed to enhanced molecular delivery efficiency and cell viability. Additionally, the system provides real-time monitoring ability of the entire delivery process, allowing timely and independent modification of cell- and molecule-specific electroporation parameters. The precisely controlled amount of inherently membrane-impermeant molecules was transferred into human cancer cells by varying electric field strengths and molecule injection durations. The proposed microfluidic electroporation system's improved viability and comparable gene transfection efficiency to that of commercial systems suggest that the current system has great potential to expand the research fields that on-chip electroporation techniques can be used in.
In Drosophila, most individual olfactory receptor neurons (ORNs) project bilaterally to both sides of the brain. Having bilateral rather than unilateral projections may represent a useful redundancy. However, bilateral ORN projections to the brain should also compromise the ability to lateralize odours. Nevertheless, walking or flying Drosophila reportedly turn towards the antenna that is more strongly stimulated by odour. Here we show that each ORN spike releases approximately 40% more neurotransmitter from the axon branch ipsilateral to the soma than from the contralateral branch. As a result, when an odour activates the antennae asymmetrically, ipsilateral central neurons begin to spike a few milliseconds before contralateral neurons, and at a 30to50% higher rate than contralateral neurons. We show that a walking fly can detect a 5% asymmetry in total ORN input to its left and right antennal lobes, and can turn towards the odour in less time than it requires the fly to complete a stride. These results demonstrate that neurotransmitter release properties can be tuned independently at output synapses formed by a single axon onto two target cells with identical functions and morphologies. Our data also show that small differences in spike timing and spike rate can produce reliable differences in olfactory behaviour.
Imaging fluorescence in moving cells is fundamentally challenging because the exposure time is constrained by motion-blur, which limits the available signal. We report a method to image fluorescently labeled leukemia cells in fluid flow that has an effective exposure time of up to 50 times the motion-blur limit. Flowing cells are illuminated with a pseudo-random excitation pulse sequence, resulting in a motion-blur that can be computationally removed to produce near diffraction-limited images. This method enables observation of cellular organelles and their behavior in a fluid environment that resembles the vasculature.