Migration speed of captured breast cancer subpopulations correlates with metastatic fitness.

The genetic alterations contributing to migration proficiency, a phenotypic hallmark of metastatic cells required for colonizing distant organs, remain poorly defined. Here, we used single-cell magneto-optical capture (scMOCa) to isolate fast cells from heterogeneous human breast cancer cell populations, based on their migratory ability alone. We show that captured fast cell subpopulations retain higher migration speed and focal adhesion dynamics over many generations as a result of a motility-related transcriptomic profile. Upregulated genes in isolated fast cells encoded integrin subunits, proto-cadherins and numerous other genes associated with cell migration. Dysregulation of several of these genes correlates with poor survival outcomes in people with breast cancer, and primary tumors established from fast cells generated a higher number of circulating tumor cells and soft tissue metastases in pre-clinical mouse models. Subpopulations of cells selected for a highly migratory phenotype demonstrated an increased fitness for metastasis.

Curcuma longa-Based Optical Sensor for Hydrochloric Acid and Ammonia Vapor Detection.

In this research, we present a prototype optical system that offers significant advances in detecting hydrochloric acid (HCl) and ammonia (NH3) vapors. The system utilizes a natural pigment sensor based on Curcuma longa that is securely attached to a glass surface support. Through extensive development and testing with HCl (37% aqueous solution) and NH3 (29% aqueous solution) solutions, we have successfully demonstrated the effectiveness of our sensor. To facilitate the detection process, we have developed an injection system that exposes C. longa pigment films to the targeted vapors. The interaction between the vapors and the pigment films triggers a distinct color change, which is then analyzed by the detection system. By capturing the transmission spectra of the pigment film, our system allows a precise comparison of these spectra at different concentrations of the vapors. Our proposed sensor exhibits remarkable sensitivity, allowing the detection of HCl at a concentration of 0.009 ppm using only 100 µL (2.3 mg) of pigment film. In addition, it can detect NH3 at a concentration of 0.03 ppm with a 400 µL (9.2 mg) pigment film. Integrating C. longa as a natural pigment sensor in an optical system opens up new possibilities for detecting hazardous gases. The simplicity and efficiency of our system, combined with its sensitivity, make it an attractive tool in environmental monitoring and industrial safety applications.

Chlorophyll-a Pigment Measurement of Spirulina in Algal Growth Monitoring Using Portable Pulsed LED Fluorescence Lidar System.

Chlorophyll-a measurement is important in algal growth and water quality monitoring in natural waters. A portable pulsed LED fluorescence lidar system based on the preliminary algal organic matter and pigments excitation-emission matrix (EEM) of commercialized AZTEC Spirulina powder at varying concentrations was developed. Fluorescence peaks from EEMs showed increasing intensity as the Spirulina concentration increases. Using this information, an LED fluorescence lidar with a wavelength of 385 nm, pulse width of 10 ns, and repetition frequency of 500 kHz was constructed for chlorophyll detection at 680 nm. Turbidity measurements were also conducted at 700 nm emission wavelength at the same excitation wavelength. Range-resolved fluorescence lidar signals from the portable pulsed LED fluorescence lidar system are highly correlated with the standard methods such as optical density at 680 nm (R2 = 0.87), EEM fluorescence chlorophyll-a pigment at 680 nm (R2 = 0.89), and corrected chlorophyll-a concentration (R2 =0.92). The F680/F700 lidar ratio was measured to provide a linear relationship of chlorophyll-a and turbidity in waters. The F680/F700 measurement showed strong correlations with Spirulina concentration (R2 = 0.94), absorbance at 680 nm (R2 = 0.84), EEM chlorophyll-a pigment at 680 nm (R2 = 0.83), and corrected chlorophyll-a concentration (R2 = 0.86). Results revealed that this new technique of chlorophyll-a measurement can be used as an alternative to other standard methods in algal growth monitoring.

In vivo nonlinear imaging of corneal structures with special focus on BALB/c and streptozotocin-diabetic Thy1-YFP mice.

Two-photon microscopy (TPM) allows high contrast imaging at a subcellular resolution scale. In this work, the microscopy technique was applied to visualize corneal structures in two mouse models (BALB/c and B6.Cg-Tg(Thy1-YFP)16Jrs/J) in vivo. In particular, the transgenic Thy1-YFP mice expressing the yellow fluorescent protein (YFP) in all motor and sensory neurons had been used for investigating the nerve fiber density in healthy and streptozotocin-diabetic mice. This model is clinically relevant since patients suffering from diabetes mellitus have a high risk to develop small fiber neuropathy. Nonlinear laser scanning microscopy displayed a reduction of nerve fiber density in streptozotocin-diabetic versus healthy mice and confirmed data obtained by confocal laser scanning microscopy (CLSM). In recent years, corneal CLSM was proved to be an appropriate non-invasive tool for an early diagnosis of diabetic neuropathy. Nevertheless, validation of the CLSM method for the clinical routine is currently a matter of investigation and requires confirmation by further studies and complementary techniques. Thus, the present study provides further evidence of corneal confocal microscopy as a promising technique for non-invasive detection of diabetic neuropathy. Information derived from these experiments may become clinically relevant and help to develop new drugs for treatment of diabetic neuropathy.

Fiber-based quantum-dot pulse oximetry for wearable health monitoring with high wavelength selectivity and photoplethysmogram sensitivity.

Increasing demand for real-time healthcare monitoring is leading to advances in thin and flexible optoelectronic device-based wearable pulse oximetry. Most previous studies have used OLEDs for this purpose, but did not consider the side effects of broad full-width half-maximum (FWHM) characteristics and single substrates. In this study, we performed SpO2 measurement using a fiber-based quantum-dot pulse oximetry (FQPO) system capable of mass production with a transferable encapsulation technique, and a narrow FWHM of about 30 nm. Based on analyses we determined that uniform angular narrow FWHM-based light sources are important for accurate SpO2 measurements through multi-layer structures and human skin tissues. The FQPO was shown to have improved photoplethysmogram (PPG) signal sensitivity with no waveguide-mode noise signal, as is typically generated when using a single substrate (30-50%). We successfully demonstrate improved SpO2 measurement accuracy as well as all-in-one clothing-type pulse oximetry with FQPO.

Resource-efficient fault-tolerant one-way quantum repeater with code concatenation.

One-way quantum repeaters where loss and operational errors are counteracted by quantum error-correcting codes can ensure fast and reliable qubit transmission in quantum networks. It is crucial that the resource requirements of such repeaters, for example, the number of qubits per repeater node and the complexity of the quantum error-correcting operations are kept to a minimum to allow for near-future implementations. To this end, we propose a one-way quantum repeater that targets both the loss and operational error rates in a communication channel in a resource-efficient manner using code concatenation. Specifically, we consider a tree-cluster code as an inner loss-tolerant code concatenated with an outer 5-qubit code for protection against Pauli errors. Adopting flag-based stabilizer measurements, we show that intercontinental distances of up to 10,000 km can be bridged with a minimized resource overhead by interspersing repeater nodes that each specialize in suppressing either loss or operational errors. Our work demonstrates how tailored error-correcting codes can significantly lower the experimental requirements for long-distance quantum communication.

Unveiling Hidden Prints: Optically stimulated luminescence for latent fingerprint detection.

Fluorescent lighting and optical techniques have been widely utilized to enhance the detection of latent fingerprints. However, the development of new techniques is imperative to expand the range of surfaces from which latent fingerprints can be detected. When relying on traditional methods, fingerprint evidence can remain undetected or even disregarded due to insufficient detection and limited detail, especially when dealing with a luminescent background. In this study, we propose the utilization of optically stimulated luminescence (OSL) applied to a Ba2SiO4 matrix, co-doped with Eu2+ and Dy3+, as a powerful method for visualizing latent fingerprints on various surfaces, including thin plastic bags, rigid duct tape, thin aluminum foil, and glass slices. This technique effectively eliminates any luminescent background and significantly enhances optical imaging. This represents the first successful application of OSL in the development of latent fingerprints, thus paving the way for more efficient and effective forensic techniques in the future.

Fast histological assessment of adipose tissue inflammation by label-free mid-infrared optoacoustic microscopy.

Conventional histology, as well as immunohistochemistry or immunofluorescence, enables the study of morphological and phenotypical changes during tissue inflammation with single-cell accuracy. However, although highly specific, such techniques require multiple time-consuming steps to apply exogenous labels, which might result in morphological deviations from native tissue structures. Unlike these techniques, mid-infrared (mid-IR) microspectroscopy is a label-free optical imaging method that retrieves endogenous biomolecular contrast without altering the native composition of the samples. Nevertheless, due to the strong optical absorption of water in biological tissues, conventional mid-IR microspectroscopy has been limited to dried thin (5-10 µm) tissue preparations and, thus, it also requires time-consuming steps-comparable to conventional imaging techniques. Here, as a step towards label-free analytical histology of unprocessed tissues, we applied mid-IR optoacoustic microscopy (MiROM) to retrieve intrinsic molecular contrast by vibrational excitation and, simultaneously, to overcome water-tissue opacity of conventional mid-IR imaging in thick (mm range) tissues. In this proof-of-concept study, we demonstrated application of MiROM for the fast, label-free, non-destructive assessment of the hallmarks of inflammation in excised white adipose tissue; i.e., formation of crown-like structures and changes in adipocyte morphology.

Widely accessible method for 3D microflow mapping at high spatial and temporal resolutions.

Advances in microfluidic technologies rely on engineered 3D flow patterns to manipulate samples at the microscale. However, current methods for mapping flows only provide limited 3D and temporal resolutions or require highly specialized optical set-ups. Here, we present a simple defocusing approach based on brightfield microscopy and open-source software to map micro-flows in 3D at high spatial and temporal resolution. Our workflow is both integrated in ImageJ and modular. We track seed particles in 2D before classifying their Z-position using a reference library. We compare the performance of a traditional cross-correlation method and a deep learning model in performing the classification step. We validate our method on three highly relevant microfluidic examples: a channel step expansion and displacement structures as single-phase flow examples, and droplet microfluidics as a two-phase flow example. First, we elucidate how displacement structures efficiently shift large particles across streamlines. Second, we reveal novel recirculation structures and folding patterns in the internal flow of microfluidic droplets. Our simple and widely accessible brightfield technique generates high-resolution flow maps and it will address the increasing demand for controlling fluids at the microscale by supporting the efficient design of novel microfluidic structures.

Wafer-level vapor cells filled with laser-actuated hermetic seals for integrated atomic devices.

Atomic devices such as atomic clocks and optically-pumped magnetometers rely on the interrogation of atoms contained in a cell whose inner content has to meet high standards of purity and accuracy. Glass-blowing techniques and craftsmanship have evolved over many decades to achieve such standards in macroscopic vapor cells. With the emergence of chip-scale atomic devices, the need for miniaturization and mass fabrication has led to the adoption of microfabrication techniques to make millimeter-scale vapor cells. However, many shortcomings remain and no process has been able to match the quality and versatility of glass-blown cells. Here, we introduce a novel approach to structure, fill and seal microfabricated vapor cells inspired from the century-old approach of glass-blowing, through opening and closing single-use zero-leak microfabricated valves. These valves are actuated exclusively by laser, and operate in the same way as the "make-seals" and "break-seals" found in the filling apparatus of traditional cells. Such structures are employed to fill cesium vapor cells at the wafer-level. The make-seal structure consists of a glass membrane that can be locally heated and deflected to seal a microchannel. The break-seal is obtained by breaching a silicon wall between cavities. This new approach allows adapting processes previously restricted to glass-blown cells. It can also be extended to vacuum microelectronics and vacuum-packaging of micro-electro-mechanical systems (MEMS) devices.

Immersion graded index optics: theory, design, and prototypes.

Immersion optics enable creation of systems with improved optical concentration and coupling by taking advantage of the fact that the luminance of light is proportional to the square of the refractive index in a lossless optical system. Immersion graded index optical concentrators, that do not need to track the source, are described in terms of theory, simulations, and experiments. We introduce a generalized design guide equation which follows the Pareto function and can be used to create various immersion graded index optics depending on the application requirements of concentration, refractive index, height, and efficiency. We present glass and polymer fabrication techniques for creating broadband transparent graded index materials with large refractive index ranges, (refractive index ratio)2 of ~2, going many fold beyond what is seen in nature or the optics industry. The prototypes demonstrate 3x optical concentration with over 90% efficiency. We report via functional prototypes that graded-index-lens concentrators perform close to the theoretical maximum limit and we introduce simple, inexpensive, design-flexible, and scalable fabrication techniques for their implementation.

Effect of inoculum size and antibiotics on bacterial traveling bands in a thin microchannel defined by optical adhesive.

Phenotypic diversity in bacterial flagella-induced motility leads to complex collective swimming patterns, appearing as traveling bands with transient locally enhanced cell densities. Traveling bands are known to be a bacterial chemotactic response to self-generated nutrient gradients during growth in resource-limited microenvironments. In this work, we studied different parameters of Escherichia coli (E. coli) collective migration, in particular the quantity of bacteria introduced initially in a microfluidic chip (inoculum size) and their exposure to antibiotics (ampicillin, ciprofloxacin, and gentamicin). We developed a hybrid polymer-glass chip with an intermediate optical adhesive layer featuring the microfluidic channel, enabling high-content imaging of the migration dynamics in a single bacterial layer, i.e., bacteria are confined in a quasi-2D space that is fully observable with a high-magnification microscope objective. On-chip bacterial motility and traveling band analysis was performed based on individual bacterial trajectories by means of custom-developed algorithms. Quantifications of swimming speed, tumble bias and effective diffusion properties allowed the assessment of phenotypic heterogeneity, resulting in variations in transient cell density distributions and swimming performance. We found that incubation of isogeneic E. coli with different inoculum sizes eventually generated different swimming phenotype distributions. Interestingly, incubation with antimicrobials promoted bacterial chemotaxis in specific cases, despite growth inhibition. Moreover, E. coli filamentation in the presence of antibiotics was assessed, and the impact on motility was evaluated. We propose that the observation of traveling bands can be explored as an alternative for fast antimicrobial susceptibility testing.

Methods for latent image simulations in photolithography with a polychromatic light attenuation equation for fabricating VIAs in 2.5D and 3D advanced packaging architectures.

As demand accelerates for multifunctional devices with a small footprint and minimal power consumption, 2.5D and 3D advanced packaging architectures have emerged as an essential solution that use through-substrate vias (TSVs) as vertical interconnects. Vertical stacking enables chip packages with increased functionality, enhanced design versatility, minimal power loss, reduced footprint and high bandwidth. Unlocking the potential of photolithography for vertical interconnect access (VIA) fabrication requires fast and accurate predictive modeling of diffraction effects and resist film photochemistry. This procedure is especially challenging for broad-spectrum exposure systems that use, for example, Hg bulbs with g-, h-, and i-line UV radiation. In this paper, we present new methods and equations for VIA latent image determination in photolithography that are suitable for broad-spectrum exposure and negate the need for complex and time-consuming in situ metrology. Our technique is accurate, converges quickly on the average modern PC and could be readily integrated into photolithography simulation software. We derive a polychromatic light attenuation equation from the Beer-Lambert law, which can be used in a critical exposure dose model to determine the photochemical reaction state. We integrate this equation with an exact scalar diffraction formula to produce a succinct equation comprising a complete coupling between light propagation phenomena and photochemical behavior. We then perform a comparative study between 2D/3D photoresist latent image simulation geometries and directly corresponding experimental data, which demonstrates a highly positive correlation. We anticipate that this technique will be a valuable asset to photolithography, micro- and nano-optical systems and advanced packaging/system integration with applications in technology domains ranging from space to automotive to the Internet of Things (IoT).

Efficient full-path optical calculation of scalar and vector diffraction using the Bluestein method.

Efficient calculation of the light diffraction in free space is of great significance for tracing electromagnetic field propagation and predicting the performance of optical systems such as microscopy, photolithography, and manipulation. However, existing calculation methods suffer from low computational efficiency and poor flexibility. Here, we present a fast and flexible calculation method for computing scalar and vector diffraction in the corresponding optical regimes using the Bluestein method. The computation time can be substantially reduced to the sub-second level, which is 105 faster than that achieved by the direct integration approach (~hours level) and 102 faster than that achieved by the fast Fourier transform method (~minutes level). The high efficiency facilitates the ultrafast evaluation of light propagation in diverse optical systems. Furthermore, the region of interest and the sampling numbers can be arbitrarily chosen, endowing the proposed method with superior flexibility. Based on these results, full-path calculation of a complex optical system is readily demonstrated and verified by experimental results, laying a foundation for real-time light field analysis for realistic optical implementation such as imaging, laser processing, and optical manipulation.

Infrared neural stimulation and inhibition using an implantable silicon photonic microdevice.

Brain is one of the most temperature sensitive organs. Besides the fundamental role of temperature in cellular metabolism, thermal response of neuronal populations is also significant during the evolution of various neurodegenerative diseases. For such critical environmental factor, thorough mapping of cellular response to variations in temperature is desired in the living brain. So far, limited efforts have been made to create complex devices that are able to modulate temperature, and concurrently record multiple features of the stimulated region. In our work, the in vivo application of a multimodal photonic neural probe is demonstrated. Optical, thermal, and electrophysiological functions are monolithically integrated in a single device. The system facilitates spatial and temporal control of temperature distribution at high precision in the deep brain tissue through an embedded infrared waveguide, while it provides recording of the artefact-free electrical response of individual cells at multiple locations along the probe shaft. Spatial distribution of the optically induced temperature changes is evaluated through in vitro measurements and a validated multi-physical model. The operation of the multimodal microdevice is demonstrated in the rat neocortex and in the hippocampus to increase or suppress firing rate of stimulated neurons in a reversible manner using continuous wave infrared light (λ = 1550 nm). Our approach is envisioned to be a promising candidate as an advanced experimental toolset to reveal thermally evoked responses in the deep neural tissue.

Learning to synthesize: robust phase retrieval at low photon counts.

The quality of inverse problem solutions obtained through deep learning is limited by the nature of the priors learned from examples presented during the training phase. Particularly in the case of quantitative phase retrieval, spatial frequencies that are underrepresented in the training database, most often at the high band, tend to be suppressed in the reconstruction. Ad hoc solutions have been proposed, such as pre-amplifying the high spatial frequencies in the examples; however, while that strategy improves the resolution, it also leads to high-frequency artefacts, as well as low-frequency distortions in the reconstructions. Here, we present a new approach that learns separately how to handle the two frequency bands, low and high, and learns how to synthesize these two bands into full-band reconstructions. We show that this "learning to synthesize" (LS) method yields phase reconstructions of high spatial resolution and without artefacts and that it is resilient to high-noise conditions, e.g., in the case of very low photon flux. In addition to the problem of quantitative phase retrieval, the LS method is applicable, in principle, to any inverse problem where the forward operator treats different frequency bands unevenly, i.e., is ill-posed.

A Trojan Horse for live-cell super-resolution microscopy.

New peptide vehicles enable the efficient live-cell labeling of intracellular organelles with cell-impermeable fluorescent probes by simple coincubation, paving the way for refined multicolor super-resolution fluorescence imaging.

Erratum: Author Correction: Simple and efficient delivery of cell-impermeable organic fluorescent probes into live cells for live-cell superresolution imaging.

[This corrects the article DOI: 10.1038/s41377-019-0188-0.].

Carrier-assisted differential detection.

To overcome power fading induced by chromatic dispersion in optical fiber communications, optical field recovery is a promising solution for direct detection short-reach applications, such as fast-evolving data center interconnects (DCIs). To date, various direct detection schemes capable of optical field recovery have been proposed, including Kramers-Kronig (KK) and signal-signal beat interference (SSBI) iterative cancellation (IC) receivers. However, they are all restricted to the single sideband (SSB) modulation format, thus conspicuously losing half of the electrical spectral efficiency (SE) compared with double sideband (DSB) modulation. Additionally, SSB suffers from the noise folding issue, requiring a precise optical filter that complicates the receiver design. As such, it is highly desirable to investigate the field recovery of DSB signals via direct detection. In this paper, for the first time, we propose a novel receiver scheme called carrier-assisted differential detection (CADD) to realize optical field recovery of complex-valued DSB signals via direct detection. First, CADD doubles the electrical SE compared with the KK and SSBI IC receivers by adopting DSB modulation without sacrificing receiver sensitivities. Furthermore, by using direct detection without needing a precise receiver optical filter, CADD can employ cost-effective uncooled lasers as opposed to expensive temperature-controlled lasers in coherent systems. Our proposed receiver architecture opens a new class of direct detection schemes that are suitable for photonic integration analogous to homodyne receivers in coherent detection.

Opto-thermoelectric microswimmers.

Inspired by the "run-and-tumble" behaviours of Escherichia coli (E. coli) cells, we develop opto-thermoelectric microswimmers. The microswimmers are based on dielectric-Au Janus particles driven by a self-sustained electrical field that arises from the asymmetric optothermal response of the particles. Upon illumination by a defocused laser beam, the Janus particles exhibit an optically generated temperature gradient along the particle surfaces, leading to an opto-thermoelectrical field that propels the particles. We further discover that the swimming direction is determined by the particle orientation. To enable navigation of the swimmers, we propose a new optomechanical approach to drive the in-plane rotation of Janus particles under a temperature-gradient-induced electrical field using a focused laser beam. Timing the rotation laser beam allows us to position the particles at any desired orientation and thus to actively control the swimming direction with high efficiency. By incorporating dark-field optical imaging and a feedback control algorithm, we achieve automated propelling and navigation of the microswimmers. Our opto-thermoelectric microswimmers could find applications in the study of opto-thermoelectrical coupling in dynamic colloidal systems, active matter, biomedical sensing, and targeted drug delivery.