Synthesis and Characterization of Superparamagnetic Iron Oxide Nanoparticles: A Series of Laboratory Experiments.

The following laboratory procedure provides students with hands-on experience in nanomaterial chemistry and characterization. This three-day protocol is easy to follow for undergraduates with basic chemistry or materials science backgrounds and is suitable for inclusion in upper-division courses in inorganic chemistry or materials science. Students use air-free chemistry procedures to synthesize and separate iron oxide magnetic nanoparticles and subsequently modify the nanoparticle surface by using a chemical stripping agent. The morphology and chemical composition of the nanoparticles are characterized using electron microscopy and dynamic light scattering measurements. Additionally, magnetic characterization of the particles is performed using an inexpensive open-source (3D-printed) magnetophotometer. Possible modifications to the synthesis procedure, including the incorporation of dopants to modify the magnetic response and alternative characterization techniques, are discussed. The three-day synthesis, purification, and characterization laboratory will prepare students with crucial skills for advanced technology industries such as semiconductor manufacturing, nanomedicine, and green chemistry.

Dielectric optical waveguide fabricated on a transparent substrate.

Transparent glass substrates are routinely used in the fabrication of metasurfaces, augmented reality (AR), virtual reality (VR), and holographic devices. While readily compatible with photolithographic patterning methods, when electron beam (E-Beam) techniques are used, field distortion and stitching errors can result due to the buildup of charge. A common approach to overcome this issue is to deposit a thin conductive polymer layer (E-Spacer). However, if high-voltage E-Beam is used to achieve nano-features, the polymer conductivity is not sufficient. We have shown that by using chromium (Cr) as an overcoating conductive layer on the resist, we can achieve accurate and seamless patterning in multiple writing fields and used the method to fabricate on-chip Si3N4 waveguides on SiO2. This technique has the potential to enable the fabrication of large-scale integrated photonic systems on transparent or dielectric substrates.

Stretchable optical diffraction grating from poly(acrylic acid)/polyethylene oxide stereocomplex.

Advances in optical materials, which were initially static elements, have enabled dynamically tunable optical diffraction gratings to be designed. One common tuning strategy relies on mechanical deformation of the grating pitch to modify the diffraction pattern. In the present work, we demonstrate an all-polymer tunable diffraction grating fabricated using a modified replica molding process. The poly(acrylic acid) (PAA)/polyethylene oxide (PEO) polymer stereocomplex films exhibit optical transmittance at or above 80% from 500 nm to 1400 nm and stretchability over 800% strain with reversibility under 70% strain. The imprinted gratings are characterized at 633 nm and 1064 nm under a range of strain conditions. The measured tunability agrees with finite element method modeling.

All-optical reversible control of integrated resonant cavity by a self-assembled azobenzene monolayer.

The next frontier in photonics will rely on the synergistic combination of disparate material systems. One unique organic molecule is azobenzene. This molecule can reversibly change conformations when optically excited in the blue (trans-to-cis) or mid-IR (cis-to-trans). Here, we form an oriented monolayer of azobenzene-containing 4-(4-diethylaminophenylazo)pyridine (Aazo) on SiO2 optical resonators. Due to the uniformity of the Aazo layers, quality factors over 106 are achieved. To control the photo-response, the density of Aazo groups is tuned by integrating methyl spacer molecules. Using a pair of lasers, the molecule is reversibly flipped between molecular conformations, inducing a refractive index change which results in a resonant wavelength shift. The magnitude of the shift scales with the relative surface density of Aazo. To investigate reproducibility and stability of the organic monolayer, three switching cycles are demonstrated, and the performance is consistent even after a device is stored in air for 6 months.

Cascaded Stokes and anti-Stokes laser based on an optical resonator with a self-assembled organic monolayer.

Due to their high circulating intensities, ultra-high quality factor dielectric whispering gallery mode resonators have enabled the development of low threshold Raman microlasers. Subsequently, other Raman-related phenomena, such as cascaded stimulated Raman scattering (CSRS) and stimulated anti-Stokes Raman scattering (SARS), were observed. While low threshold frequency conversion and generation have clear applications, CSRS and SARS have been limited by the low Raman gain. In this work, the surface of a silica resonator is modified with an organic monolayer, increasing the Raman gain. Up to four orders of CSRS are observed with sub-milliwatt (mW) input power, and the SARS efficiency is improved by three orders of magnitude compared to previous studies with hybrid resonators.

Raman-Kerr frequency combs in Zr-doped silica hybrid microresonators.

Resonant cavity-enhanced Kerr frequency combs have been demonstrated using a range of cavity materials. Regardless of cavity type, one fundamental challenge is achieving low or flat dispersion while maintaining high-efficiency four-wave mixing (FWM). Here we demonstrate a Raman-Kerr frequency comb using a Zr-doped silica hybrid toroidal microcavity. The Zr-doped layer both flattens the dispersion and increases the stimulated Raman scattering efficiency. This enhancement enables the generation of FWM around both the Stokes and anti-Stokes Raman scattering emissions. As a result, the Raman-Kerr frequency comb spans more than 300 nm in the near-IR region with less than 5.2 mW of input power.

Quantifying pulsed electric field-induced membrane nanoporation in single cells.

Plasma membrane disruption can trigger a host of cellular activities. One commonly observed type of disruption is pore formation. Molecular dynamic (MD) simulations of simplified lipid membrane structures predict that controllably disrupting the membrane via nano-scale poration may be possible with nanosecond pulsed electric fields (nsPEF). Until recently, researchers hoping to verify this hypothesis experimentally have been limited to measuring the relatively slow process of fluorescent markers diffusing across the membrane, which is indirect evidence of nanoporation that could be channel-mediated. Leveraging recent advances in nonlinear optical microscopy, we elucidate the role of pulse parameters in nsPEF-induced membrane permeabilization in live cells. Unlike previous techniques, it is able to directly observe loss of membrane order at the onset of the pulse. We also develop a complementary theoretical model that relates increasing membrane permeabilization to membrane pore density. Due to the significantly improved spatial and temporal resolution possible with our imaging method, we are able to directly compare our experimental and theoretical results. Their agreement provides substantial evidence that nanoporation does occur and that its development is dictated by the electric field distribution.

Flexible Light-Emitting Nanocomposite Based on ZnO Nanotetrapods.

Flexible, light-emitting materials have shown promise in a wide range of applications. Here, we develop an inverse soft-lithography process for embedding zinc oxide nanotetrapods (ZnO NTP) uniformly and nondestructively into a host matrix. The crystalline NTPs were synthesized using a catalyst-free, environmentally friendly chemical vapor transport method. The fluorescent emission of the ZnO NTPs was measured before and after the embedding process. Cyclical mechanical bend tests (N > 100) were performed. The emission of the nanomaterial remains throughout.

On-chip asymmetric microcavity optomechanics.

High quality factor (Q) optical resonators have enabled rapid growth in the field of cavity-enhanced, radiation pressure-induced optomechanics. However, because research has focused on axisymmetric devices, the observed regenerative excited mechanical modes are similar. In the present work, a strategy for fabricating high-Q whispering gallery mode microcavities with varying degrees of asymmetry is developed and demonstrated. Due to the combination of high optical Q and asymmetric device design, two previously unobserved modes, the asymmetric cantilever and asymmetric crown mode, are demonstrated with sub-mW thresholds for onset of oscillations. The experimental results are in good agreement with computational modeling predictions.

Temperature sensor based on a hybrid ITO-silica resonant cavity.

Integrated optical devices comprised of multiple material systems are able to achieve unique performance characteristics, enabling applications in sensing and in telecommunications. Due to ease of fabrication, the majority of previous work has focused on polymer-dielectric or polymer-semiconductor systems. However, the environmental stability of polymers is limited. In the present work, a hybrid device comprised of an indium tin oxide (ITO) coating on a silicon dioxide toroidal resonant cavity is fabricated. Finite element method simulations of the optical field in the multi-material device are performed, and the optical mode profile is significantly altered by the high index film. The quality factor is also measured and is material loss limited. Additionally, its performance as a temperature sensor is characterized. Due to the high thermo-optic coefficient of ITO and the localization of the optical field in the ITO layer, the hybrid temperature sensor demonstrates a nearly 3-fold improvement in performance over the conventional silica device.

Label-free, single molecule resonant cavity detection: a double-blind experimental study.

Optical resonant cavity sensors are gaining increasing interest as a potential diagnostic method for a range of applications, including medical prognostics and environmental monitoring. However, the majority of detection demonstrations to date have involved identifying a "known" analyte, and the more rigorous double-blind experiment, in which the experimenter must identify unknown solutions, has yet to be performed. This scenario is more representative of a real-world situation. Therefore, before these devices can truly transition, it is necessary to demonstrate this level of robustness. By combining a recently developed surface chemistry with integrated silica optical sensors, we have performed a double-blind experiment to identify four unknown solutions. The four unknown solutions represented a subset or complete set of four known solutions; as such, there were 256 possible combinations. Based on the single molecule detection signal, we correctly identified all solutions. In addition, as part of this work, we developed noise reduction algorithms.

Photoelastic ultrasound detection using ultra-high-Q silica optical resonators.

As a result of its non-invasive and non-destructive nature, ultrasound imaging has found a variety of applications in a wide range of fields, including healthcare and electronics. One accurate and sensitive approach for detecting ultrasound waves is based on optical microcavities. Previous research using polymer microring resonators demonstrated detection based on the deformation of the cavity induced by the ultrasound wave. An alternative detection approach is based on the photoelastic effect in which the ultrasound wave induces a strain in the material that is converted to a refractive index change. In the present work, photoelastic-based ultrasound detection is experimentally demonstrated using ultra high quality factor silica optical microcavities. As a result of the increase in Q and in coupled power, the noise equivalent pressure is reduced, and the device response is increased. A finite element method model that includes both the acoustics and optics components of this system is developed, and the predictive accuracy of the model is determined.

Titanium-enhanced Raman microcavity laser.

Whispering gallery mode microcavities are ideally suited to form microlaser devices because the high circulating intensity within the cavity results in ultralow lasing thresholds. However, to achieve low-threshold Raman lasing in silica devices, it is necessary to have quality factors above 100 million. One approach to circumvent this restriction is to intercalate a sensitizer into the silica, which increases the Raman gain. In the present work, we demonstrate a Raman laser based on a titanium sensitized silica solgel coated toroidal microcavity. By tuning the concentration of the Ti, the Raman efficiency improves over 3× while maintaining sub-mW thresholds.

Hybrid integrated label-free chemical and biological sensors.

Label-free sensors based on electrical, mechanical and optical transduction methods have potential applications in numerous areas of society, ranging from healthcare to environmental monitoring. Initial research in the field focused on the development and optimization of various sensor platforms fabricated from a single material system, such as fiber-based optical sensors and silicon nanowire-based electrical sensors. However, more recent research efforts have explored designing sensors fabricated from multiple materials. For example, synthetic materials and/or biomaterials can also be added to the sensor to improve its response toward analytes of interest. By leveraging the properties of the different material systems, these hybrid sensing devices can have significantly improved performance over their single-material counterparts (better sensitivity, specificity, signal to noise, and/or detection limits). This review will briefly discuss some of the methods for creating these multi-material sensor platforms and the advances enabled by this design approach.

Gold nanorod plasmonic upconversion microlaser.

Plasmonic-photonic interactions have stimulated significant interdisciplinary interest, leading to rapid innovations in solar design and biosensors. However, the development of an optically pumped plasmonic laser has failed to keep pace due to the difficulty of integrating a plasmonic gain material with a suitable pump source. In the present work, we develop a method for coating high quality factor toroidal optical cavities with gold nanorods, forming a photonic-plasmonic laser. By leveraging the two-photon upconversion capability of the nanorods, lasing at 581 nm with a 20 µW threshold is demonstrated.

Detecting Disruption of HER2 Membrane Protein Organization in Cell Membranes with Nanoscale Precision.

The spatiotemporal organization of proteins within the cell membrane can affect numerous biological functions, including cell signaling, communication, and transportation. Deviations from normal spatial arrangements have been observed in various diseases, and a better understanding of this process is a key stepping stone to advancing development of clinical interventions. However, given the nanometer length scales involved, detecting these subtle changes has primarily relied on complex super-resolution and single-molecule imaging methods. In this work, we demonstrate an alternative fluorescent imaging strategy for detecting protein organization based on a material that exhibits a unique photophysical behavior known as aggregation-induced emission (AIE). Organic AIE molecules have an increase in emission signal when they are in close proximity, and the molecular motion is restricted. This property simultaneously addresses the high background noise and low detection signal that limit conventional widefield fluorescent imaging. To demonstrate the potential of this approach, the fluorescent molecule sensor is conjugated to a human epidermal growth factor receptor 2 (HER2)-specific antibody and used to investigate the spatiotemporal behavior of HER2 clustering in the membrane of HER2-overexpressing breast cancer cells. Notably, the disruption of HER2 clusters in response to an FDA-approved monoclonal antibody therapeutic (Trastuzumab) is successfully detected using a simple widefield fluorescent microscope. While the sensor demonstrated here is optimized for sensing HER2 clustering, it is an easily adaptable platform. Moreover, given the compatibility with widefield imaging, the system has the potential to be used with high-throughput imaging techniques, accelerating investigations into membrane protein spatiotemporal organization.

Nondestructive, quantitative viability analysis of 3D tissue cultures using machine learning image segmentation.

Ascertaining the collective viability of cells in different cell culture conditions has typically relied on averaging colorimetric indicators and is often reported out in simple binary readouts. Recent research has combined viability assessment techniques with image-based deep-learning models to automate the characterization of cellular properties. However, further development of viability measurements to assess the continuity of possible cellular states and responses to perturbation across cell culture conditions is needed. In this work, we demonstrate an image processing algorithm for quantifying features associated with cellular viability in 3D cultures without the need for assay-based indicators. We show that our algorithm performs similarly to a pair of human experts in whole-well images over a range of days and culture matrix compositions. To demonstrate potential utility, we perform a longitudinal study investigating the impact of a known therapeutic on pancreatic cancer spheroids. Using images taken with a high content imaging system, the algorithm successfully tracks viability at the individual spheroid and whole-well level. The method we propose reduces analysis time by 97% in comparison with the experts. Because the method is independent of the microscope or imaging system used, this approach lays the foundation for accelerating progress in and for improving the robustness and reproducibility of 3D culture analysis across biological and clinical research.

Silica microtoroid resonator sensor with monolithically integrated waveguides.

Due to their wide operating range, silica toroidal whispering gallery mode microresonators have enabled numerous applications from fundamental physics to lasing and sensing. However, the integration of a waveguide with these microresonators has not been achieved which limits their integration with additional on-chip components. Here, we demonstrate a novel approach for monolithically integrating a silica microtoroid with an on-chip waveguide to form a fully integrated microtoroid-waveguide system with quality factors in excess of 4 million. Similar to the conventional toroidal cavities, power-independent operation is demonstrated. UV and temperature sensing experiments are also performed using the monolithically integrated microtoroid-waveguide system.

Optimal design of suspended silica on-chip splitter.

Photonic splitters and couplers are one of the fundamental elements in integrated optical circuits. As such, over the past decade significant research efforts have been dedicated to the development of low loss, wide bandwidth devices. While silica-based devices have clear advantages in terms of bandwidth, silicon and silicon nitride devices have lead the field in terms of ease of integration. In the present work, we provide design parameters for a novel splitter based on a suspended silica device. Unlike previous coupler devices which have smooth transition regions, the proposed device has a small defect which enables coupling across a large membrane. The designs are based on 3D FDTD models, and incorporate wavelength, refractive index and polarization dependence. The model is experimentally verified at select wavelengths from the visible through the near-IR. For comparison, we have also modeled the splitting ratio for several materials which are commonly used as waveguiding devices.

Nanowatt threshold, alumina sensitized neodymium laser integrated on silicon.

Low threshold lasers based on rare-earth elements have enabled numerous scientific discoveries and innovations in industry. However, pushing the threshold into the sub-microwatt regime has been stymied by a fundamental material phenomenon. Specifically, rare earth dopants form clusters which quench emission and reduce efficiency. Here, we fabricate resonant cavity lasers from neodymium-doped silica films containing alumina. The alumina prevents the clustering of the Neodymium, enabling the lasers to achieve thresholds of 530 nanoWatts at room temperature.