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Rapid identification of microparticles in liquid is an important problem in environmental and biomedical applications such as for microplastic detection in water sources and physiological fluids. Existing spectro-scopic techniques are usually slow and not compatible with flow-through systems. Here we analyze single microparticles in the 14 - 20 micrometer range using a combination of two electronic sensors in the same microfluidic system: a microwave capacitive sensor and a resistive pulse sensor. Together, this integrated sen-sor system yields the effective electrical permittivity of the analyte particles. To simplify data analysis, 3D electrode arrangements were used instead of planar electrodes, so that the generated signal is unaffected by the height of the particle in the microfluidic channel. With this platform, we were able to distinguish between polystyrene (PS) and polyethylene (PE) microparticles. We showcase the sensitivity and speed of this tech-nique and discuss the implications for the future application of microwave cytometry technology in the en-vironmental and biomedical fields., Comment: 7 pages, 4 figures

Reservoir computing offers an energy-efficient alternative to deep neural networks (DNNs) by replacing complex hidden layers with a fixed nonlinear system and training only the final layer. This work investigates nanoelectromechanical system (NEMS) resonators for reservoir computing, utilizing inherent nonlinearities and the fading memory effect from NEMS's transient response. This approach transforms input data into a higher-dimensional space for effective classification. The smaller size and higher operating frequencies of the NEMS resonators enable faster processing rates than recent demonstrations with micromechanical systems, while their compact footprint and ability to operate under ambient conditions simplify integration into practical applications. Through an MNIST handwritten digit recognition test, this system achieved 90% accuracy with a 3.3-microsecond processing time per pixel, highlighting the potential for various applications that require efficient and fast information processing in resource-constrained environments., Comment: 21 pages. 4 figures

Weight enumerators are important tools for deciphering the algebraic structure of the related code spaces and for understanding group actions on these spaces. Our study focuses on symmetrized weight enumerators of pairs of Type II codes over the finite field $\mathbb{F}_{2}$ and the ring $\mathbb{Z}_{4}$. These pairs have been examined as invariants for a specified group. In particular, we concentrate on the scenarios where the space of the invariant ring is of degree 8 and 16. Our findings show that in certain situations, the ring produced by the symmetrized weight enumerators precisely matches with the invariant ring of the designated group. This coincidence points to a profound relationship between the invariant ring's structure and the algebraic characteristics of the weight enumerators., Comment: 9 Pages including Appendix

Microwave sensors integrated with microfluidic platforms can provide the size and permittivity of single cells and microparticles. Amongst the microwave sensor topologies, the planar arrangement of electrodes is a popular choice owing to the ease of fabrication. Unfortunately, planar electrodes generate a non-uniform electric field which causes the responsivity of the sensor to depend on the vertical position of a microparticle in the microfluidic channel. To overcome this problem, we fabricated three-dimensional (3D) electrodes at the coplanar sensing region of an underlying microwave resonator. The 3D electrodes are based on SU8 polymer which is then metallized by sputter coating. With this system, we readily characterized a mixture composed of 12 um and 20 um polystyrene particles and demonstrated separation without any position-related calibration. The ratio of the electronic response of the two particle types is approximately equal to the ratio of the particle volumes, which indicates the generation of a uniform electric field at the sensing region. The current work obviates the need for using multiple coplanar electrodes and extensive processing of the data for the calibration of particle height in a microfluidic channel: as such, it enables the fabrication of more sophisticated microwave resonators for environmental and biological applications.

The characterization of individual nanoparticles in a liquid constitutes a critical challenge for environmental, material, and biological sciences. To detect nanoparticles, electronic approaches are especially desirable owing to their compactness and lower costs. Indeed, for single-molecule and single-nanoparticle detection, resistive pulse sensing has advanced significantly during the last two decades. While resistive pulse sensing was widely used to obtain the geometric size information, impedimetric measurements to obtain dielectric signatures of nanoparticles have scarcely been reported. To explore this orthogonal sensing modality, we developed an impedimetric sensor based on a microwave resonator with a nanoscale sensing gap surrounding a nanopore. The approach of single nanoparticles near the sensing region and their translocation through the nanopore induced sudden changes in the impedance of the structure. The impedance changes in turn were picked up by the phase response of the microwave resonator. We worked with 100 nm and 50 nm polystyrene nanoparticles to observe single-particle events. Our current implementation was limited by the non-uniform electric field at the sensing region. The work provides a complementary sensing modality for nanoparticle characterization where the dielectric response, rather than the ionic current, determines the signal., Comment: 22 pages, 6 figures

The scanning electron microscope (SEM) recordings of dynamic nano-electromechanical systems (NEMS) are difficult to analyze due to the noise caused by low frame rate, insufficient resolution and blurriness induced by applied electric potentials. Here, we develop an image processing algorithm enhanced by the physics of the underlying system to track the motion of buckling NEMS structures in the presence of high noise levels. The algorithm is composed of an image filter, two data filters, and a nonlinear regression model, which utilizes the expected form of the physical solution. The method was applied to the recordings of a NEMS beam about 150 nm wide, undergoing intra-and inter-well post-buckling states with a transition rate of approximately 0.5 Hz. The algorithm can track the dynamical motion of the NEMS and capture the dependency of deflection amplitude on the compressive force on the beam. With the help of the proposed algorithm, the transition from inter-well to intra-well motion is clearly resolved for buckling NEMS imaged under SEM., Comment: 7 pages, 7 figures. 1 Supplementary Video

Weighing particles above MegaDalton mass range has been a persistent challenge in commercial mass spectrometry. Recently, nanoelectromechanical systems-based mass spectrometry (NEMS-MS) has shown remarkable performance in this mass range, especially with the advance of performing mass spectrometry under entirely atmospheric conditions. This advance reduces the overall complexity and cost, while improving the limit of detection. However, this technique required the tracking of two mechanical modes, and the accurate knowledge of mode shapes which may deviate from their ideal values especially due to air damping. Here, we used a NEMS architecture with a central platform, which enables the calculation of mass by single mode measurements. Experiments were conducted using polystyrene and gold nanoparticles to demonstrate the successful acquisition of mass spectra using a single mode, with improved areal capture efficiency. This advance represents a step forward in NEMS-MS, bringing it closer to becoming a practical application for mass sensing of nanoparticles., Comment: 24 pages, 4 figures

Optical coherence tomography (OCT) is a label-free, non-invasive 3D imaging tool widely used in both biological research and clinical diagnosis. Current OCT modalities can only visualize specimen tomography without chemical information. Here, we report a bondselective full-field OCT (BS-FF-OCT), in which a pulsed mid-infrared laser is used to modulate the OCT signal through the photothermal effect, achieving label-free bond-selective 3D sectioned imaging of highly scattering samples. We first demonstrate BS-FF-OCT imaging of 1 {\mu}m PMMA beads embedded in agarose gel. Next, we then show 3D hyperspectral imaging of polypropylene fiber mattress from a standard surgical mask. We then demonstrate BS-FFOCT imaging on biological samples, including cancer cell spheroids and C. elegans. Using an alternative pulse timing configuration, we finally demonstrate the capability of BS-FF-OCT on a bulky and highly scattering 150 {\mu}m thick mouse brain slice.

Clinical identification and fundamental study of viruses rely on the detection of viral proteins or viral nucleic acids. Yet, amplification-based and antigen-based methods are not able to provide precise compositional information of individual virions due to small particle size and low-abundance chemical contents (e.g., ~ 5000 proteins in a vesicular stomatitis virus). Here, we report a widefield interferometric defocus-enhanced mid-infrared photothermal (WIDE-MIP) microscope for high-throughput fingerprinting of single viruses. With the identification of feature absorption peaks, WIDE-MIP reveals the contents of viral proteins and nucleic acids in single DNA vaccinia viruses and RNA vesicular stomatitis viruses. Different nucleic acids signatures of thymine and uracil residue vibrations are obtained to differentiate DNA and RNA viruses. WIDE-MIP imaging further reveals an enriched \b{eta} sheet components in DNA varicella-zoster virus proteins. Together, these advances open a new avenue for compositional analysis of viral vectors and elucidating protein function in an assembled virion.

Illumination uniformity is a critical parameter for excitation and data extraction quality in widefield biological imaging applications. However, typical imaging systems suffer from spatial and spectral non-uniformity due to non-ideal optical elements, thus require complex solutions for illumination corrections. We present Effective Uniform Color-Light Integration Device (EUCLID), a simple and cost-effective illumination source for uniformity corrections. EUCLID employs a diffuse-reflective, adjustable hollow cavity that allows for uniform mixing of light from discrete light sources and modifies the source field distribution to compensate for spatial non-uniformity introduced by optical components in the imaging system. In this study, we characterize the light coupling efficiency of the proposed design and compare the uniformity performance with the conventional method. EUCLID demonstrates a remarkable illumination improvement for multi-spectral imaging in both Nelsonian and Koehler alignment with a maximum spatial deviation of ~1% across a wide field-of-view.

Interferometric scattering microscopy has been a very promising technology for highly sensitive label-free imaging of a broad spectrum of biological nanoparticles from proteins to viruses in a high-throughput manner. Although it can reveal the specimen's size and shape information, the chemical composition is inaccessible in interferometric measurements. Infrared spectroscopic imaging provides chemical specificity based on inherent chemical bond vibrations of specimens but lacks the ability to image and resolve individual nanoparticles due to long infrared wavelengths. Here, we describe a bond-selective interferometric scattering microscope where the mid-infrared induced photothermal signal is detected by a visible beam in a wide-field common-path interferometry configuration. A thin film layered substrate is utilized to reduce the reflected light and provide a reference field for the interferometric detection of the weakly scattered field. A pulsed mid-IR laser is employed to modulate the interferometric signal. Subsequent demodulation via a virtual lock-in camera offers simultaneous chemical information about tens of micro- or nano-particles. The chemical contrast arises from a minute change in the particle's scattered field in consequence of the vibrational absorption at the target molecule. We characterize the system with sub-wavelength polymer beads and highlight biological applications by chemically imaging several microorganisms including Staphylococcus aureus, Escherichia coli, and Candida albicans. A theoretical framework is established to extend bond-selective interferometric scattering microscopy to a broad range of biological micro- and nano-particles.

Mid-infrared photothermal (MIP) microscopy has been a promising label-free chemical imaging technique for functional characterization of specimens owing to its enhanced spatial resolution and high specificity. Recently developed wide-field MIP imaging modalities have drastically improved speed and enabled high-throughput imaging of micron-scale subjects. However, the weakly scattered signal from sub-wavelength particles becomes indistinguishable from the shot-noise as a consequence of the strong background light, leading to limited sensitivity. Here, we demonstrate background-suppressed chemical fingerprinting at a single nanoparticle level by selectively attenuating the reflected light through pupil engineering in the collection path. Our technique provides over three orders of magnitude background suppression by quasi-darkfield illumination in epi-configuration without sacrificing lateral resolution. We demonstrate 6-fold signal-to-background noise ratio improvement, allowing for simultaneous detection and discrimination of hundreds of nanoparticles across a field of view of 70 um x 70 um. A comprehensive theoretical framework for photothermal image formation is provided and experimentally validated with 300 and 500~nm PMMA beads. The versatility and utility of our technique are demonstrated via hyperspectral dark-field MIP imaging of S. aureus and E. coli bacteria., Comment: 33 pages, 7 figures, journal article

Mass spectrometry of intact nanoparticles and viruses can serve as a potent characterization tool for material science and biophysics. Inaccessible by widespread commercial techniques, the mass of single nanoparticles and viruses (>10MDa) can be readily measured by NEMS (Nanoelectromechanical Systems) based Mass Spectrometry, where charged and isolated analyte particles are generated by Electrospray Ionization (ESI) in air and transported onto the NEMS resonator for capture and detection. However, the applicability of NEMS as a practical solution is hindered by their miniscule surface area, which results in poor limit-of-detection and low capture efficiency values. Another hindrance is the necessity to house the NEMS inside complex vacuum systems, which is required in part to focus analytes towards the miniscule detection surface of the NEMS. Here, we overcome both limitations by integrating an ion lens onto the NEMS chip. The ion lens is composed of a polymer layer, which charges up by receiving part of the ions incoming from the ESI tip and consequently starts to focus the analytes towards an open window aligned with the active area of the NEMS electrostatically. With this integrated system, we have detected the mass of gold and polystyrene nanoparticles under ambient conditions and with two orders-of-magnitude improvement in capture efficiency compared to the state-of-the-art. We then applied this technology to obtain the mass spectrum of SARS-CoV-2 and BoHV-1 virions. With the increase in analytical throughput, the simplicity of the overall setup and the operation capability under ambient conditions, the technique demonstrates that NEMS Mass Spectrometry can be deployed for mass detection of engineered nanoparticles and biological samples efficiently., Comment: 38 pages, 6 figures

We study the spectral properties of the thermal force giving rise to the Brownian motion of a continuous mechanical system -- namely, a nanomechanical beam resonator -- in a viscous liquid. To this end, we perform two separate sets of experiments. First, we measure the power spectral density (PSD) of the position fluctuations of the resonator around its fundamental mode at its center. Then, we measure the frequency-dependent linear response of the resonator, again at its center, by driving it with a harmonic force that couples well to the fundamental mode. These two measurements allow us to determine the PSD of the Brownian force noise acting on the structure in its fundamental mode. The PSD of the force noise extracted from multiple resonators spanning a broad frequency range displays a "colored spectrum". Using a single-mode theory, we show that, around the fundamental resonances of the resonators, the PSD of the force noise follows the dissipation of a blade oscillating in a viscous liquid -- by virtue of the fluctuation-dissipation theorem., Comment: Main Article 7 Pages, 4 figures, 1 table; supplementary 22 pages, 17 figures, 3 tables; to be published in ACS Nanoletters

Microwave sensors can probe intrinsic material properties of analytes in a microfluidic channel at physiologically relevant ion concentrations. While microwave sensors have been used to detect single cells and microparticles in earlier studies, the synergistic use and comparative analysis of microwave sensors with optical microscopy for material classification and size tracking applications have been scarcely investigated so far. Here we combined microwave and optical sensing to differentiate microscale objects based on their dielectric properties. We designed and fabricated two types of planar sensor: a Coplanar Waveguide Resonator (CPW) and a Split-Ring Resonator (SRR). Both sensors possessed sensing electrodes with a narrow gap to detect single cells passing through a microfluidic channel integrated on the same chip. We also show that standalone microwave sensors can track the relative changes in cellular size in real-time. In sensing single 20-micron diameter polystyrene particles, Signal-to-Noise ratio values of approximately 100 for CPW and 70 for SRR sensors were obtained. These findings demonstrate that microwave sensing technology can serve as a complementary technique for single-cell biophysical experiments and microscale pollutant screening.

Bacterial infectious diseases are a major threat to human health. Timely and sensitive pathogenic bacteria detection is crucial in identifying the bacterial contaminations and preventing the spread of infectious diseases. Due to limitations of conventional bacteria detection techniques there have been concerted research efforts towards development of new biosensors. Biosensors offering label free, whole bacteria detection are highly desirable over those relying on label based or pathogenic molecular components detection. The major advantage is eliminating the additional time and cost required for labeling or extracting the desired bacterial components. Here, we demonstrate rapid, sensitive and label free E. coli detection utilizing interferometric reflectance imaging enhancement allowing for visualizing individual pathogens captured on the surface. Enabled by our ability to count individual bacteria on a large sensor surface, we demonstrate a limit of detection of 2.2 CFU/ml from a buffer solution with no sample preparation. To the best of our knowledge, this high level of sensitivity for whole E. coli detection is unprecedented in label free biosensing. The specificity of our biosensor is validated by comparing the response to target bacteria E. coli and non target bacteria S. aureus, K. pneumonia and P. aeruginosa. The biosensor performance in tap water also proves that its detection capability is unaffected by the sample complexity. Furthermore, our sensor platform provides high optical magnification imaging and thus validation of recorded detection events as the target bacteria based on morphological characterization. Therefore, our sensitive and label free detection method offers new perspectives for direct bacterial detection in real matrices and clinical samples., Comment: 15 pages, 6 figures, 1 table

Nanomechanical resonators are used in building ultra-sensitive mass and force sensors. In a widely used resonator based sensing paradigm, each modal resonance frequency is tracked with a phase-locked loop (PLL) based system. There is great interest in deciphering the fundamental sensitivity limitations due to inherent noise and fluctuations in PLL based resonant sensors to improve their performance. In this paper, we present a precise, first-principles based theory for the analysis of PLL based resonator tracking systems. Based on this theory, we develop a general, rigorously-derived noise analysis framework for PLL based sensors. We apply this framework to a setting where the sensor performance is mainly limited by the thermomechanical noise of the nanomechanical resonator. The results that are deduced through our analysis framework are in complete agreement with the ones we obtain from extensive, carefully run stochastic simulations of a PLL based sensor system. We compare the conclusions we derive with the recent results in the literature. Our theory and analysis framework can be used in assessing PLL based sensor performance with other sources of noise, e.g., from the electronic components, actuation and sensing mechanisms, and due to the signal generator, as well as for a variety of PLL based sensor configurations such as multi-mode and nonlinear sensing., Comment: 37 pages, 8 figures

Buckling at the micro and nanoscale generates distant bistable states which can be beneficial for sensing, shape-reconfiguration and mechanical computation applications. Although different approaches have been developed to access buckling at small scales, such as the use heating or pre-stressing beams, very little attention has been paid so far to dynamically and precisely control all the critical bifurcation parameters, the compressive stress and the lateral force on the beam. Precise and on-demand generation of compressive stress on individually addressable microstructures is especially critical for morphologically reconfigurable devices. Here, we develop an all-electrostatic architecture to control the compressive force, as well as the direction and amount of buckling, without significant heat generation on micro/nano structures. With this architecture, we demonstrated fundamental aspects of device function and dynamics. By applying voltages at any of the digital electronics standards, we have controlled the direction of buckling. Lateral deflections as large as 12% of the beam length were achieved. By modulating the compressive stress and lateral electrostatic force acting on the beam, we tuned the potential energy barrier between the post-bifurcation stable states and characterized snap-through transitions between these states. The proposed architecture opens avenues for further studies that can enable efficient actuators and multiplexed shape-shifting devices.

Nanoelectromechanical Systems (NEMS) have emerged as a promising technology for performing the mass spectrometry of large biomolecules and nanoparticles. As nanoscale objects land on NEMS sensor one by one, they induce resolvable shifts in the resonance frequency of the sensor proportional to their weight. The operational regime of NEMS sensors is often limited by the onset-of-nonlinearity, beyond which the highly sensitive schemes based on frequency tracking by phase-locked loops cannot be readily used. Here, we develop a measurement architecture to operate at the nonlinear regime and measure frequency shifts induced by analytes in a rapid and sensitive manner. We used this architecture to individually characterize the mass of gold nanoparticles and verified the results by performing independent measurements of the same nanoparticles based on linear mass sensing. Once the feasibility of the technique is established, we have obtained the mass spectrum of a 20 nm gold nanoparticle sample by individually recording about five hundred single particle events using two modes working sequentially in the nonlinear regime. The technique obtained here can be used for thin nanomechanical structures which possess a limited dynamic range.

The clinical need for ultra-sensitive molecular analysis has motivated the development of several endpoint assay technologies capable of single molecule readout. These endpoint assays are now primarily limited by the affinity and specificity of the molecular recognition agents for the analyte of interest. In contrast, a kinetic assay with single molecule readout could distinguish between low abundance, high affinity (specific analyte) and high abundance, low affinity (nonspecific background) binding by measuring the duration of individual binding events at equilibrium. Here we describe such a kinetic assay, in which individual binding events are detected and monitored during sample incubation. This method uses plasmonic gold nanorods and interferometric reflectance imaging to detect thousands of individual binding events across a multiplex solid phase sensor with a large area approaching that of leading bead-based endpoint assay technologies. A dynamic tracking procedure is used to measure the duration of each event. From this, the total rates of binding and de-binding as well as the distribution of binding event durations are determined. We observe a limit of detection of 15 femtomolar for a proof-of-concept synthetic DNA analyte in a 12-plex assay format., Comment: 16 pages, 7 figures

Day-ahead scheduling of electricity generation or unit commitment is an important and challenging optimization problem in power systems. Variability in net load arising from the increasing penetration of renewable technologies have motivated study of various classes of stochastic unit commitment models. In two-stage models, the generation schedule for the entire day is fixed while the dispatch is adapted to the uncertainty, whereas in multi-stage models the generation schedule is also allowed to dynamically adapt to the uncertainty realization. Multi-stage models provide more flexibility in the generation schedule, however, they require significantly higher computational effort than two-stage models. To justify this additional computational effort, we provide theoretical and empirical analyses of the value of multi-stage solution for risk-averse multi-stage stochastic unit commitment models. The value of multi-stage solution measures the relative advantage of multi-stage solutions over their two-stage counterparts. Our results indicate that, for unit commitment models, value of multi-stage solution increases with the level of uncertainty and number of periods, and decreases with the degree of risk aversion of the decision maker., Comment: 8 pages, 5 figures

DNA and protein microarrays are a high-throughput technology that allow the simultaneous quantification of tens of thousands of different biomolecular species. The mediocre sensitivity and dynamic range of traditional fluorescence microarrays compared to other techniques have been the technology's Achilles' Heel, and prevented their adoption for many biomedical and clinical diagnostic applications. Previous work to enhance the sensitivity of microarray readout to the single-molecule ('digital') regime have either required signal amplifying chemistry or sacrificed throughput, nixing the platform's primary advantages. Here, we report the development of a digital microarray which extends both the sensitivity and dynamic range of microarrays by about three orders of magnitude. This technique uses functionalized gold nanorods as single-molecule labels and an interferometric scanner which can rapidly enumerate individual nanorods by imaging them with a 10x objective lens. This approach does not require any chemical enhancement such as silver deposition, and scans arrays with a throughput similar to commercial fluorescence devices. By combining single-nanoparticle enumeration and ensemble measurements of spots when the particles are very dense, this system achieves a dynamic range of about one million directly from a single scan.