NAGase sensing in 3% milk: FET-based specific and label-free sensing in ultra-small samples of high ionic strength and high concentration of non-specific proteins.

Biosensing with biological field-effect transistors (bioFETs) is a promising technology toward specific, label-free, and multiplexed sensing in ultra-small samples. The current study employs the field-effect meta-nano-channel biosensor (MNC biosensor) for the detection of the enzyme N-acetyl-beta-D-glucosaminidase (NAGase), a biomarker for milk cow infections. The measurements are performed in a 0.5 µL drops of 3% commercial milk spiked with NAGase concentrations in the range of 30.3 aM-3.03 µM (Note that there is no background NAGase concentration in commercial milk). Specific and label-free sensing of NAGase is demonstrated with a limit-of-detection of 30.3 aM, a dynamic range of 11 orders of magnitude and with excellent linearity and sensitivity. Additional two important research outcomes are reported. First, the ionic strength of the examined milk is ∼120 mM which implies a bulk Debye screening length <1 nm. Conventionally, a 1 nm Debye length excludes the possibility of sensing with a recognition layer composed of surface bound anti-NAGase antibodies with a size of ∼10 nm. This apparent contradiction is removed considering the ample literature reporting antibody adsorption in a predominantly surface tilted configuration (side-on, flat-on, etc.). Secondly, milk contains a non-specific background protein concentration of 33 mg/ml, in addition to considerable amounts of micron-size heterogeneous fat structures. The reported sensing was performed without the customarily exercised surface blocking and without washing of the non-specific signal. This suggests that the role of non-specific adsorption to the BioFET sensing signal needs to be further evaluated. Control measurements are reported.

From sensing interactions to controlling the interactions: a novel approach to obtain biological transistors for specific and label-free immunosensing.

Antibody-antigen interactions are shaped by the solution pH level, ionic strength, and electric fields, if present. In biological field-effect transistors (BioFETs), the interactions take place at the sensing area in which the pH level, ionic strength and electric fields are determined by the Poisson-Boltzmann equation and the boundary conditions at the solid-solution interface and the potential applied at the solution electrode. The present study demonstrates how a BioFET solution electrode potential affects the sensing area double layer pH level, ionic strength, and electric fields and in this way shapes the biological interactions at the sensing area. We refer to this as 'active sensing'. To this end, we employed the meta-nano-channel (MNC) BioFET and demonstrate how the solution electrode can determine the antibody-antigen equilibrium constant and allows the control and tuning of the sensing performance in terms of the dynamic range and limit-of-detection. In the current work, we employed this method to demonstrate the specific and label-free sensing of Alpha-Fetoprotein (AFP) molecules from 0.5 µL drops of 1 : 100 diluted serum. AFP was measured during pregnancy as part of the prenatal screening program for fetal anomalies, chromosomal abnormalities, and abnormal placentation. We demonstrate AFP sensing with a limit-of-detection of 10.5 aM and a dynamic range of 6 orders of magnitude in concentration. Extensive control measurements are reported.

Arrays of Fresnel Nanosystems for Enhanced Photovoltaic Performance.

Omnidirectional broadband absorption of the solar radiation is pivotal to solar energy harvesting and particularly to low-cost non-tracking photovoltaic (PV) technologies. The current work numerically examines the utilization of surface arrays composed of Fresnel nanosystems (Fresnel arrays), which are reminiscent of the known Fresnel lenses, for the realization of ultra-thin silicon PV cells. Specifically, the optical and electrical performances of PV cells integrated with Fresnel arrays are compared with those of a PV cell incorporated with an optimized surface array of nanopillars (NP array). It is shown that the broadband absorption of specifically tailored Fresnel arrays can provide an enhancement of ∼20% over that of an optimized NP array. The performed analysis suggests that broadband absorption in ultra-thin films decorated with Fresnel arrays is driven by two light trapping mechanisms. The first is light trapping governed by light concentration, induced by the arrays, into the underlying substrates, which increases the optical coupling between the impinging illumination and the substrates. The second mechanism is light trapping motivated by refraction, as the Fresnel arrays induce lateral irradiance in the underlying substrates, which increases the optical interaction length and hence the overall probability for optical absorption. Finally, PV cells incorporated with surface Fresnel arrays are numerically calculated, with short-circuit current densities (Jsc) which are ∼50% higher than that of a PV cell incorporated with an optimized NP array. Also, the effect of increased surface area, due to the presence of Fresnel arrays, and its effect on surface recombination and open-circuit voltage (Voc) are discussed.

Step-Index (Semi-Immersed) Model for Photonic Nanojet and Experimental Characterization via Near-Field Optical Microscopy with Microcylinder.

Experimental limitations such as design complexity and low optical throughput have prevented photonic nanojet (PNJ) and photonic hook (PH) measurements from demonstrating and characterizing the implementation of narrow intense electromagnetic beams generated from dielectric microelements with circular symmetry. Near-fields optical microscopy can mitigate these limitations and still present a capability of detecting a highly localized electromagnetic beam for applications in step-index media. Here we model a localized PNJ and PH formation in step-index media. We show that despite negligible refractive index contrast between the water (nwater=1.33) and silica microcylinder (∼1.1), a formation of PNJ and PH is observed with equivalent performance compared to that of silica microcylinder embedded in air (nair=1). This model features a practical fiber source and silica microcylinder as an auxiliary structure. Simultaneously, we performed experimental characterization of a photonic nanojet generated from an optical fiber and studied the resulting near-fields. Our electromagnetic simulation results are in good agreement with the experimental ones, demonstrating a full width at half maximum (FHWM) with a relative error of 0.64%. This system will make fiber-based nanojet realization and characterization accessible and practical for optics and laser engineering applications, super-resolution imaging, and nanolithography.

A new approach towards the Debye length challenge for specific and label-free biological sensing based on field-effect transistors.

Biologically-modified field-effect transistors (BioFETs) are promising platforms for specific and label-free biosensing due to their sub-micron footprint suitable for multiplexing in ultra-small samples, low noise levels, inherent amplification, etc. Debye screening length is a well-recognized challenge for any BioFET-based technology. The screening length is the smallest at the double layer, where the solution ion population is higher than the bulk population. One way to address the small double layer screening length is to electrostatically modify the potential drop across the solution such as to minimize the potential drop over the double layer. This will decrease the population of the double layer ions and increase the screening length. However, this is not possible with BioFETs as voltage application to the reference electrode simultaneously affects both the double layer and the BioFET conducting channel. The current study addresses the screening length challenge with the novel Meta-Nano-Channel (MNC) BioFET. The MNC BioFET, which is fabricated in a complementary-metal-oxide-silicon (CMOS) process, allows decoupling of the electrostatics of the double layer from the electrodynamics of the conducting channel. The study explores the mechanism of sensing with the MNC BioFET, and demonstrates how the double layer can be electrostatically tuned in order to optimize the screening length without affecting the conducting channel. Finally, specific and label-free sensing of 10 ng ml-1 prostate specific antigen (PSA) is demonstrated. It is shown that by electrostatically increasing the double layer screening length, the sensing signal increases from 70 mV to 133 mV.

Efficiency-Enhanced Scalable Organic Photovoltaics Using Roll-to-Roll Nanoimprint Lithography.

Invited for this month's cover is the group of Prof. Morten Madsen, University of Southern Denmark, together with Stensborg A/S and Dr. Shalev's group at the Ben-Gurion University of the Negev. The image shows the integration of Roll-to-Roll (R2R) light-management foils to enhance efficiency of R2R organic photovoltaics. The Full Paper itself is available at 10.1002/cssc.202101611.

Efficiency-Enhanced Scalable Organic Photovoltaics Using Roll-to-Roll Nanoimprint Lithography.

Light-trapping nanostructures have for decades been researched as a route to enhance the performance of organic solar cells (OSCs). Whereas the power conversion efficiencies (PCEs) of OSCs have reached above 18 %, industrially compatible devices made by scalable processing in air, using only nontoxic solvents and materials, have shown significantly lower performance values. Although light-trapping nanostructures may improve this, the methods for integrating the nanostructures are typically not compatible with industrial scale up. In this work, scalable, industrially compatible, nonfullerene-based OSCs are developed with integrated light-trapping nanostructures at the back electrodes in the devices. The OSCs are made by using scalable roll-to-roll (R2R) and sheet-to-sheet (S2S) processes and the nanostructures are made by using roll-to-plate (R2P) nanoimprint lithography. A fully scalable solution is thereby developed for industrially compatible nanostructured OSCs. The nanostructured devices show enhancements in PCE up to 25 % compared to reference cells, owing to an enhancement in the short-circuit current density (15 %) by enhanced absorption, and improved charge carrier extraction leading to an enhancement in the fill factor (7 %). Optical modeling is utilized to verify the optical effect of the nanostructures. The best devices attain a PCE of 6.5 %, which is the highest reported efficiency for air-processed slot-die coated ITO-free flexible PBDB-T : ITIC devices, here using nontoxic solvents.

Semiconductivity Transition in Silicon Nanowires by Hole Transport Layer.

The surface of nanowires is a source of interest mainly for electrical prospects. Thus, different surface chemical treatments were carried out to develop recipes to control the surface effect. In this work, we succeed in shifting and tuning the semiconductivity of a Si nanowire-based device from n- to p-type. This was accomplished by generating a hole transport layer at the surface by using an electrochemical reaction-based nonequilibrium position to enhance the impact of the surface charge transfer. This was completed by applying different annealing pulses at low temperature (below 400 °C) to reserve the hydrogen bonds at the surface. After each annealing pulse, the surface was characterized by XPS, Kelvin probe measurements, and conductivity measured by FET based on a single Si NW. The mechanism and conclusion were supported experimentally and theoretically. To this end, this strategy has been demonstrated as an essential tool which could pave a new road for regulating semiconductivity and for other low-dimensional nanomaterials.

Broadband solar absorption with silicon metamaterials driven by strong proximity effects.

Absorption of the solar radiation over a wide spectral range is of utmost importance to applications related to the harvesting of solar energy. We numerically demonstrate broadband solar absorption enhancement employing a metamaterial in the form of arrays composed of subwavelength silicon truncated inverted cones, henceforth referred to as light funnel (LF) arrays. We show that the broadband absorption efficiency of an unoptimized LF array is 36% greater compared with an optically-maximized NP array. We show that photon trapping in LF arrays is motivated by proximity effects related to the optical overlap between LFs. We make the distinction between two types of optical overlap: weak overlap in which the coupling between the sparse array modes and the impinging illumination increases with array densification, and strong overlap where the array densification introduces new highly absorbing modes. We show that in nanopillar (NP) arrays the optical intensity inside the NPs decreases upon densification and the overall increase in absorptivity is due to increase in filling ratio (as was also shown by others), while the densification of LF arrays increases the optical intensity inside the individual LF and with the concurrent increase in filling ratio concludes light trapping much superior to that of NP arrays. Light trapping governed by strong proximity effects was not reported to date, and we believe it is an important paradigm for miniaturized lab-on-chip technologies.

Electrostatically Governed Debye Screening Length at the Solution-Solid Interface for Biosensing Applications.

Biosensors based on field-effect devices (bioFETs) offer numerous advantages over current technologies and therefore have attracted immense research over the decades. However, short Debye screening length in highly ionic physiological solutions remains the main obstacle for bioFET realization. This challenge becomes considerably more acute at the electrolyte-oxide interface of the sensing area due to high ion concentration induced by the charged amphoteric sites, which prohibits any attempt to employ the field-effect mechanism to "sense" any charged biomolecules. In this work, we present an electrostatic approach by which the double layer (DL) excess ion concentration is removed, thus forcing the DL ion concentration to match the bulk concentration, which subsequently forces bulk screening length at the DL, thereby "exposing" target biomolecules to the underlying bioFET. To this end, we employ local tunable surface electric fields, introduced to the DL using surface passivated-metal electrodes. We examine numerically and analytically the effect of these electric fields on the DL ion distribution. We also numerically demonstrate the feasibility of the proposed approach for a fully depleted silicon-on-insulator based bioFET and show how the threshold voltage shift induced by the presence of target molecules increases by almost two orders of magnitude upon the removal of the surface excess ion population.

Specific and label-free immunosensing of protein-protein interactions with silicon-based immunoFETs.

The importance of specific and label-free detection of proteins via antigen-antibody interactions for the development of point-of-care testing devices has greatly influenced the search for a more accessible, sensitive, low cost and robust sensors. The vision of silicon field-effect transistor (FET)-based sensors has been an attractive venue for addressing the challenge as it potentially offers a natural path to incorporate sensors with the existing mature Complementary Metal Oxide Semiconductor (CMOS) industry; this provides a stable and reliable technology, low cost for potential disposable devices, the potential for extreme minituarization, low electronic noise levels, etc. In the current review we focus on silicon-based immunological FET (ImmunoFET) for specific and label-free sensing of proteins through antigen-antibody interactions that can potentially be incorporated into the CMOS industry; hence, immunoFETs based on nano devices (nanowire, nanobelts, carbon nanotube, etc.) are not treated here. The first part of the review provides an overview of immunoFET principles of operation and challenges involved with the realization of such devices (i.e. e.g. Debye length, surface functionalization, noise, etc.). In the second part we provide an overview of the state-of-the-art silicon-based immunoFET structures and novelty, principles of operation and sensing performance reported to date.

Approaching the Yablonovitch limit with free-floating arrays of subwavelength trumpet non-imaging light concentrators driven by extraordinary low transmission.

Metamaterials based on arrays of subwavelength dielectric structures have recently proved to be a viable research tool towards the realization of various photonic devices. In the current study we introduce a new approach towards efficient light trapping and broadband absorption of solar radiation based on silicon surface arrays composed of subwavelength trumpet non-imaging light concentrators (henceforth, trumpet arrays). In geometrical optics, a three-dimensional trumpet non-imaging light concentrator is a hyperboloid of revolution with an ideal light concentration ratio. We use finite-difference time-domain electromagnetic calculations to examine the optical response of an infinite cubic-tiled substrate-less silicon trumpet array under normal illumination. The absorptivity spectra of trumpet arrays are characterized by strong absorption peaks, some of which are just below the Yablonovitch limit. The enhanced light trapping is attributed solely to the efficient occupation of the array Mie modes, and we show absorption enhancement at near infrared that is an order of magnitude higher than that of the optimized nanopillar (NP) arrays. We show superior broadband absorption of solar radiation in trumpet arrays (with unoptimized geometry) compared with that of the optimized NP arrays (∼26% enhancement). The higher optical absorption in the trumpet array is governed by low transmissivity, in contrast to the NP array in which the absorption is governed by low reflectivity. Finally, we show that low reflectivity in trumpet arrays is governed by modal excitation at the upper part of the trumpets (which is also supported by the weak dependency of the reflectivity on the array height), whereas the transmissivity is governed by modal excitation at the lower part of the trumpets.

Efficient light trapping and broadband absorption of the solar spectrum in nanopillar arrays decorated with deep-subwavelength sidewall features.

Silicon nanopillar (NP) arrays are known to exhibit efficient light trapping and broadband absorption of solar radiation. In this study, we consider the effect of deep subwavelength sidewall scalloping (DSSS) on the broadband absorption of the arrays. Practically, the formation of DSSS is a side effect of top-down dry etching of NP arrays of several microns height. We use finite-difference time-domain electromagnetic calculations to show that the presence of DSSS can result in efficient excitation of optical modes in both the arrays and the underlying substrates. We demonstrate a broadband absorption enhancement of >10% in a DSSS-NP array with an underlying substrate. Finally, we use device calculations to examine the effect of DSSS on the electrical performance of a photovoltaic cell, as the main concern is the degradation of the open-circuit voltage due to surface recombination (DSSS results in higher surface-to-volume ratio). We show that the effect of DSSS on open-circuit voltage is negligible. Finally, deep-subwavelength sidewall features offer a new, interesting photon management strategy towards absorption enhancement.

Light Trapping with Silicon Light Funnel Arrays.

Silicon light funnels are three-dimensional subwavelength structures in the shape of inverted cones with respect to the incoming illumination. Light funnel (LF) arrays can serve as efficient absorbing layers on account of their light trapping capabilities, which are associated with the presence of high-density complex Mie modes. Specifically, light funnel arrays exhibit broadband absorption enhancement of the solar spectrum. In the current study, we numerically explore the optical coupling between surface light funnel arrays and the underlying substrates. We show that the absorption in the LF array-substrate complex is higher than the absorption in LF arrays of the same height (~10% increase). This, we suggest, implies that a LF array serves as an efficient surface element that imparts additional momentum components to the impinging illumination, and hence optically excites the substrate by near-field light concentration, excitation of traveling guided modes in the substrate, and mode hybridization.

Control of the Intrinsic Sensor Response to Volatile Organic Compounds with Fringing Electric Fields.

The ability to control surface-analyte interaction allows tailoring chemical sensor sensitivity to specific target molecules. By adjusting the bias of the shallow p-n junctions in the electrostatically formed nanowire (EFN) chemical sensor, a multiple gate transistor with an exposed top dielectric layer allows tuning of the fringing electric field strength (from 0.5 × 107 to 2.5 × 107 V/m) above the EFN surface. Herein, we report that the magnitude and distribution of this fringing electric field correlate with the intrinsic sensor response to volatile organic compounds. The local variations of the surface electric field influence the analyte-surface interaction affecting the work function of the sensor surface, assessed by Kelvin probe force microscopy on the nanometer scale. We show that the sensitivity to fixed vapor analyte concentrations can be nullified and even reversed by varying the fringing field strength, and demonstrate selectivity between ethanol and n-butylamine at room temperature using a single transistor without any extrinsic chemical modification of the exposed SiO2 surface. The results imply an electric-field-controlled analyte reaction with a dielectric surface extremely compelling for sensitivity and selectivity enhancement in chemical sensors.

Addressing carrier extraction from optically-optimized nanopillar arrays for thin-film photovoltaics.

Decorating the top surface of silicon solar cells with nanopillar arrays of subwavelength periodicity is a promising path toward low-cost thin-film photovoltaics with enhanced solar radiation absorption due to the inherent light trapping capabilities of nanopillar arrays. Common practice and knowledge for the efficient carrier extraction from the excited nanopillars is the formation of ultra-shallow radial p-n junctions that provide both short carrier collection lengths, and also ensure that the volume of the photo inactive emitter is as small as possible. In the current manuscript, both finite-difference time-domain simulations and three-dimensional device simulations are used to examine carrier extraction from nanopillar arrays that are geometrically optimized in terms of array periodicity and nanopillar diameter to provide maximum absorption of the solar spectrum. The discussion is limited to nanopillars with heights of 2 µm in line with what is currently available with leading top-down fabrication technologies for the formation of nanopillars with smooth sidewalls and radial uniformity. The examination considers both radial and axial homojunctions for various junction depths. It is shown that, contrary to common practice and knowledge, the ultra-shallow junctions are detrimental to the photovoltaic performance of such systems while the radial configuration with a junction depth of ∼50 nm is the most efficient. Furthermore, the open circuit voltage is highest for axial junctions with a junction depth of 100 nm. Also, it is shown that the axial junction is preferable in the low dopant concentration regime and that overall, the axial junction is less sensitive to variations in junction depth.

The Electrostatically Formed Nanowire: A Novel Platform for Gas-Sensing Applications.

The electrostatically formed nanowire (EFN) gas sensor is based on a multiple-gate field-effect transistor with a conducting nanowire, which is not defined physically; rather, the nanowire is defined electrostatically post-fabrication, by using appropriate biasing of the different surrounding gates. The EFN is fabricated by using standard silicon processing technologies with relaxed design rules and, thereby, supports the realization of a low-cost and robust gas sensor, suitable for mass production. Although the smallest lithographic definition is higher than half a micrometer, appropriate tuning of the biasing of the gates concludes a conducting channel with a tunable diameter, which can transform the conducting channel into a nanowire with a diameter smaller than 20 nm. The tunable size and shape of the nanowire elicits tunable sensing parameters, such as sensitivity, limit of detection, and dynamic range, such that a single EFN gas sensor can perform with high sensitivity and a broad dynamic range by merely changing the biasing configuration. The current work reviews the design of the EFN gas sensor, its fabrication considerations and process flow, means of electrical characterization, and preliminary sensing performance at room temperature, underlying the unique and advantageous tunable capability of the device.

Electrostatic Limit of Detection of Nanowire-Based Sensors.

Scanning gate microscopy is used to determine the electrostatic limit of detection (LOD) of a nanowire (NW) based chemical sensor with a precision of sub-elementary charge. The presented method is validated with an electrostatically formed NW whose active area and shape are tunable by biasing a multiple gate field-effect transistor (FET). By using the tip of an atomic force microscope (AFM) as a local top gate, the field effect of adsorbed molecules is emulated. The tip induced charge is quantified with an analytical electrostatic model and it is shown that the NW sensor is sensitive to about an elementary charge and that the measurements with the AFM tip are in agreement with sensing of ethanol vapor. This method is applicable to any FET-based chemical and biological sensor, provides a means to predict the absolute sensor performance limit, and suggests a standardized way to compare LODs and sensitivities of various sensors.

Enhanced photovoltaics inspired by the fovea centralis.

The fovea centralis is a closely-packed vertical array of inverted-cone photoreceptor cells located in the retina that is responsible for high acuity binocular vision. The cones are operational in well-lit environments and are responsible for trapping the impinging illumination. We present the vertical light-funnel silicon array as a light-trapping technique for photovoltaic applications that is bio-inspired by the properties of the fovea centralis. We use opto-electronic simulations to evaluate the performance of light-funnel solar cell arrays. Light-funnel arrays present ~65% absorption enhancement compared to a silicon film of identical thickness and exhibit power conversion efficiencies that are 60% higher than those of optimized nanowire arrays of the same thickness although nanowire arrays consist of more than 2.3 times the amount of silicon. We demonstrate the superior absorption of the light-funnel arrays as compared with recent advancements in the field. Fabrication of silicon light-funnel arrays using low-cost processing techniques is demonstrated.

Peptides mimicking the unique ARTS-XIAP binding site promote apoptotic cell death in cultured cancer cells.

PURPOSE: XIAP [X-linked inhibitor of apoptosis (IAP) protein] is the best characterized mammalian caspase inhibitor. XIAP is frequently overexpressed in a variety of human tumors, and genetic inactivation of XIAP in mice protects against lymphoma. Therefore, XIAP is an attractive target for anticancer therapy. IAP antagonists based on a conserved IAP-binding motif (IBM), often referred to as "Smac-mimetics," are currently being evaluated for cancer therapy in the clinic. ARTS (Sept4_i2) is a mitochondrial proapoptotic protein which promotes apoptosis by directly binding and inhibiting XIAP via a mechanism that is distinct from all other known IAP antagonists. Here, we investigated the ability of peptides derived from ARTS to antagonize XIAP and promote apoptosis in cancer cell lines. EXPERIMENTAL DESIGN: The ability of synthetic peptides, derived from the C-terminus of ARTS, to bind to XIAP, stimulate XIAP degradation, and induce apoptosis was examined. We compared the response of several cancer cell lines to different ARTS-derived peptides. Pull-down assays were used to examine binding to XIAP, and apoptosis was evaluated using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, caspase activation, and Western blot analyses of caspase substrates. RESULTS: The C-terminus of ARTS contains a unique sequence, termed ARTS-IBM (AIBM), which is important for binding to XIAP and cell killing. AIBM peptides can bind to XIAP-BIR3, penetrate cancer cells, reduce XIAP levels, and promote apoptosis. CONCLUSIONS: Short synthetic peptides derived from the C-terminus of ARTS are sufficient for binding to XIAP and can induce apoptosis in cancer cells. These results provide proof-of-concept for the feasibility of developing ARTS-based anticancer therapeutics.