Tunable Dynamic Range Research Articles

Effects of Salt Concentration on a Magnetic Nanoparticle-Based Aggregation Assay with a Tunable Dynamic Range.

Magnetic nanoparticles (MNPs) can be functionalized with antibodies to give them an affinity for a biomarker of interest. Functionalized MNPs (fMNPs) cluster in the presence of a multivalent target, causing a change in their magnetization. Target concentration can be proportional to the 3rd harmonic phase of the fMNP magnetization signal. fMNP clustering can also be induced with salt. Generally, salt can alter the stability of charge stabilized fMNPs causing a change in magnetization that is not proportional to the target concentration. We have developed a model system consisting of biotinylated MNPs (biotin-MNPs) that target streptavidin to study the effects of salt concentration on fMNP-based biosensing in simulated in vivo conditions. We have found that biotin-MNP streptavidin targeting was independent of salt concentration for 0.005x to 1.00x phosphate buffered saline (PBS) solutions. Additionally, we show that our biosensor's measurable concentration range (dynamic range) can be tuned with biotin density. Our results can be leveraged to design an in vivo nanoparticle (NP)-based biosensor with enhanced efficacy in the event of varying salt concentrations.

Electrostatically actuated all metal MEMS Pirani gauge with tunable dynamic range

An electrostatically actuated all-metal microelectromechanical systems (MEMS) Pirani gauge with a tunable dynamic range is proposed. Contrary to the conventional fixed gap Pirani gauges, an electrostatic mechanism is employed to tune the gaseous conduction gap. Due to the electrostatic force between the heating element and heat sink, this tuning results in shifting the transition pressure to a higher pressure. As a result, the operating range of the Pirani gauge can be tuned depending on the magnitude of the actuation voltage. Theoretical estimation of the transition pressure corresponding to different gaseous conduction gaps is also presented. Depending on the available margin of gap tuning, the electromechanical and electrothermal analyses are carried out in COMSOL Multiphysics. The analytical approach is validated by experimentally characterizing the fabricated device. The experimentally tested device with the proposed actuation mechanism shows an 11.2 dB increase in dynamic range in comparison to the conventional design. In a complementary metal-oxide-semiconductor (CMOS)-compatible fabrication process flow, the proposed gauge can be used to monitor vacuum from 40 Pa to 5 × 105 Pa with the electrostatic actuation.

Engineered DNA bonsai system for ultrasensitive wide-field determination and intracellular dynamic imaging of protein with tunable dynamic range and sensitivity

Herein, an engineered DNA bonsai system was assembled using DNA nanocube (DNC) as pot and a group of DNA recognition hairpins (RHpn, n = 1–5) as plants for ultrasensitive wide-field detection and dynamic intracellular imaging of matrix metalloproteinase-2 (MMP-2) with tunable dynamic range and sensitivity. Impressively, by changing the stem length of the RHpn (n = 1–5), the thermodynamic parameter free energy (△G) of RHpn was regulated to control the binding reaction between RHpn and output target (OT) (like changing the plants species of bonsai, Bonsai 4-RHpn, n = 1–5). When the △G of RHpn was low, the target detection in high concentration range could be achieved. Conversely, the target detection within the low concentration range also could be realized with the high △G of RHpn. Therefore, the developed biosensing platform based on the engineered DNA bonsai system could achieve the ultrasensitive wide-field determination of MMP-2 with 150000-fold tuned detection sensitivity. Meanwhile, by virtue of the spatial restriction effect of DNC to vary the loaded number and the local concentration of RHp1 (like changing the plants density of bonsai, Bonsai n-RHp1, n = 1–4), the kinetic property of the binding process between RHp1 and OT could be manipulated, in which a low substrate concentration leaded to a low reaction efficiency and a high local concentration resulted in a quick reaction rate with high collision probability. Moreover, the designed DNA bonsai system with the highest local concentration (Bonsai 4-RHp1) could achieve rapid detection of the target MMP-2, which easily conquered the main predicaments of dynamic detection methods: limited dynamic range and low detection efficiency. Most importantly, the programmable DNA bonsai system had been successfully applied in ultrasensitive and high-efficient dynamic visualization of protein MMP-2 in living cells, which could not only make it possible to quickly and precisely monitor disease related proteins with tiny changes at different concentration ranges, but also possess tremendous potential to provide high-precision disease information at different stages in disease diagnosis and prognosis monitoring.

Specific and Label‐Free Sensing of Prostate‐Specific Antigen (PSA) from an Ultrasmall Drop of Diluted Human Serum with the Meta‐Nano‐Channel Silicon Field‐Effect Biosensor

AbstractSelf‐use tests are the future of medical diagnostics. Hence, there is a need for low‐cost, simple‐to‐use sensing of multiple analytes from ultrasmall physiological samples. The Meta‐Nano‐Channel (MNC) field‐effect biosensor is employed for sensing of prostate‐specific antigen (PSA). The novelty of the MNC biosensor is: (1) it allows to optimize the coupling between the electrostatics of the biological interactions and the readout current, and (2) it allows to electrostatically affect the biological complexes postinteraction. These attributes yield an optimized and tunable sensing performance. The MNC biosensor is fabricated in a high‐volume silicon chip factory for this research, and an excellent repeatability and robustness in an environment of 1:100 diluted serum is demonstrated. Specific and label‐free PSA sensing is demonstrated from ultrasmall 0.5 µL drops of 1:100 diluted serum with a limit‐of‐detection of 1 fg mL−1, and excellent linearity over a concentration range of six orders of magnitude. Importantly, the attributes of the MNC biosensor allow for a tunable sensitivity and a tunable dynamic range.

Microwave-photonic optical fiber interferometers for wavelength interrogation of fiber Bragg grating sensors with high sensitivity and a tunable dynamic range.

We propose and demonstrate a new, to the best of our knowledge, microwave interference-based scheme with high sensitivity and tunable measurement range, which is realized by a Mach-Zehnder interferometer (MZI). A chirped fiber Bragg grating and single-mode fiber serve as the two unbalanced arms of the RF interferometer. The induced differential chromatic dispersion transfers the wavelength shift of the fiber Bragg gratings to the change of the RF phase difference between the two interferometric carriers, which ultimately leads to the variation of the RF signal intensity. The phase sensitivity can be improved by adjusting the power ratio of the two beams in the interferometer and coarse adjustment of the optical variable delay line (OVDL). The OVDL is also employed to tune the measurement range of the system by adjusting the time delay difference between the two arms of the MZI. The system effectively solves the problem of unavoidable attenuation of the sensitivity of the optical carrier-based microwave interferometry system caused by the change of phase difference due to the change of measurement parameters, avoiding the mutual constraint between the measurement range and high sensitivity.

An enzyme-responsive electrochemical DNA biosensor achieving various dynamic range by using only-one immobilization probe

Developing a simple and easy-to-operate biosensor with tunable dynamic range would provide enormous opportunities to promote the diagnostic applications. Herein, an enzyme-responsive electrochemical DNA biosensor is developed by using only-one immobilization probe. The immobilization probe was designed with a two-loop hairpin-like structure that contained the mutually independent target recognition and enzyme (EcoRI restriction endonuclease) responsive domains. The target recognition was based on a toehold-mediated strand displacement reaction strategy. The toehold region was initially caged in the loop of the immobilization probe and showed a relatively low binding affinity with target, which was improved via EcoRI cleavage of immobilization probe to liberate the toehold region. The EcoRI cleavage operation for immobilization probe demonstrated the well regulation ability in detection performance. It showed a largely extended dynamic range, a significantly lowered detection limit and better discrimination ability toward the mismatched sequences whether in two buffers (with high or low salt concentrations) or in the serum system. The advantages also includes simplicity in probe design, and facile biosensor fabrication and operation. It thus opens a new avenue for the development of the modulated DNA biosensor and hold a great potential for the diagnostic applications and drug monitoring.

Activity-Based Self-Enriched SERS Sensor for Blood Metabolite Monitoring

The monitoring of metabolites in biofluids provides critical clues for disease diagnosis and evaluation. Yet, the quantitative detection of metabolites remains challenging for surface-enhanced Raman spectroscopy (SERS) due to poor reproducibility in preparation and manipulation of SERS nanoprobes. Herein, we develop an activity-based, slippery liquid-infused porous surface SERS (abSLIPSERS) sensor for facile quantification of metabolites with unmodified naked metal nanoparticles (NPs) by integrating biocatalysis-boronate oxidation cascades with SLIPS-driven self-concentration and delivering. Upon mixing the target metabolite with a specific oxidase, a H2O2-sensitive phenylboronate probe, and the naked Au NPs, H2O2 produced from the biocatalytic reaction oxidizes the phenylboronate probe to phenol, resulting in a ratiometric SERS response. Meanwhile, the SLIPS enables the complete enrichment of molecules and NPs within an evaporating liquid droplet, delivering the probes to the SERS-active sites for Raman amplification. Compared with conventional SERS biosensors, abSLIPSERS avoids multistep synthesis and biofunctionalization of nanoprobes, which significantly simplifies the detection workflow and improves the reproducibility. The abSLIPSERS sensor also shows tunable dynamic range beyond 4 orders of magnitude and allows quantifying any other metabolites with specific enzymes. We demonstrate abSLIPSERS sensing of lactate, glucose, and choline in human serum for exploring energy metabolism in lung cancer. This study opens up a new opportunity for future point-of-care testing of circulating metabolites by SERS and will help to facilitate the translation of SERS bioanalysis to clinical settings.

Programming the dynamic range of nanobiosensors with engineering poly-adenine-mediated spherical nucleic acid

Spherical nucleic acid (SNA) conjugates consisting of gold cores functionalized with a densely packed DNA shells are of great significance in the field of medical detection and intracellular imaging. Especially, poly adenine (polyA)-mediated SNAs can improve the controllability and reproducibility of DNA assembly on the nanointerface, showing the tunable hybridization ability. However, due to the physics of single-site binding, the biosensor based on SNA usually exhibits a dynamic range spanning a fixed 81-fold change in target concentration, which limits its application in disease monitoring. To address this problem, we report a tri-block DNA-based approach to assemble SNA for nucleic acid detection based on structure-switching mechanism with programmable dynamic range. The tri-block DNA is a FAM-labeled stem-loop structure, which contains three blocks: polyA block as an anchoring block for tunable surface density, stem block with different GC base pair content for varying the structure stability, and the fixed loop block for target recognition. We find that varying the polyA block, the reaction temperature, and the GC base pair, SNA shows different target binding affinity and detection limit but with normally 81-fold dynamic range. We can extend the dynamic range to 1000-fold by using the combination of two SNAs with different affinity, and narrow the dynamic range to 5-fold by sequestration mechanism. Furthermore, the tunable SNA enables sensitive detection of mRNA in cells. Given its tunable dynamic range, such nanobiosensor based on SNA offers new possibility for various biomedical and clinical applications.

A broadband intermodulation reference generator based on artificial nonlinear dipole

AbstractAccurate passive intermodulation (IM) test calls for precise IM reference for verifying and evaluating the test error from the tester, which makes the IM calibrator source with a wide working band and dynamic range important. This letter reports on a low‐cost and broadband IM generator with a compact area of 5 × 5 cm2. The broadband IM source is designed and demonstrated on the coplanar waveguide structure, where an artificial nonlinear dipole is used to generate IM reference. In special, the dipole is constructed by a diode (HSMS 2822) and two independent copper islands with optimized size. By controlling the bias voltage across the diode, the IM magnitude level can be changed accordingly. The IM tunable dynamic range is over 47.5 dB that covers GSM 800 MHz, GSM 900 MHz, DCS 1800 MHz, and TD‐LTE band. Meanwhile, the obtained IM has an improved IM‐bias flat response.

Force-Coded Strategy for the Simultaneous Detection of Multiple Tumor-Related Proteins.

Multiplexed simultaneous detection of various cancer markers is required for accurate diagnosis and treatment of early cancer. In this work, we present a force-coded strategy for the simultaneous detection of tumor-related proteins with tunable dynamic range via magnetic sensing. The multiplexing capability of this method is achieved by designing DNA devices that can recognize different biomarkers and code them with different binding forces measured by the force-induced remnant magnetization spectroscopy, which is not influenced by the color of the light and the solution. Moreover, the force-coded assay with high sensitivity and adjustable detection range is robust, which could be used for practical biological applications such as magnetic sensing, handheld miniaturized systems, and potential in vivo diagnosis.

DNA-encoded MXene-Pt nanozyme for enhanced colorimetric sensing of mercury ions

MXene-based nanozymes have attracted considerable attention in the field of environmental monitoring and medical diagnostics due to their unique properties. However, the low peroxidase-like activity and limited recognition functions of pristine MXenes hinder their further practical applications. Therefore, developing an efficient surface engineering strategy is urgently needed to promote the high performance of MXene-based nanozymes. Herein, a simple, versatile, and DNA-encoded seed-growth strategy was developed for the synthesis of MXene/DNA/Pt nanocomposites, which exhibit excellent peroxidase-like activity in a sequence-dependent manner. Surprisingly, a significant inhibition in peroxidase-like activity of MXene/DNA/Pt nanocomposites by Hg2+ ions is achieved due to the specific capture of Hg2+ by the nanozyme and in situ reduction of partial Hg2+ to Hg0 on the hybrid interface. Importantly, the proposed nanozyme-based Hg2+ sensor displays prominent analytical performance in both environmental and biological fluids, with high sensitivity, selectivity, and tunable dynamic range. Additionally, integrated with a portable centrifugal microfluidic system, the sensor has the potential to enable fast sample-to-answer Hg2+ detection in a high-throughput and point-of-care format. This work not only provides an effective surface engineering strategy for the design of highly active MXene-based nanozymes but also offers a strategy for developing a multimode sensing system for multiple scenario applications.

Solid-Ionic Memory in a van der Waals Heterostructure.

Defect states dominate the performance of low-dimensional nanoelectronics, which deteriorate the serviceability of devices in most cases. But in recent years, some intriguing functionalities are discovered by defect engineering. In this work, we demonstrate a bifunctional memory device of a MoS2/BiFeO3/SrTiO3 van der Waals heterostructure, which can be programmed and erased by solely one kind of external stimuli (light or electrical-gate pulse) via engineering of oxygen-vacancy-based solid-ionic gating. The device shows multibit electrical memory capability (>22 bits) with a large linearly tunable dynamic range of 7.1 × 106 (137 dB). Furthermore, the device can be programmed by green- and red-light illuminations and then erased by UV light pulses. Besides, the photoresponse under red-light illumination reaches a high photoresponsivity (6.7 × 104 A/W) and photodetectivity (2.12 × 1013 Jones). These results highlighted solid-ionic memory for building up multifunctional electronic and optoelectronic devices.

Wide-field determination of aqueous mercury(II) based on tail-extensible DNA fluorescent probe with tunable dynamic range

Mercury (Hg) is one of the most hazardous pollutants, widely distributed in water, atmosphere, and soil, while the Hg contents from different sources are greatly different. Until now, numerous reported methods are only suitable for a kind of sample because they cannot reconcile sensitivity and linear range. In this work, a tail-extensible DNA fluorescent probe for “turn on” detection of Hg2+ with tunable dynamic range and high sensitivity was developed, which was based on segmental hybridization between silver nanoclusters (AgNCs)-covered DNA and different guanine-rich DNAs. By adding adenine-guanine-cytosine (AGC) base repeats as a tail of the guanine-rich DNA, the formation constant of T-Hg2+-T complex was effectively modulated within two orders of magnitude. Based on it, a tunable dynamic range from 0.035 to 0.2 pM to 8.0–120.0 pM was achieved by combining four fluorescent probes with different tail lengths. The Hg2+contents from different sources were successfully measured. This evidenced the proposed sensor’s application toward wide-field detection, which is useful for the direct and objective comparison of results from different sources, and therefore providing a way for solving the shortcomings of reported methods for Hg2+ detection. Additionally,this present method is simple, cost-effective and time-saving, ultrasensitive and highly selective, which is favorable for expanding its applications and subsequent mercury pollution control.

Microwave-photonic optical fiber interferometers for refractive index sensing with high sensitivity and a tunable dynamic range.

We propose and demonstrate an extremely simple yet novel sensing strategy for measurements of a refractive index (RI) based on microwave-photonic optical fiber interferometry. A hybrid interferometric system based on an incoherent optical interferometer (i.e., a Michelson interferometer [MI]) and a coherent optical interferometer (i.e., a Fabry-Perot interferometer [FPI]) is constructed simply by using a low-cost off-the-shelf fiber coupler. The sensing arm of the MI is highly sensitive to a surrounding RI based on Fresnel reflection, where variations of the ambient RI cause changes in both the reflection magnitudes of the resonance frequencies and fringe visibility of the reflection spectra in the microwave domain. The coherent FPI is employed to tune the dynamic range of the MI by adjusting the effective reflectance of the reference arm of the MI. Essentially, other approaches that can vary the reflectance of the reference arm of the MI can also be used to tune the dynamic range of the system based on the proposed strategy. The experimental results are in good agreement with theoretical predictions. The prominent advantages of the sensor, including low cost, ease of fabrication, robustness, compactness, high sensitivity, and tunable dynamic range, make it a strong candidate in various chemical, biological, and environmental applications.

Antibody engineering-driven controllable chemiluminescence resonance energy transfer for immunoassay with tunable dynamic range

The donor-acceptor distance is a critical factor for the occurrence of chemiluminescent resonance energy transfer (CRET). We herein evaluate the donor-acceptor distance and transfer efficiency of CRET immunoassays of a series of donors which contain different sized antibody fragments, intact monoclonal antibody (IgG), antigen binding fragment (Fab), and single chain fragment antibody (scFv). Core/multishell quantum dots were used as the acceptor in three CRET systems. IgG is the maximum antibody fragment, leading to the longest donor-acceptor distance and the lowest transfer efficiency. Donors with Fab and scFv show significantly decreased distance and increased transfer efficiency. These results suggest an inverse correlation between donor size and transfer efficiency and can be used to provide guidance for the construction of controllable CRET. By combining the controllable CRET with immunoassay, we further develop a tunable sulfamethazine analytical system. Three different sized donors based CRET immunoassay show a markedly different sensitivity and dynamic range. Such adjustable detection provides greater flexibility for contaminant detection in different foodstuffs with different residue limits. This work not only illustrates the effect of donor-acceptor distance on regulating the energy transfer efficiency of CRET system, but also provides a guideline for the construction of a tunable immunoassay.

A novel ratiometric MALDI-MS quantitation strategy for alkaline phosphatase activity with a homogeneous reaction and a tunable dynamic range

A unique ratiometric MALDI-MS strategy is proposed for the convenient and reliable quantitation of alkaline phosphatase based on the homogeneous enzymatic cleavage of a coded phosphopeptide (CPP)-triggered double-signal output. The dynamic range can be tuned by simply adjusting the primary concentration of CPP. The proposed strategy is also capable of being challenged by real human serum, and thus it may offer a wonderful approach for the convenient identification and quantitation of various enzyme activities in clinical diagnosis.

On the utility of RNA sample pooling to optimize cost and statistical power in RNA sequencing experiments

BackgroundIn gene expression studies, RNA sample pooling is sometimes considered because of budget constraints or lack of sufficient input material. Using microarray technology, RNA sample pooling strategies have been reported to optimize both the cost of data generation as well as the statistical power for differential gene expression (DGE) analysis. For RNA sequencing, with its different quantitative output in terms of counts and tunable dynamic range, the adequacy and empirical validation of RNA sample pooling strategies have not yet been evaluated. In this study, we comprehensively assessed the utility of pooling strategies in RNA-seq experiments using empirical and simulated RNA-seq datasets.ResultThe data generating model in pooled experiments is defined mathematically to evaluate the mean and variability of gene expression estimates. The model is further used to examine the trade-off between the statistical power of testing for DGE and the data generating costs. Empirical assessment of pooling strategies is done through analysis of RNA-seq datasets under various pooling and non-pooling experimental settings. Simulation study is also used to rank experimental scenarios with respect to the rate of false and true discoveries in DGE analysis. The results demonstrate that pooling strategies in RNA-seq studies can be both cost-effective and powerful when the number of pools, pool size and sequencing depth are optimally defined.ConclusionFor high within-group gene expression variability, small RNA sample pools are effective to reduce the variability and compensate for the loss of the number of replicates. Unlike the typical cost-saving strategies, such as reducing sequencing depth or number of RNA samples (replicates), an adequate pooling strategy is effective in maintaining the power of testing DGE for genes with low to medium abundance levels, along with a substantial reduction of the total cost of the experiment. In general, pooling RNA samples or pooling RNA samples in conjunction with moderate reduction of the sequencing depth can be good options to optimize the cost and maintain the power.

Graphene-nucleic acid biointerface-engineered biosensors with tunable dynamic range.

Programmed biosensors with tunable quantification range and sensitivity would greatly broaden their application in medical diagnosis, food safety and environmental analysis. Herein, we proposed a graphene-nucleic acid biointerface-engineered biosensor, allowing target molecules to be detected with adjustable dynamic ranges and sensitivities. The biosensors were programmed by simply tuning the poly A tail of aptamer probes. The tuning of the poly A tail would allow the interaction between aptamer probes and graphene oxide (GO) to be modulated, in turn programing the competitive binding processes of aptamer probes to target molecules and GO. The biosensors, termed affinity-tunable aptasensors (atAptasensors) could be easily tuned with different dynamic ranges by using aptamer probes with different tail lengths, and the dynamic range could be extended to be over 3 orders by a combined use of multiple aptamer probes. Remarkably, the specificity of aptamer probes could be increased by increasing the interaction between aptamer probes and GO. Reliability of atAptasensor for ATP detection was tested in serum and milk samples, and we also applied atAptasensor for culture-independent analysis of microorganism pollution.

Vertically Aligned WS2 Layers for High‐Performing Memristors and Artificial Synapses

AbstractInspired by the human brain, the quest for high‐performing neuromorphic architecture has recently gained more attention, which can be achieved by two‐terminal memristors. However, due to random and uncontrolled filament formation during a typical switching process, conventional memristors suffer from severe shortcomings such as temporal/spatial reproducibility as well as trivial sensitivity against applied spikes, however all these properties are crucial for accurate and quick information processing. Here, reproducible and robust two serially connected memristors comprised of ZnO and vertically grown WS2 layers are reported. The device demonstrates remarkable tunable dynamic range along with comprehensive synaptic functions, including short‐ to long‐term plasticity, paired‐pulse facilitation, and spike‐timing‐dependent plasticity. Vertically aligned WS2 layers confine the conduction along 1D channel and drastically enhance the performance. The dynamic processes of memorizing and forgetting are mimicked through a 3 × 3 memristive synapse array. A unique platform to design high‐performing and reproducible artificial synapses for neuromorphic computing is provided.

Direct Blue Light-Induced Autocatalytic Oxidation of o-Phenylenediamine for Highly Sensitive Visual Detection of Triaminotrinitrobenzene.

o-Phenylenediamine (OPD)-based chromogenic reactions are worthy tools for the development of visual colorimetric assays. The chromogenic reactions are usually triggered by various oxidants, which is not easily tunable and incompatible with some analytes. Herein, we report that direct blue light irradiation can induce the autocatalytic oxidation of OPD to generate 2,3-diaminophenazine (oxidized-state OPD, oxOPD). The autocatalytic photo-oxidation reaction mechanism of OPD is mainly ascribed to the resonant energy transfer between ectronically excited oxOPD and dissolved oxygen to form singlet state oxygen with a high oxidation capacity, which accelerates the oxidation of OPD. We demonstrate that under neutral and alkaline environment, the photoinduced autocatalytic oxidation of OPD is able to be further enhanced by triaminotrinitrobenzene (TATB) explosive because of its inhibition effect on the aggregation caused quenching phenomenon of oxOPD. On this basis, a straightforward visual colorimetric assay for TATB with a tunable dynamic range is developed. This assay is capable of detecting TATB explosive concentrations as low as 2.7 nM. Notably, the obvious color change after addition of TATB enables a naked-eye readout with the lowest detectable TATB concentrations of 60 nM.