Nanochannel-based Sensors Research Articles

Super-assembled periodic mesoporous organosilica membranes with hierarchical channels for efficient glutathione sensing.

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 μM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.

Metal-Organic Framework-Decorated Nanochannel Electrode: Integration of Internal Nanoconfined Space and Outer Surface for Small-Molecule Sensing.

Ionic current measurement has been the dominant signaling strategy in nanochannel-based sensors. However, the direct probing of the capture of small molecules is still challenging, and the sensing potential of the outer surface of nanochannels is always ignored. Here, we report the fabrication of an integrated nanochannel electrode (INCE) with nanoporous gold layers modified on two sides of nanochannels, and its application for small-molecule analysis was explored. Metal-organic frameworks (MOFs) were decorated inside and outside of nanochannels, enabling the reduction of pore size to several nanometers, which is among the thickness range of the electric double layer for confined ion diffusion. Combined with excellent adsorption characteristics of MOFs, the developed nanochannel sensor successfully constructed the internal nanoconfined space that could directly capture small molecules and instantly generate a current signal. The contribution of the outer surface and the internal nanoconfined space to diffusion suppression to electrochemical probes was investigated. We found that the constructed nanoelectrochemical cell was sensitive in both the inner channel and the outer surface, signifying a novel sensing mode with integration of the internal nanoconfined space and the outer surface of nanochannels. The MOF/INCE sensor showed excellent performance toward tetracycline (TC) with a detection limit of 0.1 ng·mL-1. Subsequently, sensitive and quantitative detection of TC down to 0.5 μg·kg-1 was achieved in actual chicken samples. This work may open up a new model of nanoelectrochemistry and provide an alternative solution in the field of nanopore analysis for small molecules.

Bio-inspired Track-Etched Polymeric Nanochannels: Steady-State Biosensors for Detection of Analytes.

Bio-inspired polymeric nanochannel (also referred as nanopore)-based biosensors have attracted considerable attention on account of their controllable channel size and shape, multi-functional surface chemistry, unique ionic transport properties, and good robustness for applications. There are already very informative reviews on the latest developments in solid-state artificial nanochannel-based biosensors, however, which concentrated on the resistive-pulse sensing-based sensors for practical applications. The steady-state sensing-based nanochannel biosensors, in principle, have significant advantages over their counterparts in term of high sensitivity, fast response, target analytes with no size limit, and extensive suitable range. Furthermore, among the diverse materials, nanochannels based on polymeric materials perform outstandingly, due to flexible fabrication and wide application. This compressive Review summarizes the recent advances in bio-inspired polymeric nanochannels as sensing platforms for detection of important analytes in living organisms, to meet the high demand for high-performance biosensors for analysis of target analytes, and the potential for development of smart sensing devices. In the future, research efforts can be focused on transport mechanisms in the field of steady-state or resistive-pulse nanochannel-based sensors and on developing precisely size-controlled, robust, miniature and reusable, multi-functional, and high-throughput biosensors for practical applications. Future efforts should aim at a deeper understanding of the principles at the molecular level and incorporating these diverse pore architectures into homogeneous and defect-free multi-channel membrane systems. With the rapid advancement of nanoscience and biotechnology, we believe that many more achievements in nanochannel-based biosensors could be achieved in the near future, serving people in a better way.

Aptamer Self-Assembly-Functionalized Nanochannels for Sensitive and Precise Detection of Chloramphenicol.

Sensitive and precise determination of chloramphenicol (CAP) is of great significance for human health due to its high risk in trace amounts. Solid-state artificial nanochannels are expected to be highly promising sensing devices owing to single-molecule sensitivity, target-specific selectivity, and portability. Herein, we report an aptamer self-assembly-functionalized artificial nanochannel-based sensor for highly sensitive and precise determination of CAP. Aptamer self-assembly (AAs) served as the specific recognition component and were in situ grown on the surface of stable anodic aluminum oxide (AAO) nanochannels to develop an AAs@AAO nanochannel-based sensor. Selective interaction with CAP led to the disassembly of AAs and sensitive current change of AAs@AAO nanochannels, allowing sensitive and precise sensing of CAP in complex food samples. The developed AAs@AAO nanochannel-based sensor showed a wide linear range from 0.32 to 1600 pg. mL-1, low limit of detection (LOD) of 0.1 pg. mL-1, high precision with relative standard deviation of 2.9%, and quantitative recoveries of 93.4-102.2% for CAP in milk, milk powder, and honey samples. This work proposes a versatile nanochannel-based platform for facile, sensitive, and precise sensing of hazardous residues in food samples.

Engineering a Smart Nanofluidic Sensor for High-Performance Peroxynitrite Sensing through a Spirocyclic Ring Open/Close Reaction Strategy.

Peroxynitrite (ONOO-) is an important reactive oxygen/nitrogen species that participates in a range of physiological and pathological processes by modulating ion flux through biological channels. Inspired by a ONOO--regulated K+ channel in vivo, herein, we describe the construction of a smart ONOO--driven nanosensor using a spirocyclic ring open/close reaction approach. The prepared nanosensor possessed a prominent ONOO- selectivity and sensitivity and rapid response (∼90 s) owing to the specific reaction between ONOO- and ligands on the nanosensor surface with a high ion rectification ratio (∼10) and ion gating ratio (∼4). Moreover, this nanosensor system also exhibits excellent stability and recyclability. Thus, these results will provide a new direction for the design of nanochannel-based sensors for future practical and biological applications.

Revealing the Critical Role of Probe Grafting Density in Nanometric Confinement in Ionic Signal via an Experimental and Theoretical Study

The grafting density of probes at sensor interface plays a critical role in the performance of biochemical sensors. However, compared with macroscopic interface, the effects of probe grafting density at nanometric confinement are rarely studied due to the limitation of precise grafting density regulation and characterization at the nanoscale. Here, we investigate the effect from the grafting density of DNA probes on ionic signal for nucleic acid detection in a cylindrical nanochannel array (with diameter of 25 nm) by combing experiments and theories. We set up a theoretical model of charge distribution from close to inner wall of nanochannels at low probe grafting density to spreading in whole space at high probe grafting density. The theoretical results fit well with the experimental results. A reverse of ionic output from signal-off to signal-on occurs with increasing probe grafting density. Low probe grafting density offers a high current change ratio that is further enhanced using long-chain DNA probes or the electrolyte with a low salt concentration. This work develops an approach to enhance performance of nanochannel-based sensors and explore physicochemical properties in nanometric confines.

Nanochannel-based sensor for the detection of lead ions in traditional Chinese medicine.

Lead ions (Pb2+) are used in the quality control of traditional Chinese medicine (TCM) preparations because they are highly toxic to human health. At present, sophisticated analytical instrumentation and complicated procedures for sample analysis are needed for the determination of Pb2+. Herein, a simple, fast, and sensitive peptide-modified nanochannel sensor to detect Pb2+ in TCM is reported, which is based on a Pb2+-specific peptide modified porous anodized aluminum membrane (PAAM). This peptide-based nanochannel clearly has the highest selectivity for Pb2+ when compared to other heavy metal ions, including As2+, Cd3+, Co2+, Cr2+, Cu2+, Fe3+, Hg2+, Mg2+, Mn2+, Ni2+, and Zn2+. Based on linear ranges from 0.01 to 0.16 μM and 10 to 100 μM, the detection limit was calculated to be 0.005 μM. Moreover, this peptide-based nanochannel sensor was successfully used to detect Pb2+ in complex TCM samples. In addition, when compared with the gold standard atomic absorption spectrophotometry (AAS) method, the recovery of the peptide-modified nanochannel sensor was between 87.7% and 116.8%. The experimental results prove that this new sensor is able to achieve accurate detection of Pb2+ in TCM samples. Thus, this sensor system could provide a simple assay for sensitive and selective detection of Pb2+ in TCM, thereby showing great potential in the practical application for the quality control of heavy metals in TCM.

Construction of a Smart Nanofluidic Sensor through a Redox Reaction Strategy for High-Performance Carbon Monoxide Sensing.

Carbon monoxide (CO), an important gas signaling molecule, demonstrated various physiological and pathological functions by regulating the ion flux of biological channels. Herein, inspired by the CO-regulated K+ channel in vivo, we propose a smart CO-responsive nanosensor through the redox reaction strategy. Such nanosensor demonstrated an outstanding CO specificity and selectivity with high ion rectification (∼9) as well as excellent stability and recyclability. Therefore, these results will provide a new direction for the design of nanochannel-based sensors for future practical and biological applications.

A capacitive-pulse model for nanoparticle sensing by single conical nanochannels.

Nanochannel based devices have been widely used for single-molecule detection. The detection usually relies on the resistive-pulse model, where the change of the monitored current depends on the physical volumetric blocking of the nanochannel by the analyte. However, this mechanism requires that the nanochannel diameter should not be much larger than the analyte size, because, otherwise, the resultant current change would be too small to detect, and therefore poses particular challenges for the fabrication of nanochannels. To circumvent this issue, in this report, we propose a different mechanism of capacitive-pulse model, where the transport signals can be significantly magnified by the capacitive effect of the nanochannel. We experimentally demonstrate that current pulses with an averaged peak height of 0.87 nA can be achieved for transporting 60 nm nanoparticles through a conical nanochannel device, whereas the traditional resistive-pulse model only predicts one-order-of-magnitude lowered value. With further comprehensive simulation, the dependence of this effect on the nanochannel geometry as well as the surface charge density for both the nanochannel and the analyte is predicted, which would provide important guidance for better designing of the nanochannel-based sensors.

How Does Confinement Change Ligand-Receptor Binding Equilibrium? Protein Binding in Nanopores and Nanochannels.

We present systematic studies for the binding of small model proteins to ligands attached to the inner walls of long nanochannels and short nanopores by polymeric tethers. Binding of proteins to specific ligands inside nanometric channels and pores leads to changes in their ionic conductance, which have been exploited in sensors that quantify the concentration of the proteins in solution. The theoretical predictions presented in this work are aimed to provide a fundamental understanding of protein binding under geometrically confined environments and to guide the design of this kind of nanochannel-based sensors. The theory predicts that the fraction of the channel volume filled by bound proteins is a nonmonotonic function of the channel radius, the length of the tethers, the surface density of the ligands and the size of the proteins. Notably, increasing the density of ligands, decreasing the size of the channel or increasing the size of the protein may lead to a decrease of the fraction of the channel volume filled by bound proteins. These results are explained from the incomplete binding of proteins to the ligands due to repulsive protein-protein and protein-ligand steric interactions. Our work suggests strategies to optimize the change in conductance due to protein binding, for example: (i) proteins much smaller than the radius of the channel may effectively block the channel if tethers of appropriate length are used, and (ii) a large decrease in conductance upon protein binding can be achieved if the channel and the protein are oppositely charged.

Controlling the motion of DNA in a nanochannel with transversal alternating electric voltages

A nanofluidic channel, with a pair of perpendicularly aligned nanoelectrodes, is proposed to electrically control the motion of DNA molecules. Using all-atom molecular dynamics simulations, we studied electrostatic responses of a charged DNA molecule in the nanochannel and investigated optimized operating conditions for controlling the DNA molecule. When the transversal electric field was periodically turned on and off, the DNA molecule was correspondingly immobilized on and released from the channel surface. Under simultaneously applied longitudinal biasing and transversal trapping electric fields, the DNA molecule moved forward in a ‘ratchet’-like fashion. It is expected that achieving the controlled motion of DNA in the channel can advance studies and applications of a nanochannel-based sensor for analyzing DNA (e.g., DNA sequencing).

Controlling Motion of DNA in a Nanochannel with Transverse Alternating-Electric-Voltages

One key requirement for fast and accurate DNA sequencing in nanopores or nanochannels is to control the DNA position and modulate the speed, which, however, still remains a big challenge. Because of drastically changed electric potentials across a nanochannel, the DNA motion is too rapid for a sensor to detect each DNA nucleotide. A nanofluidic channel, with a pair of perpendicularly aligned nanoelectrodes, is proposed to electrostatically control the motion of DNA molecules. Using all-atom molecular dynamics simulations, we studied electrostatic responses of a charged DNA molecule in the nanochannel and investigated optimized operating conditions for controlling the motion of the DNA. When the transverse electric field was periodically turned on and off, the DNA molecule was correspondingly immobilized on and released from the channel surface. Under simultaneously applied longitudinal biasing and transverse trapping electric fields, the DNA molecule moved forward in a “ratchet”-like fashion. It is expected that achieving the controlled motion of DNA in the channel can advance studies and applications of a nanochannel-based sensor for analyzing DNA (e.g., DNA sequencing).

Cellular level classification of breast cancer through proteomic markers using nanochannel array sensors.

A nanochannel-based sensor for cellular level classification of breast cancer metastasis has been designed. Our approach to the classification of cell's likelihood to metastasize is based on screening for levels of expression of specific proteomic biomarkers associated with breast cancer stem cells. Proteomic activity for four breast cancer cell lines for three specific markers (PDGFR, ALDH1A1 and ALDH1A3) was quantified. The nanochannel sensor is an electrochemical immunoassay and comprises of alumina nanochannel arrays integrated on to a gold microelectronic platform. The sensor operates on the principle of electrochemical impedance spectroscopy. Test cell lysate samples from SUM159 invasive, SUM159 noninvasive, HC1143 and DCIS cell lines were classified as those having a high likelihood of metastases based on the levels of proteomic activity evaluated against the three key markers. The lowest proteomic activity measured was 0.1 ng/ml with PDGFR, 100 ng/ml with ALDH1A1 and 100 ng/ml with ALDH1A3, correlating to the detection of unit stem cell count. Original submitted 9 November 2012; Revised submitted 29 July 2013.