Nanopore Arrays Research Articles

Profiling Phenotypic Heterogeneity of Circulating Tumor Cells through Spatially Resolved Immunocapture on Nanoporous Micropillar Arrays.

The phenotype of circulating tumor cells (CTCs) offers valuable insights into monitoring cancer metastasis and recurrence. While microfluidics presents a promising approach for capturing these rare cells in blood, the phenotypic profiling of CTCs remains technically challenging. Herein, we developed a nanoporous micropillar array chip enabling highly efficient capture and in situ phenotypic analysis of CTCs through enhanced and tunable on-chip immunoaffinity binding. The nanoporous micropillar array addresses the fundamental limits in fluidic mass transfer, surface stagnant flow boundary effect, and interface topographic and multivalent reactions simultaneously within a single device, resulting in a synergistic enhancement of CTC immunocapture efficiency. The CTC capture efficiency increased by approximately 40% for cancer cells with low surface marker expressing. By manipulating fluidic velocity (hydrodynamic drag force) on the chip, a cell adhesion gradient was generated in the capture chamber, enabling individual CTCs with varying expression levels of epithelial cellular adhesion molecules to be immunocaptured at the corresponding spatial locations where equilibrium drag force is provided. The clinical utility of the nanoporous micropillar array was demonstrated by accurately distinguishing early and advanced stages of breast cancer and further longitudinally monitoring treatment response. We envision that the nanoporous micropillar array chip will provide an in situ capture and molecular profiling approach for CTCs and enhance the clinical application of CTC liquid biopsy.

Research on high-quality factor sensing characteristics of all-dielectric nanopore array metasurface based on POA-DELM

Abstract Based on the optical properties of symmetric structures independent of each other in the orthogonal direction, an all-dielectric nano-square hole array metasurface which is symmetric along the diagonal is proposed. By changing the size of square nanopores, the symmetry of the periodic unit structure is broken and the double Fano resonance can be excited. The influence of each structural parameter on the sensing performance of the metasurface is analyzed respectively. As the main structural parameters and performance index, the metasurface height and the lengths of the main and sub-diagonal square nanoholes are selected as the input parameters, and the figure of merit (FOM) value is used as the output value. Then the nonlinear mapping relationship between the input and the output is established through deep extreme learning machine (DELM). Different optimization algorithms are used to optimize the weighted FOM values globally. The four evaluation indicators including root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and model fit (R-squared, R2) are used to assess the training effectiveness of the model. It is shown that the indexes are 0.9986, 0.9725, 3.1612 and 0.9733 respectively, and the FOM values of the dual Fano resonance after pelican optimization algorithm ( POA ) optimization are as high as 9.88 × 103 and 1.28 × 105, which demonstrate the effectiveness of POA-DELM proposed in this paper.

Electroosmotic Flow-Driven DNA-CNT Nanomotor via Tunable Surface-Charged Nanopore Array.

Nanomotors are usually designed to work in liquid media and carry cargo; they exhibit excellent potential for biosensing and disease treatment applications due to their small size. Graphene and carbon nanotubes (CNTs) are crucial components of rotary nanomotors because of excellent mechanical properties and adaptability to the human body. Herein, we introduce a DNA-CNT-based nanomotor that achieves its rotational control through an array of nanopores with tunable surface charges. The findings demonstrate that by adjusting the surface charge density of the nanopores and the direction of electric field, a DNA strand can be sequentially captured by the nanopores, thereby rotating the connected CNT. The transition from a four-nanopore array to a six-nanopore array reveals that reducing the step angle to 60° significantly enhances the rotational stability of the nanomotor and reduces random fluctuations caused by Brownian motion. This method improves the control stability of the nanomotor, providing robust support for future applications in nanoscale manipulation.

Modular Plasmonic Nanopore for Opto‐Thermal Gating

AbstractSolid‐state nanopore gating inspired by biological ion channels is gaining increasing traction due to a large range of applications in biosensing and drug delivery. Integration of stimuli‐responsive molecules such as poly(N‐isopropylacrylamide) (PNIPAM) inside nanopores can enable temperature‐dependent gating, which so far has only been demonstrated using external heaters. In this work, plasmonic resonators are combined inside the nanopore architecture with PNIPAM to enable optical gating of individual or multiple nanopores with micrometer resolution and a switching speed of a few milliseconds by thermo‐plasmonics effects. A temperature change of 40 kelvin per millisecond is achieved and demonstrates the efficacy of this method using nanopore ionic conductivity measurements that enable selective activation of individual nanopores in an array. Moreover, the selective gating of specific nanopores in an array can set distinct ionic conductance levels: low, medium, and high (i.e., “0,” “1,” and “2”), which can be exploited for logical gating with optical signal control. Such selective optical gating in nanopore arrays marks a breakthrough in nanofluidics, as it paves the way toward smart devices that offer multifunctional applications including biosensing, targeted drug delivery, and fluidic mixing.

Facile Fabrication of Hierarchical Structured Anodic Aluminum Oxide Molds for Large-Scale Production of Superhydrophobic Polymer Films.

Anodized aluminum oxide (AAO) molds were used for the production of large-area and inexpensive superhydrophobic polymer films. A controlled anodization methodology was developed for the fabrication of hierarchical micro-nanoporous (HMN) AAO imprint molds (HMN-AAO), where phosphoric acid was used as both an electrolyte and a widening agent. Heat generated upon repetitive high-voltage (195 V) anodization steps is effectively dissipated by establishing a cooling channel. On the HMN-AAO, within the hemispherical micropores, arrays of hexagonal nanopores are formed. The diameter and depth of the micro- and nanopores are 18/8 and 0.3/1.25 µm, respectively. The gradual removal of micropatterns during etching in both the vertical and horizontal directions is crucial for fabricating HMN-AAO with a high aspect ratio. HMN-AAO rendered polycarbonate (PC) and polymethyl methacrylate (PMMA) films with respective water contact angles (WCAs) of 153° and 151°, respectively. The increase in the WCA is 80% for PC (85°) and 89% for PMMA (80°). On the PC and PMMA films, mechanically robust arrays of nanopillars are observed within the hemispherical micropillars. The micro-nanopillars on these polymer films are mechanically robust and durable. Regular nanoporous AAO molds resulted in only a hydrophobic polymer film (WCA = 113-118°). Collectively, the phosphoric acid-based controlled anodization strategy can be effectively utilized for the manufacturing of HMN-AAO molds and roll-to-roll production of durable superhydrophobic surfaces.

PH and potential-controlled multi-modal mass transport in block copolymer nanochannel membranes

Inspired by the hydrophobic gating for achieving fast and selective ion/molecular transport in cell membranes, wetting/dewetting transition in solid-state nanopores controlled by external stimuli such as voltage, pH, electrostatics, and light have attracted increasing attention. For an accurate and better understanding, a single nanopore or low-density array of nanopores was preferred to investigate the wetting and dewetting transitions owing to their well-defined chemical functions and physical structures. However, high-density nanochannel membranes capable of processing high-throughput and multi-modal mass transport are more beneficial with the aim of practical use. In this regard, pH- and potential-responsive nanochannel membranes consisting of a polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer (BCP) are prepared to demonstrate a multi-modal transport system with high-throughput capability. At pH < pKa(P4VP) (pKa ∼ 4.8), the cylindrical P4VP nanodomains are hydrophilic and positively charged, acting as an anion-exchange membrane. In contrast, at pH > pKa(P4VP), the P4VP domains switch to be charge-neutral and hydrophobic, naturally blocking the mass transport through the nanochannels. Applying a sufficiently positive potential to a BCP membrane-coated electrode may induce oxidative wetting in the hydrophobic nanochannels to facilitate mass transport across the membrane with no charge-selectivity. Releasing the bias makes the hydrophobic nanochannel membranes retrieve the original dewetted state, blocking the transport again. In addition, direct observation of the wetting-dewetting transition dynamics in the hydrophobic nanochannels is investigated by monitoring potential-correlated electrochemiluminescence (ECL) signals arising from Ru(bpy)32+ and co-reactant tripropylamine (TPA) under potential modulations. ECL signals tend to decrease with increasing membrane thickness ranging from 0 nm to 820 nm because it requires higher potentials to induce wetting in the nanochannels due to elongated hydrophobic nanochannels. The multi-modal transport system developed in the present work will be useful for applications such as water treatment, biosensors, and smart valve systems like controlled drug release/delivery.

Fabrication of arrayed V-shape micro-nano hierarchical structures for dew collection

Planer 2D nanopore arrays of porous anodic alumina can be unfolded to designed 3D arrayed micro-nano hierarchical structures by a programmed anisotropic electrochemical anodization, which consists of programed polymer masking and stepped anodization. Arrayed symmetrical and asymmetrical V-shape tiered micro grooves with nanotip-capped nanopore structures are respectively custom tailored to obtain high-efficiency dew collection. It is found that symmetrical V-shape tiered micro grooves with nanotip-capped nanopore structures show collection efficiency (36.176 ± 3.832 mg cm−2 h−1) twice as much as that of pure nanostructured surface, where the environment temperature is ∼18 °C, the relative humidity is ∼86 % and the sample temperature is ∼5 °C. Owning to the larger dew nucleation area, low solid-liquid adhesion and faster dew growth rate, the jumping micro-dews quickly gather and growth to big dews at the bottom of the V-shape tiers as the samples horizontally placed, which can easily fall off as turn the samples to vertical. Due to the simple equipment, low cost and large-area fabrication ability, these arrayed micro-nano hierarchical structures not only have potential to become high efficiency dew collector but also could be a platform for the controlled preparation of 3D complicated micro-nano structures of various materials with advanced functions.

High Sensitivity and Specificity Platform to Validate MicroRNA Biomarkers in Cancer and Human Diseases.

We developed a technology for detecting and quantifying trace nucleic acids using a bracketing protocol designed to yield a copy number with approximately ± 20% accuracy across all concentrations. The microRNAs (miRNAs) let-7b, miR-15b, miR-21, miR-375 and miR-141 were measured in serum and urine samples from healthy subjects and patients with breast, prostate or pancreatic cancer. Detection and quantification were amplification-free and enabled using osmium-tagged probes and MinION, a nanopore array detection device. Combined serum from healthy men (Sigma-Aldrich, St. Louis, MO, USA #H6914) was used as a reference. Total RNA isolated from biospecimens using commercial kits was used as the miRNA source. The unprecedented ± 20% accuracy led to the conclusion that miRNA copy numbers must be normalized to the same RNA content, which in turn illustrates (i) independence from age, sex and ethnicity, as well as (ii) equivalence between serum and urine. miR-21, miR-375 and miR-141 copies in cancers were 1.8-fold overexpressed, exhibited zero overlap with healthy samples and had a p-value of 1.6 × 10-22, tentatively validating each miRNA as a multi-cancer biomarker. miR-15b was confirmed to be cancer-independent, whereas let-7b appeared to be a cancer biomarker for prostate and breast cancer, but not for pancreatic cancer.

In-Situ Gas Permeation-Driven Ionic Current Rectification of Heterogeneously Charged Nanopore Arrays.

Ionic diodes provide ionic current rectification (ICR), which is useful for micro-/nanofluidic devices for ionic current-mediated applications. However, the modulation of ICR is not fully developed, and current challenges include limited active control and localized modulation for further multiplexing of micro-/nanofluidic ionic diodes. Herein, a microfluidic device integrated with particle-assembly-based ionic diodes (PAIDs) and a gas-flow channel above them is presented. Exploiting in-situ gas permeation through a polymeric film, precise control over the physiochemical conditions of the nanopores within the PAIDs, leading to the modulation of ICR is demonstrated. The investigation not only characterizes the rectification properties of the PAIDs but also unveils their capacitor-like behavior and the ability to actively modulate ICR using various gas flows. Furthermore, the reversible modulation of ICR through dynamic switching of gas-dissolved solutions, enabling ion-signal amplification is showcased. This pioneering approach of in situ gas-permeation offers programmable manipulation of ion transport along PAIDs, thereby positioning ionic diodes as versatile nanofluidic components. Looking ahead, the development of multiplexed PAIDs in an addressable manner on a chip holds promise for practical applications across diverse fields, including ion signaling, ion-based logic, chemical reactors, and (bio)chemical sensing.

Nanopore Blockade Sensors for Quantitative Analysis Using an Optical Nanopore Assay.

Nanopore sensing is a popular biosensing strategy that is being explored for the quantitative analysis of biomarkers. With low concentrations of analytes, nanopore sensors face challenges related to slow response times and selectivity. Here, we demonstrate an approach to rapidly detect species at ultralow concentrations using an optical nanopore blockade sensor for quantitative detection of the protein vascular endothelial growth factor (VEGF). This sensor relies on monitoring fluorescent polystyrene nanoparticles blocking nanopores in a nanopore array of 676 nanopores. The fluorescent signal is read out using a wide-field fluorescence microscope. Nonspecific blockade events are then distinguished from specific blockade events based on the ability to pull the particles out of the pore using an applied electric field. This allows the detection of VEGF at sub-picomolar concentration in less than 15 min.

Nanopore arrays with TMOKE-enhanced high performance sensing

Magneto-plasmon sensing structure based on surface plasmon resonance (SPR) and magneto-optical (MO) effect has become a hot research topic in recent years. In this work, we propose a magneto-plasmon crystal consisting of an Au/Co double-layer nanoporous structure with optically thick Au film as a substrate. Due to the excitation of high-quality SPR, a Fano-like transverse magneto-optical Kerr (TMOKE) spectrum with subnanometer bandwidth is realized. A sensitivity of up to 677 nm RIU−1 is detected under subtle refractive index changes in air, and all the calculated figure of merits (FOM) are higher than 104 RIU−1. In addition, in order to highlight the superiority of the sensing performance of the MO plasmon (MOSPR) sensor, we compare the MOSPR sensor with the SPR sensor and calculate their FOM in different refractive index environments. The results show that the FOM of the MOSPR sensor is two orders of magnitude higher than that of the SPR sensor, which proves that the performance of the MOSPR sensor is significantly better than that of the SPR sensor and provides a theoretical basis for biosensing and gas detection based on magneto plasmon.

High-Sensitivity Photoelectrochemical Ultraviolet Photodetector with Stable pH-Universal Adaptability Based on Whole Single-Crystal Integrated Self-Supporting 4H-SiC Nanoarrays.

Emerging photoelectrochemical (PEC) photodetectors (PDs) have notable advantages over conventional PDs and have attracted extensive attention. However, harsh liquid environments, such as those with high corrosivity and attenuation, substantially restrict their widespread application. Moreover, most PEC PDs are constructed by assembling numerous nanostructures on current collector substrates, which inevitably contain abundant interfaces and defects, thus greatly weakening the properties of PDs. To address these challenges, a high-performance pH-universal PEC ultraviolet (UV) PD based on a whole single-crystal integrated self-supporting 4H-SiC nanopore array photoelectrode is constructed, which is fabricated using a two-step anodic oxidation approach. The PD exhibits excellent photodetection behavior, with high responsivity (218.77mAW-1), detectivity (6.64×1013Jones), external quantum efficiency (72.47%), and rapid rise/decay times (17/48ms) under 375nm light illumination with a low intensity of 0.15mWcm-2 and a bias voltage of 0.6V, which is fall in the state-of-the-art of the wide-bandgap semiconductor-based PDs reported thus far. Furthermore, the SiC PEC PD exhibits excellent photoresponse and long-term operational stability in pH-universal liquid environments. The improved photodetection performance of the SiC PEC PD is primarily attributed to the synergistic effect of the nanopore array structure, integrated self-supporting configuration, and single-crystal structure of the whole photoelectrode.

Efficient V-Shaped Substrate for Surface and Volume Enhanced Raman Spectroscopic Analysis of Bioaerosol: Prevention from Potential Health Risk.

Bioaerosols pose a great threat to human life and health, and developing highly efficient and accurate identification and analysis methodologies for bioaerosols provides prerequisite knowledge to evaluate their toxicity on human health. In this paper, a rapid and economical method is proposed for the detection of bioaerosols based on surface-enhanced Raman scattering (SERS). The SERS substrate was prepared using an anodic aluminum oxide (AAO) template with an inverted conical (V-shaped) nanopore array structure that was subsequently deposited with Ag nanoparticles (AgNPs) through magnetron sputtering. This tailored nanostructure essentially enables the differentiated and efficient detection of Escherichia coli and Staphylococcus epidermidis health risks within 10 min, along with corresponding detection limits of 103 cells/mL and 104 cells/mL, respectively. Notably, by comparing the Raman spectrum of the two bacteria obtained from the plain plane deposited with the same AgNPs, the V-shaped nanopore array structure provides a more robust enhancement effect in the Raman signal relative to the ordinary plane. More importantly, the applicability of developed AgNPs@V-shaped AAO SERS substrate was validated using ambient bioaerosols, thus emphasizing the great potential of the application of SERS-based technique for a cost-effective, rapid label-free and culture-free bioaerosol analysis without experiencing conventional time-consuming and laborious incubation processes.

Surface modification strategies of 304 austenitic stainless steel plate with different micromorphology and composition for improved mechanical interlocking and chemical bonding in metal–epoxy joints

304 austenitic stainless-steel (SS) strip-based carbon fiber metal laminates (CFMLs) have raised significant concerns, in terms of their mechanical performance. On top of that, the hybrid laminates’ interlamination performance is vital in regulating their failure patterns. Along these lines, in this work, SS strips with regulatable micromorphology and composition were obtained by using physical and chemical surface modification strategies, including polishing, acid etching, anodization, and thermal treatment. The shear strength of the treated-SS/epoxy single lap joints (two treated-SS strips bonded by the epoxy resin via hot curing process) was systematically explored, and the origins of the enhancement mechanism were attributed to the resulting surface microstructure, as well as the possible chemical reactions between the treated surface and the curing agent. The etching-anodizing-thermally treated-SS (EAT-SS)/epoxy joint exhibited the maximum shear strength (16.04 MPa) and work of fracture (5.85 kJ·m−2) due to the substantial cohesive failure pattern of the epoxy. The encouraging enhancement was mainly attributed to the synergistic effect of the micro-annular pit and the nanoporous array structure of the EAT-SS surface. These effects induced a significant mechanical interlock and a plausible chemical reaction at the interface, which led to improved bonding strength between the epoxy and treated-SS surface. Overall, in this work, it was demonstrated that the combination of the anodization and thermal treatment can effectively improve the interlamination bonding properties between the SS strip and the epoxy resin due to the combination effect of mechanical interlocking and chemical bonding.

Memristive Response and Capacitive Spiking in Aqueous Ion Transport through Two-Dimensional Nanopore Arrays.

In living organisms, information is processed in interconnected symphonies of ionic currents spiking through protein ion channels. As a result of dynamic switching of their conductive states, ion channels exhibit a variety of current-voltage nonlinearities and memory effects. Fueled by the promise of computing architectures entirely different from von Neumann, recent attempts to identify and harness similar phenomena in artificial nanofluidic environments focused on demonstrating analogue circuit elements with memory. Here we explore aqueous ionic transport through two-dimensional (2D) membranes featuring arrays of ion-trapping crown-ether-like pores. We demonstrate that for aqueous salts featuring ions with different ion-pore binding affinities, memristive effects emerge through coupling between the time-delayed state of the system and its transport properties. We also demonstrate a nanopore array that behaves as a capacitor with a strain-tunable built-in barrier, yielding behaviors ranging from current spiking to an ohmic response. By focusing on the illustrative underlying mechanisms, we demonstrate that realistically observable memory effects may be achieved in nanofluidic systems featuring crown-porous 2D membranes.

Ion Concentration Polarization Tunes Interpore Interactions and Transport Properties of Nanopore Arrays

AbstractBiological processes require concerted function of many channels embedded in the cell membrane. While single solid‐state nanopores are already designed to mimic properties of individual biological channels, it is not yet known how to connect the pores to achieve biomimetic ionic circuits with interacting components. To identify fundamental processes that control interactions between nanopores embedded in the same membrane, a model system of minimal arrays consisting of two and three nanopores in silicon nitride films is designed. The constituent nanopores have an opening diameter &lt;10 nm, and the interpore spacing is tuned between 15 and 200 nm. The experimental and modeling results reveal that nanopores in an array interact with each other via overlapping depletion zones created by the process of concentration polarization. The interactions can be further controlled by salt concentration and voltage. These results showcase a possibility of tuning interactions between nanopores and transport properties of arrays by chemical modification of the pore walls. Arrays consisting of nanoporous ionic diodes feature depletion zones with higher concentrations, and lower current suppression than homogeneously charged pores. These experiments and modeling provide the first steps to leave the constraints of single nanopores and to design biomimetic ionic circuits.

Ion concentration polarization causes a nearly pore-length-independent conductance of nanopores.

There has been a great amount of interest in nanopores as the basis for sensors and templates for preparation of biomimetic channels as well as model systems to understand transport properties at the nanoscale. The presence of surface charges on the pore walls has been shown to induce ion selectivity as well as enhance ionic conductance compared to uncharged pores. Here, using three-dimensional continuum modeling, we examine the role of the length of charged nanopores as well as applied voltage for controlling ion selectivity and ionic conductance of single nanopores and small nanopore arrays. First, we present conditions where the ion current and ion selectivity of nanopores with homogeneous surface charges remain unchanged, even if the pore length decreases by a factor of 6. This length-independent conductance is explained through the effect of ion concentration polarization (ICP), which modifies local ionic concentrations, not only at the pore entrances but also in the pore in a voltage-dependent manner. We describe how voltage controls the ion selectivity of nanopores with different lengths and present the conditions when charged nanopores conduct less current than uncharged pores of the same geometrical characteristics. The manuscript provides different measures of the extent of the depletion zone induced by ICP in single pores and nanopore arrays, including systems with ionic diodes. The modeling shown here will help design selective nanopores for a variety of applications where single nanopores and nanopore arrays are used.

Nanopore-based glycan sequencing: state of the art and future prospects.

Sequencing of biomacromolecules is a crucial cornerstone in life sciences. Glycans, one of the fundamental biomolecules, derive their physiological and pathological functions from their structures. Glycan sequencing faces challenges due to its structural complexity and current detection technology limitations. As a highly sensitive sensor, nanopores can directly convert nucleic acid sequence information into electrical signals, spearheading the revolution of third-generation nucleic acid sequencing technologies. However, their potential for deciphering complex glycans remains untapped. Initial attempts demonstrated the significant sensitivity of nanopores in glycan sensing, which provided the theoretical basis and insights for the realization of nanopore-based glycan sequencing. Here, we present three potential technical routes to employ nanopore technology in glycan sequencing for the first time. The three novel technical routes include: strand sequencing, capturing glycan chains as they translocate through nanopores; sequential hydrolysis sequencing, capturing released monosaccharides one by one; splicing sequencing, mapping signals from hydrolyzed glycan fragments to an oligosaccharide database/library. Designing suitable nanopores, enzymes, and motors, and extracting characteristic signals pose major challenges, potentially aided by artificial intelligence. It would be highly desirable to design an all-in-one high-throughput glycan sequencer instrument by integrating a sample processing unit, nanopore array, and signal acquisition system into a microfluidic device. The nanopore sequencer invention calls for intensive multidisciplinary cooperation including electrochemistry, glycochemistry, engineering, materials, enzymology, etc. Advancing glycan sequencing will promote the development of basic research and facilitate the discovery of glycan-based drugs and disease markers, fostering progress in glycoscience and even life sciences.

Модификация наноструктурированного диоксида титана методом гидротермальной обработки для улучшения электрических параметров бета-вольтаических элементов

New technologies of microelectronics are emerging to reduce the size of devices and combine them into more compact ultra-low power systems. Betavoltaic power sources (BVPSs) can serve as power generators of such order. BVPSs consist of a combination of betavoltaic cells (BVCs) based on long-lived radioisotopes of beta radiation and semiconductor converters (SCs). One of the key tasks for increasing the power of BVC is the selection of SCs that can efficiently convert the energy of beta particles into electricity. Currently, semiconductor structures with a developed surface and a high band gap are considered to be perspective SCs. In present work, arrays of titanium dioxide nanopores (TiO2 NPs) synthesized by common electrochemical anodization was chosen as a SCs. These SCs were part of BVCs based on nickel-63 with an activity of ~ 10 Ci/g. TiO2 NPs with an amorphous structure in the composition of BVC demonstrated low electrical parameters. To increase them, we modified TiO2 NPs by the hydrothermal method in a solution of Sr(OH)2 with a concentration of 0.05 mol/l at various times. These experiments were carried out in order to convert TiO2 (anatase) into structure-like SrTiO3. We found that the electrical parameters of the SCs increased with the duration of the modification time. The best result was obtained in case of 3 h modification — the BVC generated a short circuit current 2,9 nA, open circuit voltage 0,8 V and had a maximum power 0,8 nW at 0,45 – 0,5 V. The obtained electrical parameters in combination with the miniature dimensions of the BVCs open up the potential possibility of creating a BVPS with an increased power density.

Engineered cortical microcircuits for investigations of neuroplasticity.

Recent advances in neural engineering have opened new ways to investigate the impact of topology on neural network function. Leveraging microfluidic technologies, it is possible to establish modular circuit motifs that promote both segregation and integration of information processing in the engineered neural networks, similar to those observed in vivo. However, the impact of the underlying topologies on network dynamics and response to pathological perturbation remains largely unresolved. In this work, we demonstrate the utilization of microfluidic platforms with 12 interconnected nodes to structure modular, cortical engineered neural networks. By implementing geometrical constraints inspired by a Tesla valve within the connecting microtunnels, we additionally exert control over the direction of axonal outgrowth between the nodes. Interfacing these platforms with nanoporous microelectrode arrays reveals that the resulting laminar cortical networks exhibit pronounced segregated and integrated functional dynamics across layers, mirroring key elements of the feedforward, hierarchical information processing observed in the neocortex. The multi-nodal configuration also facilitates selective perturbation of individual nodes within the networks. To illustrate this, we induced hypoxia, a key factor in the pathogenesis of various neurological disorders, in well-connected nodes within the networks. Our findings demonstrate that such perturbations induce ablation of information flow across the hypoxic node, while enabling the study of plasticity and information processing adaptations in neighboring nodes and neural communication pathways. In summary, our presented model system recapitulates fundamental attributes of the microcircuit organization of neocortical neural networks, rendering it highly pertinent for preclinical neuroscience research. This model system holds promise for yielding new insights into the development, topological organization, and neuroplasticity mechanisms of the neocortex across the micro- and mesoscale level, in both healthy and pathological conditions.