Biomedical Microdevices最新文献

Surface Acoustic Wave (SAW) sensors are pivotal Micro-Electrical-Mechanical Systems (MEMS) devices for micro-particle detection, offering compact design, high throughput, and low fabrication cost. This work presents the design, fabrication, and characterization of a SAW sensor employing a Polydimethylsiloxane (PDMS) microfluidic channel as a dual-function waveguide to effectively localize Love Wave (LW) confinement and convert Rayleigh waves to LW. Utilizing a comprehensive approach integrating multi-parametric Finite Element Analysis (FEA), analytical modeling, and experimental validation, two SAW devices with distinct interdigitated transducer (IDT) electrode configurations (12 μm and 38 μm width and spacing) have been developed. FEA and experimental results consistently confirm the superior performance of the 12 μm electrode configuration. This device achieved significant BAW suppression, evidenced by a low insertion loss (S21) of -57 dB (FEA) and a narrow admittance peak (Δf = 0.6 MHz at FWHM), yielding a high Q-factor at its center frequency (fc = 82.5 MHz). Performance metrics for the 12 μm electrode configuration include a reflection coefficient (S11) of -85 × 10⁻⁷ dB (vs. -40 × 10⁻⁸ dB for 38 μm), experimental insertion losses of -64.86 dB, -67.05 dB, and − 69.27 dB for 50, 40, and 30 finger pairs respectively, and low limit of detection (LoD) with higher number of finger pairs. The PDMS waveguide maximized acoustic energy confinement at the surface, enabling efficient Love wave propagation, which minimizes dissipative losses in Liquids. Moreover, the dominant y-direction surface displacement of 0.026 μm, and a higher admittance peak (80 × 10⁻⁷), indicating high sensitivity in liquid medium and high quality (Q) factor, respectively. The sensor’s micro-particle detection capability, based on monitoring IL changes – established as an effective metric for quantifying particle-induced perturbations in flow-through configurations – across varying particle concentrations, has been experimentally validated using 10 μm diameter Polystyrene (PS) particles as Lactobacillus analogs. The strong agreement between analytical, FEA, and experimental results validates this high-fidelity SAW device with integrated microfluidics as a promising, cost-effective, and highly sensitive platform for micro-particle detection in liquid media, with potential extension to gas sensing applications, if used without any waveguide.

Chromosome-less minicells, derived from aberrant polar division events of bacterial cells, have emerged as promising nanocarriers for targeted cancer drug delivery due to their unique characteristics. A major challenge in their purification process lies in effectively isolating such spherical minicells (< 1 μm) from their rod-shaped parental cells (1–10 μm). This study investigates the use of Deterministic Lateral Displacement (DLD) microfluidic systems for minicell purification, leveraging Two-Photon Lithography (TPL) for the rapid prototyping of high-resolution designs optimized for this purpose. Under laminar flow conditions, we investigated key DLD design parameters including symmetric and asymmetric post gaps, outlet widths, dual post arrays, fluidic-resistance-optimized design. To enhance separation efficiency, we developed a two-stage microfluidic separation system combining a spiral inertial chip and an optimized DLD chip in series. Utilizing high-resolution TPL for chip fabrication of an inertial chip with 12 spirals and an asymmetric DLD chip with a 2 μm downstream post gap, we achieved a separation efficiency of 94%. This high efficiency achieved using microfluidics for the separation of cells differing in both shape and size, demonstrates the potential of advanced microfluidic systems in cell sorting.

Ventriculoperitoneal (VP) shunt obstruction, often caused by protein and fat accumulation at the ventricular catheter ports, impedes cerebrospinal fluid (CSF) outflow, increases intracranial pressure (ICP), and leads to hydrocephalus. Current treatments require invasive shunt removal, reimplantation, or retrograde flush cleansing. We present a next-generation VP shunt system that actively removes blockages via external actuation. Our system, called CLogging Elimination ActuatoR Silicone (CLEARS), integrates a soft, expandable silicone tube within the catheter lumen. This soft robotic insert, capable of 900% strain, can inflate to dislodge blockages and then deflate to restore flow. To test CLEARS, we developed an ex vivo model simulating CSF flow and obstruction using a rapidly acting clogging agent. ICP upstream of the catheter was monitored to evaluate performance. When obstructed with 3 g of the clogging agent, ICP rose to 30 cmH(_2)O. Upon CLEARS activation, the silicone insert expanded through catheter ports and successfully removed the clog, restoring baseline ICP ((sim)0 cmH(_2)O) within approximately 40 s. Without the system, obstruction persisted and pressure remained elevated. Visual documentation confirmed the mechanism of action. The CLEARS system offers a promising solution to VP shunt occlusion by enabling non-invasive mechanical declogging. Our model replicates shunt obstruction and CSF dynamics, providing a testbed for device evaluation. The expandable insert maintained catheter flow and reduced ICP to normal levels after obstruction, representing a potential shift in how hydrocephalus is treated.

Epidermal growth factor receptor (EGFR) mutation detection is now commonly used in the management of cancer patients, particularly those diagnosed with non-small cell lung cancer. Molecular beacon-based sensing is direct and rapid, but its sensitivity is low. Conversely, high-sensitivity detection methodologies based on amplification are robust and sensitive but are limited by relatively require long turnaround times. In this study, we utilized a size-resolved, molecular beacon-based strategy for the rapid detection of EGFR genomic alterations, specifically exon 19 deletions and L858R point mutation. This technology combines a concentration and separation module, which allows us to successfully demonstrate the detection of deletions and point mutations of EGFR in five minutes with a mutant allele sensitivity of 10%. The use of a dual-color detection insures fast detection with a reduced risk of false positives. This work represents a first step toward the fast and specific detection of genetic mutations to improve the management of patients with hard-to-treat tumors.

The urgent need for adenosine triphosphate (ATP) detection spans various fields, particularly in biology and medicine. Developing a simple, quick, label-free, and highly sensitive biosensor for ATP detection is crucial. In this study, we created a label-free biosensor using a field-effect device, specifically an electrolyte-insulator-semiconductor (EIS) sensor, which was functionalized with aptamer and graphene. We prepared a nanocomplex by combining graphene with bovine serum albumin (BSA) in PBS and subjecting it to ultrasonication. This Graphene/BSA mixture was then combined with 70% glutaraldehyde to form the Graphene/BSA/GA nanocomplex. The successful modification of the EIS biosensor surface with Graphene/BSA/GA and aptamer immobilization was confirmed using atomic force microscopy (AFM), which indicated successful molecule attachment through surface roughness. Electrochemical characterization revealed that the biosensor is sensitive to ATP concentrations ranging from 0.1 nM to 100 nM, with a detection limit as low as 0.32 nM. Statistical analysis demonstrated the biosensor’s high sensitivity and specificity for ATP. Furthermore, the biosensor maintained stable performance for ATP detection over a period of 5 days. This sensing approach effectively detected ATP with outstanding performance, showing significant potential for advancing label-free ATP detection technologies.

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The accurate selection of living from dead pathogenic cells is crucial as exemplified in the context of detecting Legionella bacteria, which can be present in various water facilities and pose a threat to public health by causing severe respiratory problems. Traditional methods for Legionella detection, such as cultivation, are time-consuming, taking several days to yield valid results. Additionally, widely used bioanalytical methods like PCR lack the ability to distinguish between living and dead cells, leading to the potential for false-positive results. While dielectrophoresis has been proposed as a promising method for separating living and dead cells, our study contrasts with existing literature, revealing that the separation process and parameter characterization are non-trivial. In response to this challenge, our work introduces a novel, systematic approach of automated video analysis capable of quantifying the dielectrophoretic response of cells. By assigning a response coefficient to the dielectrophoretic effect at different conditions, our method identifies a narrow window for successful cell selection of viable Legionella cells from the non-pathogenic species L. parisiensis utilizing a microfluidic flow cell with top–bottom electrodes. These findings serve as a crucial pre-step in Legionella sensing, demonstrating applicability in experiments focused on the most relevant pathogenic species, L. pneumophila. Moreover, our method can be transferred to other cell types for quantitative detection of the dielectrophoretic response and identify optimal separation parameters.

Screening the amount of DNA closely related to early diagnosis of diseases or decoding information in target DNA sequences for biological medicine, infectious identification, or forensic analysis are highly essential in our daily life. This review provides clear understanding of nanostructured sensors (i.e., functionalized electrode-based sensors and nanopores) working for electrochemical assessment of DNA, along with their recent advances and unaddressed issues. Crucial constituents for sensor functionalization, electrochemical techniques, and electrodes, used in functionalized electrode-based sensors are briefly introduced, followed by analysis of using this type of sensors for DNA determination and the comparison of performances such as dynamic ranges and detection limits with other similar works. Subsequently, nanopore sensors including porin-based and solid-state nanopores applied for DNA sequencing are the other interests of discussion in the review. Beyond the achievement of high-resolution DNA sequencing based on porins coupled with enzymatic components, commonly used methods to solid-state nanopore creation, practical use of solid-state nanopores in DNA analysis, and computational modeling for nucleobase pore-threading simulation are depicted in more detail. Finally, conclusions in relation to recent advances and future developments are described. This work offers a powerful guideline for electrochemical assessment of DNA using either functionalized electrode-based sensors or nanopores, enabling scientific groups to have an entire picture upon electrochemical nanodevices used for DNA characterization.

In this research, we created a paper-based electrochemical immunosensor for detecting Pasteurella multocida antigen (Pm-Ag). Bacteria were obtained from a buffalo nasal swab, and the antigen was prepared and then injected into rabbits to induce a highly specific antibody (Pm-Ab). We created a carbon-based paper electrode chip using a screen-printing method, followed by coating with zinc oxide-nanoflowers (ZnO-NFs). The coating improved the sensor’s sensitivity due to the fact that zinc oxide- nanoflowers has remarkable physiochemical properties which enable electron transfer. Characterization of nanomaterial was conducted using UV-Vis spectroscopy, scanning electron microscopy (SEM), and energy dispersive X-rays (EDX). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used in electrochemical characterization. The developed platform demonstrated effective detection of Pm-Ag across concentrations from 0.9 to 6.4 µg/mL, achieving a limit of detection (LOD) as low as 0.9 µg/mL. These findings support the potential application of our sensor for detecting animal pathogens in a cost-effective, straightforward, and highly sensitive manner using a paper-based electrode chip.

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Extracellular vesicles (EVs) are nanosized particles secreted by most cells for information transmission, which affects the microenvironment. EVs are known to follow the characteristics and conditions of their mother cells and have attracted considerable attention for disease diagnosis and therapeutic effects. In particular, mesenchymal stem cell (MSC)-derived EVs have shown potential for facilitating regenerative wound healing, modulating immune responses, and inhibiting inflammatory diseases. However, previous isolation methods demonstrated limited EV yield, purity, and filter capacity. Here, we report a two-step tangential flow filtration (TFF) system using track-etched membranes with uniform cylindrical nanopores for effectively isolating EVs with high purity and yield. Using two different uniform nanoporous track-etched membranes (50 and 200 nm), only the particles in the small EV (sEV) size range were separated through a size-exclusion mechanism. Comparative analysis with the existing ultrafiltration membrane-based TFF system revealed that the nanoporous membrane-based TFF (Nano-TFF) system exhibited a separation efficiency (yield) exceeding twofold, achieving sEVs purity surpassing 90%. The efficacy of the highly purified sEVs was validated by incorporating them into wound dressing material and applying them to a wound animal model. Notably, the sEVs-loaded wound dressing group demonstrated enhanced wound recovery compared to control groups. The Nano-TFF system, which provides precise separation and high efficiency, can be applied to separate various bioactive agents, including sEVs, that require high-purity isolation.

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