Biomedical Microdevices最新文献

GPR120 is a free fatty acid receptor capable of signalling excess fatty acids. GPR120 can be activated by various types of free fatty acids, causing intracellular signal transduction and exerting energy regulation, immune homeostasis, and neuronal functions. It has been suggested that Trp198 may be an important residue in the recognition and activation of GPR120 by fatty acid ligands, but direct experimental evidence is lacking. In this study, a GPR120-based bilayer gold nanoparticle biosensor (Trp198→Pro) was constructed by genetically manipulating Trp198 on GPR120 by replacing it with proline for the determination of linkage variability between 14 naturally occurring fatty acid ligands and mutant receptors. The results showed that both before and after amino acid substitution the GPR120 bilayer nanogold receptor sensor responded to all 14 natural fatty acid ligands. And the linkage transformation constants of crotonic acid, dodecanoic acid, oleic acid, linoleic acid, α-linolenic acid, and DHA decreased after Trp198 was replaced by Pro. To further reveal its molecular recognition mechanism, molecular simulation docking experiments were performed on GPR120 and 14 fatty acid ligand compounds before and after amino acid substitutions, respectively. The results showed that before and after the amino acid substitutions, the binding conformational affinity values of GPR120 docked with the ligands were negative, implying that these fatty acid ligands can spontaneously bind to the active pocket of GPR120 without absorbing external energy. Upon replacement of Trp198 by Pro, the active pocket of GPR120 at the optimal docking site with the fatty acid ligand is altered, leading to changes in the amino acid residues that exert the interaction. The above results demonstrate that Trp198 indeed plays an important role in the recognition of fatty acid ligands on GPR120. The present study provides direct quantitative evidence for the roles played by different amino acid residues in receptor-ligand recognition and interaction. At the same time, it provides new ideas for the study of other receptor-ligand-linked metastable mechanisms and kinetic laws.

Microfluidic chips have emerged as versatile and powerful tools that enable the precise manipulation of fluids and bioparticles at the microscale. Their impact on detection applications is profound, offering advantages such as miniaturization, enhanced sensitivity, multiplexing capability, and integrated functions. These chips can be customized for specific techniques, such as DNA analysis, immunoassays, chemical sensing, and cell-based assays. With a wide range of types available, including Lab-on-a-Chip, droplet-based, paper-based, electrochemical, optical, and magnetic chips, they find applications in diverse fields such as medical diagnostics, DNA analysis, cell analysis, food safety testing, environmental monitoring, and industrial processes. This powerful technology replicates laboratory capabilities on miniature chip-scale devices, resulting in time and cost savings while enabling portability and field-use capability. Its impact spans genetic analysis, proteomic analysis, cell culture, biosensors, pathogen detection, and point-of-care diagnostics, playing a pivotal role in advancing chemical and biological analysis. The overall aim of this review is to provide an overview of the development of microfluidic biochips for biological detection and discuss their various applications.

Flexible, microneedle-based electrodes offer an innovative solution for high-quality physiological signal monitoring, reducing the need for complex algorithms and hardware, thus streamlining health assessments, and enabling earlier disease detection. These electrodes are particularly promising for improving patient outcomes by providing more accurate, reliable, and long-term electrophysiological data, but their clinical adoption is hindered by the limited availability of large-scale population testing. This review examines the key advantages of flexible microneedle electrodes, including their ability to conform to the skin, enhance skin-electrode contact, reduce discomfort, and deliver superior signal fidelity. The mechanical and electrical properties of these electrodes are thoroughly explored, focusing on critical aspects like fracture force, skin penetration efficiency, and impedance measurements. Their applications in capturing electrophysiological signals such as ECG, EMG, and EEG are also highlighted, demonstrating their potential in clinical scenarios. Finally, the review outlines future research directions, emphasizing the importance of further studies to enhance the clinical and consumer use of flexible microneedle electrodes in medical diagnostics.

Liver zonation is a fundamental characteristic of hepatocyte spatial heterogeneity, which is challenging to recapitulate in traditional cell cultures. This study presents a novel microfluidic device designed to induce zonation in liver cell cultures by establishing an oxygen gradient using standard laboratory gases. The device consists of two layers; a bottom layer containing a gas channel network that delivers high (cell incubator air, 19% oxygen) and low oxygenated (nitrogen) gases to create three distinct zones within the cell culture chamber in the layer above. Computational simulations and ratiometric oxygen sensing were employed to validate the oxygen gradient, demonstrating that stable oxygen levels were achieved within two hours. Liver zonation was confirmed using immunofluorescence staining, which showed zonated albumin production in HepG2 cells directly correlating with oxygen levels and mimicking in-vivo zonation behavior. This user-friendly device supports studies on liver zonation and related metabolic disease mechanisms in vitro. It can also be utilized for experiments that necessitate precise gas concentration gradients, such as hypoxia-related research areas focused on angiogenesis and cancer development.

Retinal prosthesis has been one of the medical strategies aimed at restoring some degree of vision for patients affected by retinal degenerative diseases, such as Retinitis Pigmentosa (RP) and age-related macular degeneration (AMD), which are leading causes of irreversible visual loss. In retinal prosthesis, electrical pulses are typically delivered to the retinal neurons via electrodes on the surface of the implant. In this work, we fabricated 3D carbon pillar electrodes by pyrolysis of SU-8 structures defined photolithographically on Si wafers. We then measured compound action potentials induced in porcine neuroretinas stimulated with electrical pulses. The recorded spikes were validated to be biological in origin by adding the voltage-gated sodium-channel blocking agent tetrodotoxin. The minimum threshold voltage needed to effectively stimulate retinal cells, such as retinal ganglion cells, with 3D electrodes was analyzed through systematic investigation of the spike rate and amplitudes as a function of stimulation voltage. 3D electrodes significantly increased spike rate and amplitudes above spontaneous activity in the tissue during stimulation and outperformed the 2D counterpart, both in terms of spike rate and amplitude. Our results indicate a threshold voltage range of 500-600 mV for 1 ms pulses at a frequency of 10 Hz above which a significant increase in spike count was observed. Furthermore, we report an order of magnitude increase in peak-to-peak amplitude for evoked spikes (> 3 mV), compared to spontaneous spikes (∼ 200 µV). Based on numerical integration, we estimate the area under the curve to be ~14 times larger in evoked compound action potentials compared to spontaneous activity. This indicates the relative increase in number of contributing cells to the compound action potential. At a stimulation voltage of 600 mV the spike rate for 3D electrodes was above 10 spikes/channel/s. We hypothesize that the significant difference between 2D and 3D electrodes is not only caused by the higher active electrode surface area of the 3D micropillar electrodes, but also by more intricate contact and interaction with the inner cell layers of the retinal tissue. Our findings indicate that 3D carbon micropillar electrodes are promising for electrical stimulation of the retina.

The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) protein is specifically related to tumor cell proliferation in breast cancers. Its presence in biological serum samples indicates presence or progression of cancer, becoming a promise biomarker. However, their detection needs a simple and high accuracy platform. In this study, we report the develop and optimization of a simple highly sensitive electrochemical platform for HER2. Gold electrode surface was modified with a self-assembled monolayer composed by DNA aptamer, 6-(ferrocenyl) hexanethiol and 6-mercapto-1-hexanethiol. Electrochemical impedance spectroscopy was used to quantify the changes in capacitance on the interface due to the presence ferrocene, whether acting as a redox charge or its behavior under different HER2 concentration in PBS and undiluted human serum. As a result, the approach allows detection of HER2 with a limit of detection of 3.61 pg/mL, 12.28 nF sensitivity per decade and a linear range from 1 pM to 1 (:mu:)M in serum. This electrochemical aptasensor can be applied to different arrays for aptamer screening and has a significant importance to interaction study of biological systems.

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Recently, photodynamic therapy (PDT) which involves a photosensitizer (PS), a special drug activated by light, and light irradiation has been widely used in treating various skin diseases such as port-wine stain as well as cancers such as melanoma and non-melanoma skin cancers. PDT comprises two general steps: the introduction of PS into the body or a specific spot to be treated, and the irradiation process using a light source with a specific wavelength to excite the PS. Although PDT is gaining great attention owing to its potential as a targeted approach in the treatment of skin cancers, several limitations still exist for practical use. One of the biggest challenges is the limited penetration of light owing to scattering, reflection, and absorption of light inside the skin layers. In addition, accidental light exposure of the target area causes additional cellular damage, which causes unexpected complications. To solve these issues, we introduced an optical microneedle–lens array (OMLA) to improve the efficiency and safety of PDT treatment. We designed and fabricated a novel optical microneedle–lens array with controlled dimensions to optimize light transmission. In addition, PS was coated uniformly over the tips of the OMLA using the dip coating method. Finally, we confirmed that the PS coated on the OMLA was released into the target area and subsequently generated radical oxygen by light irradiation. We expect that our proposed OMLA for PDT treatment can realize a new light-transmission platform optimized for PDT with targeting various types of skin cancers.

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Globally, breast cancer is the most frequent type of cancer, and its early diagnosis and screening can significantly improve the probability of survival and quality of life of those affected. Liquid biopsy-based targets such as circulating tumor cells, circulating tumor DNA, and exosomes have been instrumental in the early discovery of cancer, and have been found to be effective in stage therapy, recurrence monitoring, and drug selection. Biosensors based on these target related biomarkers convert the tested substances into quantifiable signals such as electrical and optical signals through signal transduction, which has the advantages of high sensitivity, simple operation, and low invasiveness. This review provides an overview of the latest progress of liquid biopsy biomarkers in the diagnosis, prognosis and treatment of breast cancer, compares the application and advantages of different biosensors based on these biomarkers in the diagnosis of breast cancer, and analyzes the limitations and solutions of biosensor based methods.