Biomedical Microdevices最新文献

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.

Microfluidic chips often face challenges related to the formation and accumulation of air bubbles, which can hinder their performance. This study investigated a bubble trapping mechanism integrated into microfluidic chip to address this issue. Microfluidic chip design includes a high shear stress section of fluid flow that can generate up to 2.7 Pa and two strategically placed bubble traps. Commercially available magnets are used for fabrication, effectively reducing production costs. The trapping efficiency is assessed through video recordings with a phone camera and analysis of captured air volumes by injecting dye at flow rates of 50, 100, and 150 µL/min. This assessment uses L*A*B* color space with analysis of the perceptual color difference ∆E and computational fluid dynamics (CFD) simulations. The results demonstrate successful application of the bubble trap mechanism for lab-on-chip bubble detection, effectively preventing bubbles from entering microchannels and mitigating potential damage. Furthermore, the correlation between the L*A*B* color space and volume fraction from CFD simulations allows accurate assessment of trap performance. Therefore, this observation leads to the hypothesis that ∆E could be used to estimate the air volume inside the bubble trap. Future research will validate the bubble trap performance in cell cultures and develop efficient methods for long-term air bubble removal.

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Wearable and implantable biosensors have rapidly entered the fields of health and biomedicine to diagnose diseases and physiological monitoring. The use of wired medical devices causes surgical complications, which can occur when wires break, become infected, generate electrical noise, and are incompatible with implantable applications. In contrast, wireless power transfer is ideal for biosensing applications since it does not necessitate direct connections between measurement tools and sensing systems, enabling remote use of the biosensors. In addition, wireless sensors eliminate the need for a battery or energy harvester, reducing the size of the sensor. As far as we are aware, this is the first report ever describing a new method for wireless readout of a label-free electronic biosensor for detecting protein biomarkers. Our results reveal that we are able to successfully detect target protein and corresponding antibodies within this wireless setup. We are able to distinguish target protein in purified samples from a blank PBS sample as a negative control by tracking gradual changes in impedance at the input of the transmitter (P-value = 0.00788). We also demonstrate real-time wireless quantification of cytokines within rheumatoid arthritis patient serum samples (P-value = 0.00891). A Fine Gaussian Support Vector Machine is also used to differentiate protein from negative controls with the highest accuracy from a dataset of 54 experiments.

Intravenous drug administration delivers medication directly into the bloodstream, providing rapid and controlled effects, making it highly beneficial for emergencies or when immediate drug action is required. However, several risks are associated with intravenous drug administration, including infiltration and extravasation, which can lead to serious complications due to the rapid absorption of medication to the surrounding tissues. To prevent complications, here we proposed a non-contact sensor module to rapidly detect such events. The system does not interfere with the human skin, nor contaminating the flowing medication since only biocompatible materials are exposed to the liquid. The proposed sensor module was assembled as a flow channel with flow rate and pressure sensing functions. The flow rate sensing was realized using a micromachined thermal flow sensor fabricated on a thin polyimide film, while the pressure sensing was realized using a diaphragm structure and a MEMS pressure sensor. Basic characteristics of each function was evaluated and a proof of concept experiment demonstrated a rapid detection of infiltration/extravasation within a few s. Measurement of leaked fluid volume during the event was also demonstrated.

The broad availability of smartphones has provided new opportunities to develop less expensive, portable, and integrated point-of-care (POC) platforms. Here, a platform that consists of three main components is introduced: a portable housing, a centrifugal microfluidic disc, and a mobile phone. The mobile phone supplies the electrical power and serves as an analysing system. The low-cost housing made from cardboard serves as a platform to conduct tests. The electrical energy stored in mobile phones was demonstrated to be adequate for spinning a centrifugal disc up to 3000 revolutions per minute (RPM), a rotation speed suitable for majority of centrifugal microfluidics-based assays. For controlling the rotational speed, a combination of magnetic and acoustic tachometry using embedded sensors of the mobile phone was used. Experimentally, the smartphone-based tachometry was proven to be comparable with a standard laser-based tachometer. As a proof of concept, two applications were demonstrated using the portable platform: a colorimetric sandwich immunoassay to detect interleukin-2 (IL-2) having a limit of detection (LOD) of 65.17 ng/mL and a fully automated measurement of hematocrit level integrating blood-plasma separation, imaging, and image analysis that takes less than 5 mins to complete. The low-cost platform weighing less than 150 g and operated by a mobile phone has the potential to meet the REASSURED criteria for advanced diagnostics in resource limited settings.