Biomedical Microdevices最新文献

To our best knowledge, there are no non-invasive and painless means for the diagnosis and treatment of intestinal bleeding as of now, especially the segment of intestine that cannot be reached by endoscopy. We proposed an intelligent intestinal bleeding diagnosis and treatment capsule (IBDTC) system for the first time to diagnose and treat intestinal bleeding with low power consumption, estimated to be about 2.16mW. A hue-saturation-light (HSL) color space method was applied to diagnose bleeding according to H (hue) values of the film dyed by blood. A MEMS-based micro-igniter works as the critical component of the micro-thruster that houses the propellant (74.6% potassium nitrate, 11.9% sulfur, 13.5% charcoal) and the detonating agent (dinitrodiazophenol), to help release drug. Bleeding detection and ignition tests were performed to justify its feasibility and reliability. Results demonstrated that the bleeding diagnosis module of the IBDTC can effectively detect bleeding and the micro-igniter can successfully ignite the propellant. Owing to its simplicity and intelligence, the IBDTC system will pave a way for future accurate treatment of small intestinal bleeding with no injury, no pain, no complicated supporting equipment, no need for in vitro operation and positioning.

This paper reports on the study of a piezoelectric actuated micropump with integrated elastomeric check valves that can transport small amounts of fluid in a highly controllable manner. The proposed micropump consists of a piezoelectric actuated fluid chamber with two integrated elastomeric check valves for regulating input and output flow direction, while restricting backflows. The actuation, fluid dynamic response and fluid–structure interactions at various working cycles are studied through a fully coupled multiphysics simulation (solid mechanics, electrostatic and fluid flow). The pump bodies are manufactured by micromachining of PMMA sheets, while the middle elastomeric membrane and diaphragm are fabricated by spin-coating PDMS. The experimental results confirm that the micropump can provide sufficiently low-velocity outflow for biomedical applications between 3.4 – 41.8 µl/min. The performance of the micropump is improved significantly through a convenient geometric modification of an off-the-shelf piezoelectric brass disc. Furthermore, the combination of this micropump with the 3D cell-culture microfluidic chip realizes the dynamic culture of cells encapsulated in 3D hydrogels with a continuous flowing medium, which offers the potential for changing the traditional mode of 3D cell culture with a static supply of nutrition and factors.

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Cancer is a prevalent cause of mortality globally, where early diagnosis leads to a reduced death rate. Many researchers' common strategies are based on personalized diagnostic methods with rapid response and high accuracy. This technology was developed by applying liquid biopsy instead of tissue biopsies in the case of tumor cell analysis that facilitates point-of-care testing for cancer diagnosis and treatment. In recent years, significant progress in microfluidic technology led to the successful isolation, analysis, and monitoring of cancer biomarkers in body liquid biopsy with merits like high sensitivity and flexibility, low sample usage, cost effective, and the ability of automation. The most critical and informative markers in body liquid refer to circulating tumor cells (CTCs) and extracellular vesicles derived from tumors (EVs) that carry various biomarkers in their structure (DNAs, proteins, and RNAs) as compared to ctDNA. The released ctDNA has a low half-life and decreased sensitivity due to large amounts of nucleic acid in serum. This review intends to highlight different cancer screening tests with a particular focus on the details regarding the only FDA-approved and awaiting technologies for FDA clearance to isolate CTCs and EVs based on microfluidics systems.

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Multiple myeloma (MM) is a bone marrow cancer of resident plasma cells that affects 125,000 patients in the U.S. with about 30,000 new cases per year. Its signature is the clonal proliferation of a single plasma cell that secretes a patient specific monoclonal immunoglobulin (M-Ig). Targeting the M-Ig in patient serum could allow sensitive and noninvasive identification of minimal residual disease in multiple myeloma. Aptamers, which are single-stranded oligonucleotides with affinity and specificity to a target molecule, have recently been introduced as affinity reagents for recognition of MM M-Igs. Here we exploit microfluidic SELEX technology to enable rapid and efficient generation of aptamers against M-Ig proteins from MM patients. We first characterize the technology by isolating aptamers with affinity towards the monoclonal antibody rituximab as a model M-Ig and then apply the technology to isolating aptamers specifically targeting M-Igs obtained from serum samples of MM patients. We demonstrate that high-affinity DNA aptamers (K_D < 50 nM) for M-Ig proteins from a patient sample could be isolated via microfluidic SELEX within approximately 12 h and using less than 100 micrograms of patient M-Ig. Such aptamers can potentially be used in personalized monitoring of minimal residual disease in MM patients.

Extracorporeal life support is an advanced therapy that circulates blood through an extracorporeal oxygenator, performing gas exchange outside the body. However, its use is limited by severe complications, including bleeding, clotting, and hemolysis. Semiconductor silicon-based membranes have emerged as an alternative to traditional hollow-fiber semipermeable membranes. These membranes offer excellent gas exchange efficiency and the potential to increase hemocompatibility by improving flow dynamics. In this work, we evaluate two next-generation silicon membrane designs, which are intended to be mechanically robust and efficient in gas exchange, while simultaneously reducing fabrication complexity. The “window” design features 10 µm pores on one side and large windows on the back side. The “cavern” design also uses 10 µm pores but contains a network of interconnected buried caverns to distribute the sweep gas from smaller inlet holes. Both designs were shown to be technically viable and able to be reproducibly fabricated. In addition, they both were mechanically robust and withstood 30 psi of transmembrane pressure without breakage or bubbling. At low sweep gas pressures, gas transfer efficiency was similar, with the partial pressure of oxygen in water increasing by 10.7 ± 2.3 mmHg (mean ± standard deviation) and 13.6 ± 1.9 mmHg for the window and cavern membranes, respectively. Gas transfer efficiency was also similar at higher pressures. At 10 psi, oxygen tension increased by 16.8 ± 5.7 mmHg (window) and 18.9 ± 1.3 mmHg (cavern). We conclude that silicon membranes featuring a 10 µm pore size can simplify the fabrication process and improve mechanical robustness while maintaining excellent efficiency.

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The construction of highly sensitive and specific immunosensing nanolabels have attracted tremendous attention in the development of reliable point-of-care disease diagnostics. However, there are still challenges with traditional immunoassays, such as complicated and time-consuming procedure, the use of enzyme label, non-specificity, and require readers for detection. Therefore, we have designed and developed site-directed antibody-immobilized calix[4]arene-gold nanoconjugate based colorimetric immunosensing nanolabel to offer high sensitivity. The prepared nanolabel enabled oriented binding of the antibodies by providing full accessibility of Fab domain for antigen binding. The improved sensitivity of the developed nanolabel was evaluated using vertical flow immunoassay (VFIA) for detecting C-reactive protein (CRP) with a lower detection limit up to 1 ng/ml. Our developed nanolabel was found to be highly specific, easy, quick, and appropriate for onsite detection. The nanolabel is validated with spiked blood samples which exhibited ~90% recovery having a relative error of ~2%. Furthermore, the nanolabel was also used for screening of human blood real samples which showed relative error of ~0.6%. The developed nanolabel can be utilized as a potential nanolabel for the quantitative detection of various biomolecules in clinical samples.

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Lung cancer is the leading cause of cancer death in the United States. It has the lowest 5-year survival rate among the most common cancers and therefore, early diagnosis is critical to improve the survival rate. In this paper, a new handheld electronic device is proposed to detect nine lung cancer biomarkers in the exhaled breath. An electrochemical gas sensor was produced through deposition of a thin layer of graphene and Prussian blue on a chromium-modified silicon substrate. Selective binding of the analyte was formed by molecular imprinting polymer (MIP). Subsequent polymerization and removal of the analyte yielded a layer of a conductive polymer on top of the sensor containing molecularly imprinted cavities selective for the target molecule. The sensors were tested over 1–20 parts per trillion (ppt) level of concentration while the sensor resistance has been monitored as the sensors react to the analyte by resistance change. Pentane sensor was also tested for selectivity. A printed circuit board was designed to measure the resistance of each sensor and send the data to a developed application in smartphone through Bluetooth. This handheld device has the potential to be used as a diagnostic method in the near future.

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Core–shell microparticles containing an aqueous core have demonstrated their value for microencapsulation and drug delivery systems. The most important step in generating these uniquely structured microparticles is the formation of droplets and double emulsion. The droplet generator must meet the performance and reliability requirements, including accurate size control with tunability and monodispersity. Herein, we present a facile technique to generate surfactant-free core–shell droplets with an aqueous core in a microfluidic device. We demonstrate that the geometry of the core–shell droplets can be precisely adjusted by the flow rates of the droplet components. As the shell is polymerized after the formation of the core–shell droplets, the resulting solid microparticles ensure the encapsulation of the aqueous core and prevent undesired release. We then study experimentally and theoretically the behaviour of resultant microparticles under heating and compression. The microparticles demonstrate excellent stability under both thermal and mechanical loads. We show that the rupture force can be quantitatively predicted from the shell thickness relative to the outer shell radius. Experimental results and theoretical predictions confirm that the rupture force scales directly with the shell thickness.

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The measurement of bio-impedance spectra at ultra low frequencies (sub-Hz) is known to require a considerably long time with the classical frequency-sweep method or other narrow-band periodic excitation signals. In this work, an impedance measurement technique based on using wide-band chaotic signals is proposed and experimentally validated over the frequency range (10,mHz-1,Hz). The technique was tested in both potentiostatic and galvanostatic modes, first using commercial components and then using an enhanced Howland current pump designed and fabricated in a 65nm CMOS technology. The accuracy of the proposed technique was assessed on fruit samples compared to measurements conducted using a research-grade Biologic VSP-300 electro-chemical station.

An automated microfluidic system with functionalized beads has been developed for multiplexed TORCH detection at point-of-care testing. A concise microfluidic chip consisting of a one-dimensional beads array is developed to simultaneously detect TOX, RUB, CMV, HSV-I and HSV-II respectively with five functionalized beads. A compact liquid handling module has been developed to automate the sandwiched chemiluminescence immunoassay within the one-dimensional beads array of the microfluidic chip. A precise ram pump is adopted to not only add reagent into the microfluidic chip from outside, but also facilitate elaborate fluid control inside the microfluidic chip for improved performance. A large-size waste chamber with a liquid-absorbing sponge holds the waste reagent within the microfluidic chip to prevent backflow. The one-dimensional beads array is heated from double-sides at 37 ℃ for sensitive detection with reduced time. A sensitive CMOS camera is adopted to take chemiluminescence image from the one-dimensional beads array, and a custom processing algorithm is adopted to analyze the image. For each serum sample, five different infections can be simultaneously detected with the automated microfluidic system. Experimental results show that efficient, sensitive, and accurate multiplexed TORCH detection can be conveniently achieved with the integrated microfluidic system.