Nonmediated, Label-Free Based Detection of Cardiovascular Biomarker in a Biological Sample.

Direct electrochemical (EC) monitoring in a cell culture medium without electron transporter as called mediator is attractive topic in vitro organoid based on chip with frequently and long-time monitoring since it can avoid to its disadvantage as stability, toxicity. Here, direct monitoring with nonmediator is demonstrated based on impedance spectroscopy under the culture medium in order to overcome the limitation of mediator. The applicability of EC monitoring is shown by detecting alpha-1-anti trypsin (A1AT) which is known as biomarkers for cardiac damage and is widely chosen in organoid cardiac cell-based chip. The validity of presented EC monitoring is proved by observing signal processing and transduction in medium, mediator, medium-mediator complex. After the observation of electron behavior, A1AT as target analyte is immobilized on the electrode and detected using antibody-antigen interaction. As a result, the result indicates limit of detection is 10 ng mL-1 and linearity for the 10-1000 ng mL-1 range, with a sensitivity of 3980 nF (log [g mL])-1 retaining specificity. This EC monitoring is based on label-free and reagentless detection, will pave the way to use for continuous and simple monitoring of in vitro organoid platform.

Label-Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes.

Development of an efficient sensing platform capable of continual monitoring of biomarkers is needed to assess the functionality of the in vitro organoids and to evaluate their biological responses toward pharmaceutical compounds or chemical species over extended periods of time. Here, a novel label-free microfluidic electrochemical (EC) biosensor with a unique built-in on-chip regeneration capability for continual measurement of cell-secreted soluble biomarkers from an organoid culture in a fully automated manner without attenuating the sensor sensitivity is reported. The microfluidic EC biosensors are integrated with a human liver-on-a-chip platform for continual monitoring of the metabolic activity of the organoids by measuring the levels of secreted biomarkers for up to 7 d, where the metabolic activity of the organoids is altered by a systemically applied drug. The variations in the biomarker levels are successfully measured by the microfluidic regenerative EC biosensors and agree well with cellular viability and enzyme-linked immunosorbent assay analyses, validating the accuracy of the unique sensing platform. It is believed that this versatile and robust microfluidic EC biosensor that is capable of automated and continual detection of soluble biomarkers will find widespread use for long-term monitoring of human organoids during drug toxicity studies or efficacy assessments of in vitro platforms.

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors.

Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.

Simple fabrication method for a porous poly(vinyl alcohol) matrix by multisolvent mixtures for an air-exposed model of the lung epithelial system.

We introduce a simple and easy method for fabricating a thin and porous matrix that can be used as an extracellular matrix (ECM). A porous poly(vinyl alcohol) (PVA) matrix was created through recrystallization by multiple solvents under distilled water (DW), isopropyl alcohol (IPA), and a combination of DW and IPA. The crysatllization was driven by precipitating and dissolving a solute in a solution of a solvent and a nonsolvent, which induced the formation of microspheres in the IPA. The crystal structure depended on the ratio of the solvent/nonsolvent and the concentration of the PVA aqueous solution; these properties were used to tune the thickness, size, and porosity of the matrices. The resulting PVA matrix was chemically stabilized through a reaction with glutaraldehyde in the IPA solution. We demonstrated that a very thin and porous PVA matrix provided an effective functional model of the lung epithelial system. Lung epithelial cells (A549) displayed a high affinity for this matrix, which was permeable to the culture medium. These properties facilitated culturing under the air environment.

Microfluidic spinning of micro- and nano-scale fibers for tissue engineering.

Microfluidic technologies have recently been shown to hold significant potential as novel tools for producing micro- and nano-scale structures for a variety of applications in tissue engineering and cell biology. Over the last decade, microfluidic spinning has emerged as an advanced method for fabricating fibers with diverse shapes and sizes without the use of complicated devices or facilities. In this critical review, we describe the current development of microfluidic-based spinning techniques for producing micro- and nano-scale fibers based on different solidification methods, platforms, geometries, or biomaterials. We also highlight the emerging applications of fibers as bottom-up scaffolds such as cell encapsulation or guidance for use in tissue engineering research and clinical practice.

Micro/Nanometer-scale fiber with highly ordered structures by mimicking the spinning process of silkworm.

A new method for the microfluidic spinning of ultrathin fibers with highly ordered structures is proposed by mimicking the spinning mechanism of silkworms. The self-aggregation is driven by dipole-dipole attractions between polar polymers upon contact with a low-polarity solvent to form fibers with nanostrands. The induction of Kelvin-Helmholtz instabilities at the dehydrating interface between two miscible fluids generates multi-scale fibers in a single microchannel.

Biomimetic and molecular level-based silicate bioactive glass-gelatin hybrid implants for loading-bearing bone fixation and repair.

Biomedical implants for successful bone fixation and repair should be biodegradable, and of matched mechanical strength, bone-bonding bioactivity and good biocompatibility. However, current bone implants in the clinic and research are usually not meeting the demands of ideal implants. Here, at low temperatures, we develop a biomimetic molecular level-based silicate bioactive glass-gelatin bone implant with matched physicochemical and biological properties. Our implant could mimic the physical structure at the molecular and nanoscale levels, and presents a high compressive strength (beyond 120 MPa), suitable modulus (300-600 MPa) and strain percent (30%). In addition, the biomimetic implants also showed a linear biodegradation behavior which indicated their stable biodegradation ability. An in vitro simulated body fluid (SBF) test showed that a uniform biomineralization layer was formed on the implant under short times, which shows the good bone-bonding bioactivity of the implants. An in vitro marrow stem cells (MSC) culture showed that our biomimetic implants possessed good biocompatibility by enhancing cell proliferation. These results indicated that our biomimetic hybrid implants may be competitive candidates for bone fixation and repair biomaterials.

Microfluidic spinning of flat alginate fibers with grooves for cell-aligning scaffolds.

Alginate microribbons with longitudinally grooved microstructures are continuously fabricated by means of a microfluidic system. The number and dimensions of the microgroovesare successfully controlled by regulation of the slit-shaped channel (yellow in figure). This method opens up the possibility of mass production of scaffolds for tissue engineering purposes, as it is proved that the grooved flat fibers can be used to align other types of cells in culture.

Beta-lactam antibiotic sensitization and its relationship to allergic diseases in tertiary hospital nurses.

PURPOSE: Skin allergies through type 1 and 4 hypersensitivity reactions are the most frequent manifestations of drug allergies. We had previously experienced a case of a nurse with cefotiam-induced contact urticaria syndrome. To aid in preventing the progression of drug-induced allergic disease in nurses, we conducted a survey of tertiary hospital nurses who were likely to have been exposed professionally to antibiotics. METHODS: All 539 staff nurses at a tertiary hospital were asked to respond to a questionnaire regarding antibiotic exposure. Of the 457 nurses (84.8%) who responded, 427 (79.2%) received a physical examination of the hands and 318 (59.0%) received skin prick tests with the beta-lactam antibiotics cefotiam, cefoperazone, ceftizoxime, flomoxef, piperacillin and penicillin G. RESULTS: A positive response to at least one of the antibiotics occurred in 8 (2.6%) of the 311 subjects included in the analysis and stages 1 and 2 contact urticaria syndrome were observed in 38 (8.9%) and 3 (0.7%) of 427 nurses, respectively. The frequencies of a positive antibiotic skin test (6.9 versus 1.3%, chi(2)=7.15, P=0.018), stage 1 contact urticaria syndrome (14.4 versus 7.4%, chi(2)=4.33, P=0.038) and drug allergy (15.3 versus 3.6%, chi(2)=18.28, P=0.000) were higher in subjects with a positive skin allergy history than in those without. Allergic rhinitis (P=0.02, OR=3.86, CI=1.23-12.06), night cough (P=0.04, OR=3.12, CI=1.03-9.41) and food allergy (P=0.00, OR=9.90, CI=3.38-29.98) were significant risk factors for drug allergy. CONCLUSIONS: Antibiotic sensitization and drug allergy occurred more frequently in nurses with a positive skin allergy history. Atopy may be an important risk factor for drug allergy.

Oil droplet generation in PDMS microchannel using an amphiphilic continuous phase.

This paper reports an amphiphilic solution can be used as a new continuous phase to generate double droplet emulsions (water/oil/IPA) with neither surface treatment nor surfactant in PDMS microfluidic chip. The affinity of various amphiphilic solutions in the microchannel was influenced by the polarity ratio and the size of molecules. The polarity ratio of isopropyl alcohol (IPA) was closest to that of the recovered PDMS surface and the chain length of IPA was also suitable for high affinity. IPA showed the highest affinity for the recovered PDMS and was selected as the continuous phase to form oil droplets in a PDMS microchannel. With this new continuous phase solution, IPA, we could successfully generate not only oil droplets but also double emulsions in the PDMS microfluidic chips.