Overview of research on additive manufacturing of hydrogel-assisted lab-on-chip platforms for cell engineering applications in photodynamic therapy research.

Lab-on-chips supported by hydrogel matrices are excellent solutions for cell culture; thus, this literature review presents examples of scientific research in this area. Several works are presenting the properties of biocompatible hydrogels that mimic the cellular environment published recently. Hydrogels can also be treated as cell transporters or as a structural component of microfluidic devices. The rapidly growing scientific sector of hydrogel additive manufacturing is also described herein, with attention paid to the appropriate mechanical and biological properties of the inks used to extrude the material, specifically for biomedical purposes. The paper focuses on protocols employed for additive manufacturing, e.g., 3D printing parameters, calibration, ink preparation, crosslinking processes, etc. The authors also mention potential problems concerning manufacturing processes and offer example solutions. As the novel trend for hydrogels enriched with several biocompatible additives has recently risen, the article presents examples of the use of high-quality carbon nanotubes in hydrogel research enhancing biocompatibility, mechanical stability, and cell viability. Moving forward, the article points out the high applicability of the hydrogel-assisted microfluidic platforms used for cancer research, especially for photodynamic therapy (PDT). This innovative treatment strategy can be investigated directly on the chip, which was first proposed by Jedrych E. et al. in 2011. Summarizing, this literature review highlights recent developments in the additive manufacturing of microfluidic devices supported by hydrogels, toward reliable cell culture experiments with a view to PDT research. This paper gathers the current knowledge in these intriguing and fast-growing research paths.

Inertial microfluidic mixer for biological CubeSat missions.

Nanosatellites of CubeSat type due to, i.a., minimized costs of space missions, as well as the potential large application area, have become a significant part of the space economy sector recently. The opportunity to apply miniaturized microsystem (MEMS) tools in satellite space missions further accelerates both the space and the MEMS markets, which in the coming years are considered to become inseparable. As a response to the aforementioned perspectives, this paper presents a microfluidic mixer system for biological research to be conducted onboard CubeSat nanosatellites. As a high complexity of the space systems is not desired due to the need for failure-free and remotely controlled operation, the principal concept of the work was to design an entirely passive micromixer, based on lab-on-chip technologies. For the first time, the microfluidic mixer that uses inertial force generated by rocket engines during launch to the orbit is proposed to provide an appropriate mixing of liquid samples. Such a solution not only saves the space occupied by standard pumping systems, but also reduces the energy requirements, ultimately minimizing the number of battery modules and the whole CubeSat size. The structures of the microfluidic mixers were fabricated entirely out of biocompatible resins using MultiJet 3D printing technology. To verify the functionality of the passive mixing system, optical detection consisting of the array of blue LEDs and phototransistors was applied successfully. The performance of the device was tested utilizing an experimental rocket, as a part of the Spaceport America Cup 2023 competition.

3D Printed Hydrogel Sensor for Rapid Colorimetric Detection of Salivary pH.

Salivary pH is one of the crucial biomarkers used for non-invasive diagnosis of intraoral diseases, as well as general health conditions. However, standard pH sensors are usually too bulky, expensive, and impractical for routine use outside laboratory settings. Herein, a miniature hydrogel sensor, which enables quick and simple colorimetric detection of pH level, is shown. The sensor structure was manufactured from non-toxic hydrogel ink and patterned in the form of a matrix with 5 mm × 5 mm × 1 mm individual sensing pads using a 3D printing technique (bioplotting). The authors' ink composition, which contains sodium alginate, polyvinylpyrrolidone, and bromothymol blue indicator, enables repeatable and stable color response to different pH levels. The developed analysis software with an easy-to-use graphical user interface extracts the R(ed), G(reen), and B(lue) components of the color image of the hydrogel pads, and evaluates the pH value in a second. A calibration curve used for the analysis was obtained in a pH range of 3.5 to 9.0 using a laboratory pH meter as a reference. Validation of the sensor was performed on samples of artificial saliva for medical use and its mixtures with beverages of different pH values (lemon juice, coffee, black and green tea, bottled and tap water), and correct responses to acidic and alkaline solutions were observed. The matrix of square sensing pads used in this study provided multiple parallel responses for parametric tests, but the applied 3D printing method and ink composition enable easy adjustment of the shape of the sensing layer to other desired patterns and sizes. Additional mechanical tests of the hydrogel layers confirmed the relatively high quality and durability of the sensor structure. The solution presented here, comprising 3D printed hydrogel sensor pads, simple colorimetric detection, and graphical software for signal processing, opens the way to development of miniature and biocompatible diagnostic devices in the form of flexible, wearable, or intraoral sensors for prospective application in personalized medicine and point-of-care diagnosis.

Lab-on-chip technologies for space research - current trends and prospects.

The in-depth analysis concerning application of microfluidic instruments for space biology research is presented. The article focuses on recently investigated key scientific fields, i.e., lab-on-chips applied to the biomedical studies performed in the (1) International Space Station and (2) CubeSat nanosatellites. The paper presents also the lab-on-chip devices that were fabricated with a view to future space biology research and to those that to date have been solely been tested under Earth laboratory conditions and/or simulated microgravity environments. NASA and ESA conceptual mission plans for future are also mentioned, concerning for instance "tissue chips" and the ESA-SPHEROIDS campaign. The paper ends with final conclusions and future perspectives regarding lab-on-chip application in the space biology sector and its impact on novel biomedical and pharmaceutical strategies.

3D bio-printed hydrogel inks promoting lung cancer cell growth in a lab-on-chip culturing platform.

The results of a lab-on-chip (LOC) platform fabrication equipped with a hydrogel matrix is reported. A 3D printing technique was used to provide a hybrid, "sandwiched" type structure, including two microfluidic substrates of different origins. Special attention was paid to achieving uniformly bio-printed microfluidic hydrogel layers of a unique composition. Six different hydrogel inks were proposed containing sodium alginate, agar, chitosan, gelatin, methylcellulose, deionized water, or 0.9% NaCl, varying in proportions. All of them exhibited appropriate mechanical properties showing, e.g., the value of elasticity modulus as similar to that of biological tissues, such as skin. Utilizing our biocompatible, entirely 3D bio-printed structure, for the first time, a multi-drug-resistant lung cancer cell line (H69AR) was cultured on-chip. Biological validation of the device was performed qualitatively and quantitatively utilizing LIVE/DEAD assays and Presto blue staining. Although all bio-inks exhibited acceptable cell viability, the best results were obtained for the hydrogel composition including 3% sodium alginate + 7% gelatin + 90% NaCl (0.9%), reaching approximately 127.2% after 24 h and 105.4% after 48 h compared to the control group (100%). Further research in this area will focus on the microfluidic culture of the chosen cancer cell line (H69AR) and the development of novel drug delivery strategies towards appropriate in vivo models for chemotherapy and polychemotherapy treatment.