Figure 5. Organoid in three-dimensional self-rolled biosensor array. Source: 83. Reproduced with permission from Science Advances. (a) 3D-SR-BAs for electrical interrogation of human electrogenic spheroids. (b) Electrical recordings in 3D of cardiac spheroids.
4.2 Biological sensing
Microfluidics is a technology for precisely controlling and manipulating micro-scale fluids, especially sub-micron structures. It is also called Lab-on-a-Chip or microfluidic chip technology[84]. It integrates basic operation units such as sample preparation, reaction, separation, and detection in the biological, chemical, and medical analysis process on a micron-scale chip to automatically complete the entire analysis process. Due to its great potential in the fields of biology, chemistry, medicine, etc., it has developed into a new research field that intersects multiple disciplines such as biology, chemistry, medicine, fluids, electronics, materials, and machinery. At the same time, it also has the advantages of a lightweight, small amount of samples and reagents, low energy consumption, fast reaction speed, a large number of parallel processing, and ready-to-use disposables[85].
Suspended network technology has been fully utilized at present for the loading and cultivation of single-cell, multi-cell, and micro-tissue spheres. For example, Banerjee et al. used the hanging drop method to study the potential and cytotoxicity of stem cells to differentiate into specific lineages[86]. Another research used hanging-drop culture methods to distinguish the main erythroid progenitor cells derived from mouse tissue or human umbilical cord blood and compare with methylcellulose culture methods. The results proved that the behavior of isolated primary erythroid cells was comprehensively evaluated within the range of genetic and drug-induced disturbances[87]. For the application of embryonic bodies, the researchers used the differentiation of mouse embryonic stem cells (mESCs) to establish a model for evaluating embryotoxicity in vitro , and selected highly predictive protein markers specific to the developing heart tissue to enhance embryotoxicity, and then evaluated in vitro [88]. Multicellular tumorspheres (MCTS) are now widely used as organotypic models of normal and solid tumor tissues. Studies have used the hanging drop method to produce spheroids in the liver cancer cell line HepG2 breast adenocarcinoma cell line MCF-7, and it is a three-dimensional tissue-like structure that shows a high degree of the organization[89]. The use of 3D cell models in anticancer drug sensitivity testing is of great importance. The 384 hanging drop array plate has a high-throughput function and is used for cells with concentric layer patterning of different cell types and the cultivation of multiple cell types[90]. A compact on-chip pumping using the surface tension of the liquid-air interface for flow drive realized the real-time feedback control loop of the beating of heart organoids derived from human induced pluripotent stem cells[91]. This method provides a way to study the effects of compounds on the heart itself and the effects of fluid circulation changes on other organ models in the system. There was also a device that seamlessly combines an open microfluidic device with fluorescence-activated cell sorting (FACS), so that all cells, including stem cells, be directly sorted into the designated culture chamber in a fully automated manner and with high precision. Then, cells and microtissue culture were carried out in the form of hanging drops under controlled perfusion[92]. The potential for disease surveillance was also reported[93,94]. Furthermore, the corresponding inter-electrode impedance value could be calculated by reading the current generated by applying an AC voltage to evaluate the sample between the electrodes. Or through the chemical reaction to generate electrical current to monitor changes in material metabolism[94,95]. Meanwhile, the porous microfluidic platform is capable of multiplexing multiple drugs to a small biopsy tissue to evaluate the impact of drugs on its viability and microenvironment, thereby providing a testing platform for drug development and personalized medicine[96]. This method has been used for basic physiological research, metabolism, tumor biology, toxic alcohol, cell tissue, and bioartificial tissue development.
Therefore, it is speculated that the microfluidic hanging drop technology will also play a significant role in exploring the mechanism of taste loss or how to restore taste in patients with taste loss. Studies have shown that many regulatory factors play a role in the development of the taste system. Researchers have shown that artificial tongues sense smells more efficiently. This provides a reliable theoretical basis for the treatment of taste loss[9,97,98].
The increasing progress in vitro models, chips integrating multiple organs have been made in recent years, and it is a major step forward in organ-on-a-chip technology[99] (Figure 6a). Functional drug screening on a complete tumor sample of a specific patient is a promising method for determining the best therapy for each patient. The response of a patient’s cancerous tissue biopsy to a single drug (or drug combination) is highly dependent on the tumor microenvironment (TME), which includes a variety of resident and infiltrating host cells, secreted factors, and extracellular matrix proteins. Combining the microanatomy of tumor tissue with microfluidics can better protect the tissue microenvironment in the intact tissue for drug testing[100] (Figure 6b). Because the tissue is taken directly from the patient, it does not cause any major damage to the tumor microenvironment. This technology can capture a large amount of micro-tissue. However, such tumor spheres only retain a limited tumor microenvironment, which highlights the need for new high-throughput drug screening platforms. Therefore, the combination of microfluidic technology and organoids can accurately reproduce the interaction between drugs and tumors, which greatly promotes drug screening and disease treatment.