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.