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Yang, et al.
be in different shape, for example, film, cantilever, or the electrical voltage or electrical resistance would
micropillars. The contraction force of CMs would bend be changed. In other words, the contraction force is
the elastic component, and the deformation is observed transferred to the electrical signal by the microsensors .
[67]
and recorded by a microscope. Then, the contraction Sun et al. developed a deformable PDMS membrane
force can be calculated by image processing. Parker et al. with CNT (a piezoresistive material) embedded inside.
fabricated the PDMS films in a heart-on-a-chip, and they They cultured hiPSC-CMs on the membrane. After a
cultured cells on these films which are referred to as period of incubation, the cell begun to contract and the
muscular thin films (MTFs) . The deformation caused contraction force causes the change of electrical resistance
[59]
by the contraction force can be read out by the optical of CNT (Figure 3Ci). This platform can continuously
signal. Using this platform, they studied the influence of measure the contraction force and beating rate of CMs
temperature and electrical stimulation on the contraction in a long term (14 days) . Another choice is to use
[68]
force (Figure 3Ai). Some researchers used micropillars the piezoelectric material to measure the contraction
to measure the contraction force. Cells cultured on the force [69-71] . When the contraction force triggered the
micropillars tend to adhere to the tips . When the cell deformation, an electrical voltage (and thus a measurable
[60]
contracts, it would deflect the surrounding micropillars current) is generated in the piezoelectric material. No
(Figure 3Aii) . The micropillars can be fabricated by soft external voltage is required for using this method.
[61]
lithography or other methods. Another similar structure The limitation of the piezoelectric and piezoresistive
that can measure contraction force is the biowires [62,63] . microsensors is that they have low sensitivity [69,72] . Crack-
[73]
In this method, the microtissues tend to enlace the two based microsensors may overcome this limitation .
wires and the contraction force drags them to each other Under the same contraction force, the sensitivity of
(Figure 3Aiii). Bashir et al. fabricated microcantilevers crack-based microsensor is 900 times higher than that
using 3D bioprinting with cross-linkable hydrogels. of piezoresistive microsensor. Lee et al. fabricated an
The cantilevers have similar mechanical properties with integrated high-sensitivity crack microsensor within a
native myocardial tissues and can be used to measure PDMS cantilever. The contraction force of CMs leads
the contraction force. Using this device, they studied the to the deformation of cantilever and further causes the
[74]
influence of substrate stiffness on the contraction force . distance change in the crack . When used in heart-on-a-
[64]
Chen et al. fabricated similar microsensors by 3D chip, the crack-based microsensors have high sensitivity
bioprinting. They obtained microcantilevers with CMs- and accuracy (Figure 3Cii).
laden GelMA hydrogel and measured the contraction For the aforementioned microsensors in heart-on-a-
force . chip, the fabrication is still challenging. 3D bioprinting
[28]
Another method to measure the contraction force is a powerful technique and can be used to fabricate the
is to use the structure coloration. Zhao et al. fabricated microsensors. Lewis et al. developed a multi-materials
a heart-on-a-chip with thin films which was made of 3D bioprinting platform to fabricate the heart-on-a-
[12]
the material inverse opal structure GelMA hydrogel . chip . They prepared six functional bioinks, including
[65]
The material would change its color when subjected to polyurethane (TPU), carbon black (CB), PDMS, and
external force. In this manner, the thin films performed dextran, to print the chips. In this heart-on-a-chip, they
as microsensors and the contraction of myocardial cells integrated a flexible microsensor which performed well
would cause a visible color change (Figure 3Bi). Such in monitoring the contraction of CMs. To fabricate the
microsensors can be used to characterize the beating microsensors by 3D bioprinting, choosing the conductive
frequency of CMs. Zhao et al. also fabricated a micro- material is a key task. Recently, a conductive polymer,
robot which was powered by the CMs. The materials of poly(3,4-ethylenedioxythiophene): polystyrene sulfonate
[42]
micro-robot include CNT and the inverse opal structure (PEDOT: PSS), has attracted considerable attention .
GelMA hydrogel (structure color material) . The micro- This material has shown excellent printability, high
[66]
robot can mimic the crawling behavior of a caterpillar conductivity, high resolution (~30 µm), and good
(Figure 3Bii). The crawling speed and structural color biocompatibility. This material is a promising candidate
are the indicators of myocardial tissues status. to fabricate the microsensors in heart-on-a-chip.
The above-mentioned methods are referred to
as direct methods. The contraction force-induced (2) Measurement of electrophysiological signals
deformation is usually observed under a microscope, Electrophysiological signal is another important indicator
making it inconvenient to some extent since the heart- of CMs. Some researchers fabricated microsensors in
on-a-chip is usually laid in the incubator for culture. An heart-on-a-chip to detect the electrical activity of CMs. The
alternative is to embed piezoelectric or piezoresistive planar MEA made of metal electrodes (gold or platinum)
materials into the microsensors. When the contraction is a conventional tool to monitor the electrophysiology
force causes the deformation in the elastic component, of CMs. Besides metal, some other conductive materials

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