Force sensing is one of the key challenges in realizing mechanical characterizations of living samples. Since living samples are normally cultured within a medium and tend to have nonlinearity in terms of their strain–stress curve, the two important features; a wide measurement range and being waterproof are required for the force sensor. Given these key requirements, in this paper, we present a force sensor probe that uses a quartz crystal resonator (QCR) to achieve the mechanical characterization of a HepG2 spheroid. The force sensor probe was fabricated using five-layered structure of quartz wafers; here, the layers are packaged using atomic diffusion bonding. We evaluated the performance of the fabricated force sensor probe, with results showing that the sensor had a wide measurement range of 1.8 × 106 from 0.19 μN to 340 mN. By using a constructed mechanical characterization system integrated with the QCR force sensor probe, we evaluated the stiffness of HepG2 spheroids over different culture periods. To evaluate the stiffness as a mechanical characteristics of HepG2 spheroid, we introduced an index SISlope. The results of mechanical characterization indicated that the measured SISlope changed along with each culture day. From these results, we succeeded in measuring mechanical characteristics of spheroids using our fabricated force sensor probe.
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