Ultrasensitive Quantitative Migration Sensor for Monitoring the Quantitative Viscosity–Cell Migration Relationship

The relationship between extracellular viscosity and the cells' migration is a new and crucial clue indicating tumor growth and metastasis. However, their quantitative relationship has not yet been revealed. In this study, an ultrasensitive quantitative migration sensor (UQMS) that can quantitatively monitor the abnormal change of viscosities and the cell migration rate under abnormal extracellular viscosities with a record-breaking detection limit of 3 cells is developed for the first time. In this UQMS, a robust glucose/O₂ fuel cell (GFC) that can work steadily in body fluids and can output a continuous electrical signal serves as the energy driver and signal generator. At the anode of the GFC, we design a cell growth area two millimeters away from the electroactive area to ensure that the electroactive area is initially free from cell interference. The raised extracellular viscosity impedes mass transfer, leading to an instantaneous and linear decrease in the current output of the GFC. With the time going, the cancer cells migrate to the electroactive area on the anode, which further blocks the electron and mass transfer, leading to a time- and cell-number-dependent decrease in the current output of the GFC. By analyzing changes of the GFC's current output during different timeframes, the UQMS can quantitatively detect the extracellular viscosity in a wide range (1 cP-27 cP) that could distinguish the normal and abnormal viscosity; moreover, the quantitative relationship between long-term adherent cell migration and viscosities can be built at a level as low as 3 cells. Both of the migrations of adherent cells (ATCs) and circulating tumor cells (CTCs) under different viscosities can be quantitatively monitored by this UQMS. And we observe that the high viscosity enables the ATC to deform to migrate rapidly in an energy-efficient mode but slows down CTC migration; what is more, the migration of CTCs is significantly faster than that of ATCs. This work is expected to be highly helpful in assessing the risk of tumor metastasis from the migration of both ATCs and CTCs.