piRT-IFC: Physics-informed real-time impedance flow cytometry for the characterization of cellular intrinsic electrical properties

Real-time transformation was important for the practical implementation of impedance flow cytometry. The major obstacle was the time-consuming step of translating raw data to cellular intrinsic electrical properties (e.g., specific membrane capacitance C-sm and cytoplasm conductivity s(cyto)). Although optimization strategies such as neural network-aided strategies were recently reported to provide an impressive boost to the translation process, simultaneously achieving high speed, accuracy, and generalization capability is still challenging. To this end, we proposed a fast parallel physical fitting solver that could characterize single cells' C-sm and s(cyto) within 0.62 ms/cell without any data preacquisition or pretraining requirements. We achieved the 27000-fold acceleration without loss of accuracy compared with the traditional solver. Based on the solver, we implemented physics-informed real-time impedance flow cytometry (piRT-IFC), which was able to characterize up to 100,902 cells' C-sm and s(cyto) within 50 min in a real-time manner. Compared to the fully connected neural network (FCNN) predictor, the proposed real-time solver showed comparable processing speed but higher accuracy. Furthermore, we used a neutrophil degranulation cell model to represent tasks to test unfamiliar samples without data for pretraining. After being treated with cytochalasin B and N-Formyl-Met-Leu-Phe, HL-60 cells underwent dynamic degranulation processes, and we characterized cell's C-sm and s(cyto) using piRT-IFC. Compared to the results from our solver, accuracy loss was observed in the results predicted by the FCNN, revealing the advantages of high speed, accuracy, and generalizability of the proposed piRT-IFC.

Automated summary

Real-time transformation is crucial for impedance flow cytometry in practice, but the translation of raw data to cellular intrinsic electrical properties is time-consuming. We proposed a fast parallel physical fitting solver that characterizes single cells' electrical properties within 0.62 ms/cell. Based on this solver, we implemented physics-informed real-time impedance flow cytometry (piRT-IFC), which showed comparable speed but higher accuracy than the fully connected neural network predictor. In addition, we demonstrated the advantages of piRT-IFC in handling unfamiliar samples without pretraining.