Dynamic Liposome Sensing Platform to Wirelessly Ensure Nucleic Acid Encapsulation via Non-Contact Perception

The demand for a high-throughput and noncontact monitoring system to guarantee the payload of nucleic acid in liposomes is rapidly increasing for raising efficiency in gene therapeutics. Herein, inspired by electroreceptors of elasmobranch fishes, a dynamic liposome sensing (DLs) platform is developed by implementing the electret layer (CYTOP)-coated single-walled carbon nanotube-based thin film transistor (eSWCNT-TFT) which can monitor differences of the net-charge on deoxyribonucleic acid (DNA)-loaded liposomes. The SWCNT-TFTs are roll-to-roll (R2R) printed on plastic film and then, simply laminated by the droplet microfluidic chip to optimize the aqueous droplet lengths by controlling a ratio of injecting speed between oil to aqueous solution. The buffer solution, DNA-free liposomes, and DNA-loaded liposomes respectively induced different electrostatic potentials on eSWCNT-TFTs without direct contact with the electret layer, thereby shifting the threshold voltage (V_th). The DLs platform's integrated wireless communication module can monitor DNA-loaded liposome droplets with encapsulation efficiency of up to 87.3 ± 3.2% with a sensitivity of 18.61 nA ppm⁻¹ per single droplet at a flow rate of 1 µL min⁻¹. It can be scaled up by adding more microfluidic droplet channels on eSWCNT-TFT arrays, making it especially useful for in-situ checks of messenger ribonucleic acid (mRNA)-based vaccines just before bottling.