Enhanced Sensitivity of Cell Identification in Complex Environments Using Chirally Inverted L‐DNA‐Based Logic Devices

Accurate identification and isolation of target cells are crucial for precision diagnosis and treatment. DNA aptamer-based logic devices provide a distinct advantage in this context, as they can logically analyze multiple cell surface markers with high efficiency. However, the susceptibility of natural DNA (D-DNA) to degradation can compromise the sensitivity and specificity of these devices, potentially leading to false-positive and false-negative results, particularly in complex biological environments. To address this issue, dual- and triple-aptamer-based cell-surface logic devices are designed and developed using mirror-image L-DNA, a chiral molecule of D-DNA with high biostability. These devices allow for simultaneous analysis of multiple cell surface proteins, achieving greater specificity in cell identification and isolation than D-DNA-based logic devices. The L-DNA probes realized 98.7% and 70.5% sensitivities in FBS buffer with dual- and triple-aptamer-based logic devices for target cell identification, while D-DNA probes only showed 27.9% and 0.1%. It is believed that the high stability of L-DNA and the high efficiency of the devices for labeling cell subpopulations will have broad applications in the life sciences, biomedical engineering, and personalized medicine.