Engineering 3D microtip gates of all-polymer organic electrochemical transistors for rapid femtomolar nucleic-acid-based saliva testing.

Point-of-care testing (POCT) of trace amount of biomarkers in biofluids is critical towards health monitoring and early diagnosis. In particular, to facilitate non-invasive saliva testing, the development of low-cost, lightweight and disposable biosensors is in urgent need, while the ultrahigh sensitivity beyond conventional clinical tests remains a great challenge. Herein, we demonstrate a simple and fully printable all-polymer organic electrochemical transistor (OECT) biosensor to detect femtomolar (fM)-level biomolecules in saliva within a few minutes by employing highly conducting lithium bis(trifluoromethanesulfonyl)imide (LiTFSI)-doped poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) serving as both the channel and gate. A 3D microtip-shaped and Au nanoparticle-decorated multiscale gate interface facilitates the sub-fM-level sensing of female hormones (e.g., progesterone) and oligonucleotide cancer biomarkers by aptamers and DNA probes, respectively. Compared to a planar gate, the micro-engineered interface endows the OECT biosensor with significantly lower detection limit by 10-100 times down to <0.1 fM and faster response of <5 min, accomplishing unprecedentedly high sensitivity while maintaining outstanding mechanical flexibility. Consequently, such microtip-gate all-polymer OECT (MAOECT) enables POCT directly in 1000-fold diluted human saliva samples without centrifugation or redox probes, benefiting female fertility monitoring and oral cancer diagnosis as proof-of-concept demonstrations. This straightforward approach presents great potentials in low-cost wearable health management, at-home monitoring and personalized medicine.