Modulation of chemical functional groups on conducting polymers (CPs) provides an effective way to tailor the physicochemical properties and electrochemical performance of CPs, as well as serves as a functional interface for stable integration of CPs with biomolecules for organic bioelectronics (OBEs). Herein, we introduced a facile approach to modulate the carboxylate functional groups on the PEDOT interface through a systematic evaluation on the effect of a series of carboxylate-containing molecules as counterion dopant integrated into the PEDOT backbone, including acetate as monocarboxylate (mono-COO-), malate as dicarboxylate (di-COO-), citrate as tricarboxylate (tri-COO-), and poly(acrylamide-co-acrylate) as polycarboxylate (poly-COO-) bearing different amounts of molecular carboxylate moieties to create tunable PEDOT:COO- interfaces with improved polymerization efficiency. We demonstrated the modulation of PEDOT:COO- interfaces with various granulated morphologies from 0.33 to 0.11 mu m, tunable surface carboxylate densities from 0.56 to 3.6 mu M cm(-2), and with improved electrochemical kinetics and cycling stability. We further demonstrated the effective and stable coupling of an enzyme model lactate dehydrogenase (LDH) with the optimized PEDOT:poly-COO- interface via simple covalent chemistry to develop biofunctionalized PEDOT (Bio-PEDOT) as a lactate biosensor. The biosensing mechanism is driven by a sequential bioelectrochemical signal transduction between the bio-organic LDH and organic PEDOT toward the concept of all-polymer-based OBEs with a high sensitivity of 8.38 mu A mM(-1) cm(-2) and good reproducibility. Moreover, we utilized the LDH-PEDOT biosensor for the detection of lactate in spiked serum samples with a high recovery value of 91-96% and relatively small RSD in the range of 2.1-3.1%. Our findings provide a new insight into the design and optimization of functional CPs, leading to the development of new OBEs for sensing, biosensing, bioengineering, and biofuel cell applications.
