Multivalued Logic Assay of the Disease Marker of α-Ketoglutaric Acid by a Luminescent MOF-Based Biosensor.

α-Ketoglutaric acid (α-KA) is an important endogenous metabolite in the Krebs cycle and considered a critical marker for various diseases. Several approaches for identifying α-KA have been reported. However, most of them are limited to single-signal transduction modes in one assay and working in the suspension state, which easily cause quantification errors and lead to false-positive detection results. Herein, a multivalue-responsive and semi-solid EuMOF-gel (EuMOG) logic biosensor is first designed and fabricated, which can realize the specific, rapid, and easy-to-differentiate naked-eye detection of the disease-associated marker of α-KA in serum through implementing one-to-two logic operation with three multicolor gates. The implementation of one-to-two logic operation can be rationally achieved by assembling 2,6-naphthalenedicarboxylic acid as both the energy donor and blue-colored output 1, photoactive Eu3+ ions as the red-emissive output 2, and α-KA stimuli as an input and energy blocker between the dual spectrum-resolved outputs into one unit. With the specific input of α-KA among various analytes, the binary code of the logic decoder switches from (0,1) to (1,0) with an obvious color change from red to cyan. Moreover, by integrating the output chromaticity into the logical operations, the concentration levels of α-KA could be easily evaluated with the intelligent EuMOG detector, which has three multicolor gates in parallel encoding low (0,1), normal (1,1), and danger (1,0) statuses. Such multivalued logic biosensor provides a facile strategy to improve the analysis reliability of disease-associated biomarkers.