Table 3.

Biorecognition elements

Biorecognition element	Recognized analytes	Detection mode	Synthesis approach	Inherent amplification	Chemical functionalization	Continuous measurement	Advantages	Disadvantages	Refs.
Enzymes	Metabolites, small molecules	Catalysis	Natural or recombinant production	Yes	Poor	Good	Many enzymes are available for metabolites and substrates; can be extremely sensitive	Stability might be a concern	150,152
Affinity proteins	Metabolites, small molecules, proteins, peptides, nucleic acids, lipids	Direct binding	Natural or recombinant production	No	Poor	Poor	Many affinity proteins are available and well-developed assays for them exist; can be extremely sensitive	Stability might be a concern; considerable effort to create a novel affinity protein	158,264,265
Affinity peptides	Proteins, peptides, nucleic acids, materials	Direct binding	Chemical synthesis	No	Good	Good	Small size; chemical synthesis enables a wide range of functionalizations; very stable	Can exhibit poor sensitivity and specificity	266,267
Aptamers	Metabolites, small molecules, proteins, peptides, nucleic acids, lipids	Direct binding	In vitro synthesis or chemical synthesis	No	Good	Good	Chemical synthesis enables a wide range of functionalizations; some aptamers can be reversibly unfolded	Stability might be a concern owing to nucleases; might require considerable effort to create a novel aptamer	159,268
CRISPR	Nucleic acids	Direct binding or catalysis	Natural or recombinant production	Yes: Cas12, Cas13 and Cas14 only	Poor	Poor	Easy to use; highly programmable for nucleic acid targeting	Probe molecules needed for CRISPR sensing are labile owing to nucleases in sample	28,36,161,163–165,269,270