TABLE 2.

Biological transduction elements at a glance.

Molecular recognition component	Advantages	Disadvantages	Performance		References
			Limit of detection	Sensitivity
Enzymes	- Direct integration of biological recognition facilitates detection via downstream products - Enzyme kinetics may be optimized - Wide variety of chemistries facilitate biosensor integration into optical, electrical, and combinations thereof - Often reversible chemistries	- Structural activity dependence complicates interfacial engineering - Stability and longevity concerns - Kinetically slow enzymes interfere with sensing capacity - Large macromolecular structure limits biotransducer designs	nM–μM May be measured kinetically via U/L (~U/L)	1/μM–1/mM ~1/(U/L)	[151,157,170,174,178]
Aptamers and Peptide Fragments	- Exceptional specificity for target analytes - Genomic DNA is an exceptionally stable biological macromolecule - Precise chemical control - May use DNA and RNA (aptamers) or peptides as needed - Low dimensions facilitate nanomaterial integration - Aptamers facilitate genomic amplification techniques	- Generation of appropriate aptamers is primarily via library trial and error - Affinity based aptameric biosensors may be reversible	fM–nM	1/fM–1/nM In vivo [162]: 1/mM	[178,179,195,196,200,201]
Antibodies	- Excellent specificity - Target recognition of structural motifs facilitates sensing of analyte conformation and modifications - Highest binding affinities of any common biological transducers - Sandwich design immunosensors expand sensing regimes and modalities	- Non-specific binding - Require considerable engineering for appropriate stability - Not conducive to electrical investigation and generally require secondary antibodies, impedance studies, and other supporting chemistries - Low molecular weight analytes cannot be detected	fg/mL–ng/mL	1/(pg/mL)–1/ (μg/mL)	[204,205,208,210,215,216,217,224]
			Most biological analytes (proteins/nucleic acids) detected by antibodies have weights reported in kilodaltons (kDa; equivalent to g/mol). Thus, the molecular weights are in the thousands to hundreds of thousands of g/mol
Supramolecular/Macromolecules	- High stability as organic small molecules - Can participate in sophisticated chemistries with a capacity to retain chemical profile	- Less known - Reconstituting physiological chemistry and performance is non-trivial	Varying Porphyrinic sensors reported down to fM	1/pM–1/μM	[227,229,231,232]