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. 2022 Dec 29;13(1):53. doi: 10.3390/bios13010053

Table 2.

Biofunctionalization needs for SiP biosensors. Please note that the performance metrics included in this table are general guidelines and designers should tailor these metrics based on their application. Interdependencies between the different columns of this table should also be considered (e.g., more expensive bioreceptors may still be suitable when combined with patterning techniques that permit very low reagent consumption).

Bioreceptor Immobilization Chemistry Patterning Technique

  • High affinity (KD~nM or lower)

  • Selective (in the ideal case, signal change due to non-specific binding is less than the system limit of detection)

  • Stable (can be stored at ambient conditions with minimal activity loss for times scales on the order of weeks; stable in biological analytes for several hours)

  • Available as validated commercial products

  • Scalable and reproducible production (in the ideal case, variations in target capture due to lot-to-lot variability is less than the system limit of detection)

  • Regenerable or reversible (<5% signal loss between regeneration cycles and >10 consecutive regenerations possible) [82]

  • Small (much smaller than evanescent field decay distance; ~10 nm or less)

  • Low cost (~CAD 1–10/mg)

  • Compatible with Si or Si3N4 surfaces (or native SiO2)

  • Stable (can be stored at ambient conditions for time scales on the order of weeks; stable in biological analytes for several hours)

  • Thin (a few nm or less)

  • Does not introduce a reduction in bioreceptor affinity due to denaturation or random orientation

  • Replicable and uniform (<1 nm intra- and inter-chip variation in immobilization layer thickness)

  • Compatible with system-level sensor integration (e.g., must not damage photonic wire bonds, chip-mounted lasers, or PCB materials)

  • Scalable and simple (does not require highly skilled operators)

  • Mild (no damage to sensor surface or bioreceptors)

  • Resolution ~10 µm or less

  • Multiplexable (multiple reagents can be patterned on different regions of one surface)

  • Uniform spots (<10% spot-to-spot variation; <10% intra-spot variation in bioreceptor loading density) [83]

  • Reproducible (<10% run-to-run variation in spot size, shape, and bioreceptor loading density)

  • High throughput (~10 spots per second or more)

  • Low reagent consumption (minimal reagent waste)

  • Simple (does not require highly skilled operators)

  • Compatible with system-level sensor integration (e.g., must not damage photonic wire bonds, chip-mounted lasers, or PCB materials)

  • No damage to sensor surface or bioreceptors

  • Available as cost-effective commercial products or services

KD: dissociation constant, PCB: printed circuit board.