Table 2.

Materials Considerations in Achieving Compatible Sensor-Biology Interfaces^a

Issues	Importance	Challenges	Solutions and their limitations	Ref
Materials issues				49,50,374,519,520,526,527,535-539
Tissue-like mechanical properties (e.g. Young’s modulus, bending stiffness, stretchability)	Biocompatibility	Intrinsic limitation of electronic materials	Size reduction to the subcellular level: difficult handling and connection, simple functionality	540-543
	Sensor integrity and stability	Microscopic perception by cells	Functional hydrogels: limited performance and functionality, difficult miniaturization	370,372,544-548
	Conformability	Insufficient mechanical match of plastics and elastomers	Soft network materials: complex fabrication, challenging design and fabrication of 3D tissue-like materials	549
	Wearing comfort	Unusual mechanical properties of tissues (e.g., viscoelasticity, J-shape stress-strain curves)	Hierarchical structures: limited fabrication methods and materials	550
			Stiffness-varying polymers: unexplored device integration, unverified biocompatibility	551,552
Tissue adhesion	Conformability	Robustness in dynamic deformation and harsh environmental conditions (e.g., UV light, heat)	Mechanical contact by pressure: discomfort, risk of sensor sliding and friction, associated signal inaccuracy and tissue irritation	553
	Motion artifacts	Robustness on contaminated surfaces (e.g., water, perspiration, skin secretion, cosmetics)	Medical tape: weakened by sweat and water, painful peel-off, no stretchability	554
	Device fixation	On-demand removal without residual or pain	Physical adhesion: only applicable to ultrathin devices	390,555
	Wearing comfort	Biocompatibility	Bioinspired adhesive architectures: complex manufacture, added volume	242,556-558
		Tissue-like mechanical properties	Adhesive hydrogels: large thickness, humidity sensitivity, poor permeability	387-389,546,559-563
			Dry adhesive polymers: limited mechanical compliance, unverified biocompatibility	564-567
			Additional adhesion control layer: one-time use, added volume, weight and complexity	568
Biocompatibility	Health and safety	Intrinsic limitation of electronic materials	Approved materials and biological materials: limited materials choices, limited performance and functionality
	Sensor stability	Lack of knowledge of emerging materials	Surface treatment (nanostructures, hydrogel coatings, etc.): complex fabrication	524,569-571
		Nonhostile immune responses	Biohybrid implants: challenging design and fabrication	528
		Long-term effects	Tissue-like mechanical properties: limitations therein
			Large-scale, systematic tests: lengthy process, application dependence, variance in materials
Biodegradability	Surgical device removal	Whole-device biodegradation	Dissolvable inorganics plus organic substrates: limited choice of materials, risk of high elemental dosage	107,572-574
	Tissue regrowth	Biocompatible degradation products	Functional organics: limited performance and functionality	107,575
	Chronic health risk if not retrieved	Tuneable device lifetime	Components other than sensor outside body: wireless communication limitations, safety risks associated with percutaneous wires	572
			Systemic biocompatibility tests: lengthy process, species dependence
Electrochemical compatibility	Signal-to-noise ratio	Ionic-electronic transduction	Conducting polymers: insufficient conductivity, difficult miniaturization	343,546,547,576,577
	Electrode size (array resolution)	Low frequency signals	Hydrogels and their composites: insufficient conductivity, difficult miniaturization	524,578
	Biocompatibility
Growth adaptability	Conformability	Intrinsic limitation of manmade solid materials	Viscoplastic electronic materials: initial demonstrations only	579
	Biocompatibility	Minimal physical constraint on tissues
	Fast-growing tissues and/or long-term use

^aTheir importance, specific challenges, reported solutions to these challenges, and limitations of the solutions are listed briefly.