Biocompatible and Long-Term Monitoring Strategies of Wearable, Ingestible and Implantable Biosensors: Reform the Next Generation Healthcare
Abstract
:1. Introduction
2. Wearable Biosensors for Healthcare
2.1. Features of Wearable Biosensors and Designing Strategies
2.1.1. Mechanical Biocompatibility
2.1.2. Immune Biocompatibility and Other Desired Features
2.2. Detectable Indicators of Physical Health
2.2.1. Long-Term and Multi-Functional Monitoring of Vital Health Parameters
Detect Target | Material | Structure | Performance | Mechanism | Reference |
---|---|---|---|---|---|
Blood pressure, Heart Rate | Ultrathin gold nanowires, thin polydimethylsiloxane (PDMS) | Sandwich | 13 Pa/17 ms/1.14 kPa−1 | Piezoresistive effect | [54] |
Blood pressure, Heart Rate | Silver-flake, Eco-flex 00-30 silicone rubbers | Triangular-microprism | 63 Pa/0.29 kPa | Triboelectrification effect | [55] |
Blood pressure, Heart Rate | Graphene, PDMS | Hollow | 1.2 ms/15.9 kPa | Piezoresistive effect | [56] |
Blood pressure, Heart Rate | PDMS, Poly(3,4-ethylenedioxythiophene)–poly (styrene sulfonate) (PEDOT:PSS), Aqueous polyurethane dispersion (PUD) | Micro-pyramid array | 23 Pa | Piezoresistive effect | [57] |
Blood pressure, Heart Rate | PDMS, Polyethylene terephthalate (PET) | Micro-pyramid array | 3 Pa/0.55 kPa | Piezo-capacitive effect | [58] |
Blood pressure, Heart Rate | Silicon nanowire (SiNW) | Sandwich | 3 ms/8.2 kPa | Piezo-capacitive effect | [59] |
Respiratory rate, Blood pressure, Heart Rate | Graphene, PDMS | Random distributed spinosum | 25.1 kPa | Piezo-capacitive effect | [60] |
Body temperature | Silk-nanofiber-derived carbon fiber membranes (SilkCFM), PET | Graphitic local structure | 0.81% per centigrade | Thermal resistance effect | [61] |
Bode temperature | Thin and narrow gold | Filamentary serpentine mesh | Millikelvin precision | Thermal resistance effect | [62] |
2.2.2. Physiological Parameters
2.2.3. Non-Invasive Detection of Biochemical Substances
3. Ingestible Biosensors for Healthcare
3.1. Desired Features and Technical Challenges
3.1.1. Locomotion of IBCs
3.1.2. Localization of IBCs
3.1.3. Safety Challenge of IBCs
3.2. Detectable Indicators of Physical Health
3.2.1. Sensing Devices
3.2.2. Operational Devices
4. Implantable Biosensors for Healthcare
4.1. Challenges and Features of Implantable Biosensors
4.1.1. Immune Biocompatibility
4.1.2. Other Desirable Features
4.2. Detectable Indicators of Physical Health
4.2.1. Physiological Signal of Implantable Biosensors
4.2.2. Mechanical Pressure of Implantable Biosensors
4.2.3. Biochemicals of Implantable Biosensors
5. Strategies for Reliable Biosensors
5.1. Strategies to Improve Reliability of Biosensors
5.2. Energy Sources and Power Management of Biosensors
6. Transforming Healthcare Technologies with Biocompatible Biosensors
6.1. A Prototype for the Next Generation Diagnostics
6.2. Integrated Systems for Therapeutic Interventions
6.3. Improvement of Medical Services and Management
7. Concluding Remarks and Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Modalities | Sensing Elements/Sensor Types | Applications # | ||
---|---|---|---|---|
Electrical | Cardiac (ECG) | Heart failure | Advanced skin-attachable electordes | ●[13] |
Muscular (EMG) | Emotional valence | pre-gelled, self-adhesive Ag/AgCl electrodes with inter-electrode spacing [14] | ●[14] | |
Tremor | triaxial accelerometer, triaxial gyroscope, etc. [15] | ●[15] | ||
Posture recognition | a surface EMG acquisition system with EMG acquisition circuit and an MCU with ping-pong buffer designed clock sources | ●[16] | ||
Cerebral (EEG) | Seizure | Subcutaneous devices: 24/7 EEG SubQ™, Minder®, etc. | ●●[17] | |
Surface devices: Behind-the-ear EEG, e-Glasses, Ear-EEG, Sensor dot, etc. | ||||
Physical | Mechanical | Blood pressure/Pulse | Strain sensor or stretch sensor based on piezoelectric effect, piezoresistive effect, triboelectric effect | ●●●[18,19,20,21,22] |
Motion | Strain sensor or stretch sensor based on piezoelectric effect, piezoresistive effect, triboelectric effect, optical fibers, myoelectric sensors | ●●●[23,24,25,26] | ||
Acoustic | Human speech | Strain sensor or stretch sensor based on piezoelectric effect, piezoresistive effect, triboelectric effect; electret condenser microphones; acceleration sensors | ●●[27,28,29] | |
Cardiac/Respiratory sound | Optical sensors (bragg gratting), piezoelectric MEMS acoustic sensor, commercial microphone | ●●[30,31,32,33] | ||
Temperature | Cr/Au metal microwires [34] | ● [34] | ||
Biochemical | In sweat | Glucose | glucose oxidase immobilized within a permeable film of the linear polysaccharide chitosan [34], Pt-decorated graphite or GOx/Pt-graphite [35] | ●●[34,35] |
Lactase | lactate oxidase immobilized within a permeable film of the linear polysaccharide chitosan [34], a reference electrode for the lactate sensor with an internal copolymer of sulphonated polyesther ether sulphone–polyether sulphone (SPEES/PES) membrane as internal layer [36] | ●[34,36] | ||
Na+ | ion-selective electrodes (ISEs) [34,36,37] | ●[34,36]●[37] | ||
Cl− | ion-selective electrodes (ISEs) [34] | ●[34] | ||
K+ | ion-selective electrodes (ISEs) [34] | ●[34] | ||
pH (H+) | H+-selective PANI film that electrochemically deposited onto a Au electrode by cyclic voltammetry [38], Iridium oxide pH electrodes [36] | ●[36]●[38] | ||
Uric acid | CF-reinforced electrode [39] | ●[39] | ||
Cortisol· | MoS2 nanosheets dispersed within the pores of a porous polyamide (PA) membrane [40] | ●●[40] | ||
Alcohol | Electrode casted by mixed droplet of AOx enzyme, BSA stabilizer, and chitosan solution [41] | ●[41] | ||
Ascorbic acid | CF-reinforced electrode [39] | ●[39] | ||
Heavy metal (Hg+, Zn2+, Cd2+, Pb2+, Cu2+) | electrochemical square wave anodic stripping voltammetry (SWASV) on Au and Bi microelectrodes [42] | ●●[42] | ||
Ca2+ | ETH129 as the Ca2+-selective ionophore [38] | ●[38] | ||
NH4+ | ammonium-selective membrane containing nonactin, 2-nitrophenyl octyl ether (o-NPOE) and poly(vinyl chloride) [43] | ●[43] | ||
In interstitial fluid (ISF) | Glucose | a screen-printed layer of Pt/C composite ink [44], Ag/AgCl electrodes [45] | ●[44] | |
Multimodalities | ECG + lactase | ultrasonic transducers (HR and BP), electrochemical sensors (glucose in ISF and lactate, caffeine and alcohol in sweat) [11] | ●[11] | |
ECG + glucose | Self-assembly highly porous PEDOT:PSS hydrogel on paper fiber serving as a low-impedance ECG electrode and a glucose sensor | ●[46] | ||
A hybrid skin patch with MEMS system | ●[47] | |||
Ultrasonic + multiple biomarkers | ultrasonic transducers, electrochemical sensors [48] | ●[48] | ||
sweat metabolites (such as glucose and lactate) + electrolytes (such as Na+ and K+) + skin temperature (to calibrate the response) | ultrasonic transducers, electrochemical sensors, and thermocouple [34] | ●[34] |
Types | Feature | Encapsulation | Life Time | Development Stage | Applications | Year |
---|---|---|---|---|---|---|
(A) IBCs that located in stomach | ||||||
Drug Administration | Less painful, extended/on demand targeted drug release | Stainless steel, PCL [76], Hydrogel [77,108,109], 5-layer BD composite [78] | 3 h [78], 6 h [106], 9 days [76], >1 mth [108] | Proof of concept [77,78], Animal trials [76,108,109] | Targeted on demand drug delivery | 2016, 2018, 2019 |
Biopsy | Magnetic positioning, less invasive & painful procedure | Plastic shell [80], PDMS, SMA Outriggers [79], Aluminum razor [80,81], Polyurethane [110] | indefinite | Proposal [80], Prototype [79], Ex vivo Animal tissue [110] | Biopsy | 2012, 2013, 2014 |
Optical image | BC, minimal electronics, mobile w/magnetic fields | Ice [78], agarose hydrogel [77] | indefinite | Proof of concept [78], Ex vivo [77] | Less invasive surgery | 2016, 2018 |
Ingestion sensor | Skin-worn receiver patch, signficantly reduced size, gastric fluid powered | Edible adhesives [88], Conventional drug tablet powder [74] | 4 min [74] | Commercial product | Medication adherence | 2015, 2020 |
Motility Sensor | Flexiblity & non-battery powered device, dissolvable capsule | Polyamic acid, UV Curable epoxy shell [111], Plastic shell [75] | >10,000 bends [111], 26 h [75] | Proof of concept in vitro & ex vivo [111], in vivo animal trials [75] | Gut motility | 2017, 2019 |
(B) IBCs that located in intestines | ||||||
Drug Administration | Less painful | Stainless steel, PCL | 48 days | Clinical trials [107] | Extended/on extended/on demand targeted drug release | 2019 |
Biopsy | Magnetic position, less invasive & Painful procedure | Plastic shell (Simi et al., 2013), PDMS, SMA outriggers [79], 7075 aluminum razor [80,81], polyurethane [110] | Indefinite | Proposal [80], prototype [79], Ex vivo animal tissue [110] | Biopsy | 2012, 2013, 2014 |
Odometry | Soft & Human compliant, Three-arm design takes stabler & Smoother video | BC rubber wheel & Plastic shell [101] | n/a | Ex vivo [71], Animal testing [101] | Distances between/from landmarks | 2015 |
Spectroscopy (EM Radiation) | Lower manufacturing cost, more accurate & precise results | Non-toxic polycarbonate, shellac coating, BC epoxy | 6 to 9 h | Proof of concept, ex vivo trials [109] | Blood detection | 2016 |
Ultrasound Imaging | Eliminates certain mapping challenges | BC epoxy seal [112], Parylene coating [100] | n/a | Ex vivo | Ultrasound endoscopy/mapping | 2016, 2018 |
Endoscopy | Requires a laxative & fasting for 24 h prior to administration | BC plastics, Teflon coating Shell | 4–12 h | Commercial product [106] | Endoscopy | 2020 |
(C) IBCs that function in whole GI tract | ||||||
Electro-chemical Sensing | Comparable to precision lab equipment | Polyimede flexible substrate, Polyether ether ketone shell | 72 h [93] | Clinical trials | Chemical markers, Disease diagnosis | 2015 |
Temperature | Reliable measurements no matter patient’s activity | BC polycarbonate, Medical-grade plastic | hrs to mths to indefinite [71,113,114] | Commercial product | Core temperature | 2004, 2015, 2020 |
Pressure | Safety, Reliability, Cost, Size | BC polycarbonate, M3 Crystal (resin) | Hrs [100] to mths to indefinite [75] | Commercial product | Pressure, Gut motility | 2018, 2019 |
pH | Miniature & Powerable by many means | BC polycarbonate, Medical-grade plastic | 48 h [114] to 20+ days [71,99] | Commercial product | Gut motility, Stomach acidity, Gastric reflux | 2015, 2017, 2020 |
Gas(CO2, O2, H2) | Linear measurements | BC adhesive, Opaque Polyethelyne Shell | >4 days [68] | Commercial product | Gut disorders (carbohydrate malabsorption, IBS, etc.) | 2017 |
Biomarkers | Modular organic sensor design | Parylene/Epoxy, PDMS Shell | >9 mth [105] | Clinical trials | Bleeding, Infection, Inflammation, etc. | 2018 |
Categories of Biological Information | Detection Target (s) | Application Scenarios | References |
---|---|---|---|
Physiological signals | Electrophysiological signal | Heart failure, Epilepsy, Parkinson’s disease | [125,126] |
Temperature | Thermoregulatory disorder | [90,127] | |
Motion | Parkinson’s disease | [128] | |
Respiratory rate | Asthma | [94,129] | |
Optical signal | Blindness, Cataract | [130] | |
Biochemical signals | DA/AA | Parkinson’s Disease, Schizophrenia, Tics Coprolalia syndrome, Pituitary tumor | [94,131] |
Glucose | Diabetes | [132,133] | |
K+/Na+/Ca2+ | Stroke | [134] | |
pH | Stroke, Traumatic brain injury, Migraine with aura | [64] | |
Mechanical pressure | Intracranial pressure | Intracranial hypertension, Brain tumor, Brain injury | [135] |
Intraocular pressure | Ocular hypertension, Glaucoma. | [136] | |
Pressure in artery | Hypertension | [99,136] | |
Intra-abdominal pressure | Abdominal compartment syndrome | [137] | |
Intra-bladder pressure | Underactive bladder syndrome. | [138] |
Sensors | Types of Power | Detected Signals/Targets | |
---|---|---|---|
Wearable biosensors | Batteries | Glucose [34], Lactate [34,146], pH, Temperature [147], Potassium [146], Li ions [148] | |
PV/Solar cells | Pressure [149], Strain [150] | ||
BFCs | Fructose [151], Glucose [152,153], Exosomes from cell [153], Lactic acid [137,154] | ||
RF harvesters | Location tracking [155] | ||
Energy harvesters | PENGs | Pressure [156], Strain [157], Motion [158], Vibration [159] | |
TENGs | Tactile [160,161], Breathing, pulse [162], Motion [163,164], Strain [165,166] | ||
EMGs | Motion [167] | ||
ESGs | Vibration [168] | ||
TEGs | Temperature [169,170], Pressure [169], Breathing [171], Humidity, Motion [170] | ||
Hybrid energy | TENGs& PENGs | Gait, Sweat [172] | |
TEGs& PENGs | Temperature, Motion, Pulse [173] | ||
TENGs& solar cell | Motion [174] | ||
PV& TEGs | Temperature, Heartbeat, SpO2, Body acceleration [175] | ||
Ingestible biosensors | Batteries | AgO or Li or Li-ion batteries | Temperature [71,109], pH [71,136], Gas [100], Pressure [75,100], Distance [71,101], Motility [71,75,78], Image [71,80,104,109], Biomolecules [105] |
BFCs | Temperature [176], Medication adherence [74] | ||
RF harvesters | Image [177] | ||
Energy harvesters | PENGs | Motility [78] | |
TEGs | Temperature, pH, Iron ions [177] | ||
Implantable biosensors | Batteries | Li batteries | Heart beating [178] |
Li-ion batteries | Neural signals [179] | ||
PV/Solar cells | Optical signal [130] | ||
BFCs | Glucose [142], Disaccharide trehalose [180], Temperature [181], Humidity [127] | ||
Energy harvesters | PENGs | Pressure [182], Vibration [183], Breathing [129], Heart beating [184], Motion [128], Pulse [185], Blood pressure [185] | |
TENGs | Fullness of the bladder [138], Breathing [186], Blood pressure [183,187,188] | ||
EMGs | Heart beating [189,190] |
Modalities | Sensors/Database | Medical Applications | Fusion Technique | Ref. |
---|---|---|---|---|
Images | The JAFFE, the Cohn-Kanade, and the MMI image | Facial expression identification | Gauss–Laguerre wavelet textural feature fusion | [196] |
Electro-Magnetic (EM) tracking and MEMS inertial sensors | A miniature inertial measurement unit and an electromagnetic navigation system | Attitude estimation for laparoscopic surgical tools | An extended Kalman filter | [197] |
Inertia and vision | Inertial and visual motion capture sensors | Knee flexion kinematics for functional rehabilitation movements | An extended Kalman filter | [198] |
Continuous glucose monitoring (CGM) data | CGM sensors | Blood glucose estimation | A K-mean algorithm | [199] |
ECG | MIT-BIH-AR database | Heartbeat classification | A series of one-versus-one SVM binary classifiers | [200] |
Acceleration and ventilation | Hip and wrist accelerometers, Respiratory signals from the AB ventilation sensors | Free-living physical activity assessment | SVM algorithm | [201] |
Acceleration | Wrist accelerometer | Classification of physical activities | Weighted majority vote, Naïve Bayes combination, and Behavior knowledge space combination | [202] |
Daily steps and speed | Wearable or mobile devices | Assessing intensity pattern of lifelogging physical activity | Multiple density map (with Ellipse fitting model to remove irregular uncertainties firstly), Dempster-Shafer theory of evidence (DST) | [203] |
MU-POF | Inertial measurement units (IMUs) intensity-variation based Polymer Optical Fiber (POF) curvature sensor | A knee sleeve for monitoring of physical therapy | Multiparameter fusion (MPF) algorithm | [204] |
Blood flow waveform (BFW) | Wireless cuffless limbs blood sensors | Cardiovascular patients who have high-risk levels of arteriosclerosis | Multiparameter fusion (MPF) algorithm | [205] |
Location | Integration of inertial sensors, Magnetic field and bluetooth low energy (BLE) technologies from the wearable beacon | Identifying low-level micro-activities that can be used to derive complex activities of daily living (ADL) performed by home-care patients | Gathering the location information of the target user by using a wearable beacon embedded with a magnetometer and inertial sensors | [206] |
Gait Speed | Wrist-mounted inertial sensors (wrist-mounted accelerometer and barometer) | Accurate, Long, Real-time, Low-power, and Indoor/Outdoor speed estimation in daily life | A personalized model taking unique gait style of each subject into account | [207] |
Multi-Frequency Electrical Impedance (MFEI) | Electrical impedance measurements | Improve Radiofrequency Ablation Monitoring (RAM) by monitoring of RFA within multiple tissue types | Non-linear machine learning (ML) models | [208] |
IMU | Inertial measurement units (IMUs) securely fixed to body segment | Analyzing hip and knee joint kinematics | Sensor fusion algorithms and a biomechanical model | [209] |
IMU | Wearable IMU (inertial measurement units) sensors | Motor fluctuations in patients with Parkinson’s disease (PD) | Time-frequency (TF) representation and multiway data analysis tools (i.e., tensor decomposition) | [210] |
Respiration, Cardiac Electrical signals, Blood pressures, SpO2 | Sensors of respiration, ECG, Blood pressure, Saturation of oxygen | Remote health care systems | Evidence theory | [211] |
Antenna signals | Antennas, RFID tags | The automatic online recognition of surgical instruments | Layer model with redundant, complementary, Cooperative signal fusion strategies | [212] |
Upper body movements, Force and torque applied to and orientation and position of the surgical instruments | Desktop microphone (audio), Logitech quickcam (bird’s-eye video), Syntek USB Video Capture (surgical field video), ATI mini40 (force and torque), PTI Phoenix VZ3000 (marker locations) | Laparoscopic surgery skill acquisition | The calculation of mechanical energy | [213] |
EEG, Electro-oculogram (EOG), EMG | EEG: low wave energy, sleep spindles, KComplex, delta, theta, stability; EOG: eye movement, correlation, movement activity; EMG: movement activity | Personalized sleep staging system | Evolutionary algorithm and symbolic fusion | [214] |
Joint motion and acceleration | Jaw motion (JM) sensor, Hand gesture (HG) sensor, Accelerometer | Monitoring ingestive behavior | Calculating the product between the JM and HG function, Computing the mean of the acceleration signals | [215] |
Time series, Histopathological images, Knowledge databases, Patient histories | Spanning images, Text, Genomics data | Explainable AI for medical diagnosis and health monitor | Graph neural networks | [216] |
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Lu, T.; Ji, S.; Jin, W.; Yang, Q.; Luo, Q.; Ren, T.-L. Biocompatible and Long-Term Monitoring Strategies of Wearable, Ingestible and Implantable Biosensors: Reform the Next Generation Healthcare. Sensors 2023, 23, 2991. https://doi.org/10.3390/s23062991
Lu T, Ji S, Jin W, Yang Q, Luo Q, Ren T-L. Biocompatible and Long-Term Monitoring Strategies of Wearable, Ingestible and Implantable Biosensors: Reform the Next Generation Healthcare. Sensors. 2023; 23(6):2991. https://doi.org/10.3390/s23062991
Chicago/Turabian StyleLu, Tian, Shourui Ji, Weiqiu Jin, Qisheng Yang, Qingquan Luo, and Tian-Ling Ren. 2023. "Biocompatible and Long-Term Monitoring Strategies of Wearable, Ingestible and Implantable Biosensors: Reform the Next Generation Healthcare" Sensors 23, no. 6: 2991. https://doi.org/10.3390/s23062991
APA StyleLu, T., Ji, S., Jin, W., Yang, Q., Luo, Q., & Ren, T.-L. (2023). Biocompatible and Long-Term Monitoring Strategies of Wearable, Ingestible and Implantable Biosensors: Reform the Next Generation Healthcare. Sensors, 23(6), 2991. https://doi.org/10.3390/s23062991