Skin-Integrated Wearable Systems and Implantable Biosensors: A Comprehensive Review
<p>Biosensor classifications system.</p> "> Figure 2
<p>Skin-integrated biosensor technologies. (<b>a</b>) Carbon nanotube-based pressure sensor for flexible electronics. (i) Photograph of vertically aligned carbon nanotubes (VACNTs) on a Si substrate; (ii) SEM images of VACNTs. The inset shows a high-magnification image highlighting the CNT alignment. (iii) Electrical resistance versus pressure for a VACNT block [<a href="#B37-biosensors-10-00079" class="html-bibr">37</a>]. (<b>b</b>) A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat. (i) Optical image of a fabricated device mounted on the forearm. (ii) FEA results of stress distribution associated with devices on phantom skin (PDMS) and respective optical images under various mechanical distortions: stretching at 30% strain, bending with 5 cm radius, and twisting [<a href="#B40-biosensors-10-00079" class="html-bibr">40</a>]. (<b>c</b>) Electrochemical Tattoo for Real-Time Lactate Monitoring in Human Perspiration: monitoring of sweat lactate during 33 min of cycling exercise while changing the work intensity. (i) Exercise resistance profile on a stationary cycle. Subjects were asked to maintain a constant cycling rate, while the resistance was increased every 3 min for a total evaluation of 30 min. A 3-min cool down period followed the exercise. (ii) An “NE” lactate biosensor applied to a male volunteer’s deltoid; (iii and iv) Response of the LOx- (<b>a</b>) and enzyme-free (<b>b</b>) tattoo biosensors during the exercise regimen (shown in part i) using two representative subjects. Constant potential, +0.05 V (vs. Ag/AgCl); measurement intervals, 1 s [<a href="#B52-biosensors-10-00079" class="html-bibr">52</a>]. (<b>d</b>) Tattoo-based potentiometric ion-selective sensors for epidermal pH monitoring. (<b>e</b>) Influence of repeated mechanical strain (stretching) upon the response of the tattoo ISE: (i) pH-responsive behavior of the ISE tattoo sensor prior to stretching (black) and following the 40th (red) stretch on GORE-TEX; one-unit pH decrement per addition. (ii) Images of the tattoo applied to the forearm at normal, during stretching, and after the 10th stretch [<a href="#B54-biosensors-10-00079" class="html-bibr">54</a>]. (<b>f</b>). Raman spectroscopy system, actual probe setup with a subject, and glucose profile during experiment. (i) Schematic diagram of Raman spectroscopy system for in vivo animal (swine) skin measurement. (ii) Photograph of Raman probe setup. (iii) Glucose profile during the glucose clamping experiment [<a href="#B44-biosensors-10-00079" class="html-bibr">44</a>].</p> "> Figure 3
<p>Strategies for reducing foreign body response (FBR) in implantable biosensors. (<b>a</b>) Dexamethasone-releasing polyurethane coatings for glucose sensors. Micro-CT images of porous coatings created via the salt-leaching/gas-foaming technique with decreasing porogen fraction. The images show coatings of different morphologies created by varying the ammonium bicarbonate porogen concentration. (i) (ii) 90%, (iii) 60% and (iv) 30% [<a href="#B79-biosensors-10-00079" class="html-bibr">79</a>]. (<b>b</b>) In vitro release profiles of poly(lactic-co-glycolic) acid (PLGA) microspheres and PLGA microsphere/PVA hydrogel composite coatings (<span class="html-italic">n</span> = 3 ± SD) at 37 °C, phosphate buffer solution in Polymeric “smart” coating for glucose sensors [<a href="#B82-biosensors-10-00079" class="html-bibr">82</a>].</p> "> Figure 4
<p>In vivo continuous glucose monitoring in mice using the implanted fibers. (<b>a</b>) Schematic illustration of the fluorescent hydrogel fiber designed for long-term in vivo glucose monitoring. (<b>b</b>) The fluorescent polyacrylamide (PAM) hydrogel fibers with and without polyethylene glycol (PEG) were implanted in mouse ears and remained in the mouse ears for one month. The fluorescence intensity of the fiber with PEG was observable through the ear skin for the entire month, whereas the fluorescence intensity of the fiber without PEG was barely detectable after one month. (<b>c</b>) Continuous glucose monitoring using implanted fibers and fluorescence intensity after implantation and after 140 days [<a href="#B86-biosensors-10-00079" class="html-bibr">86</a>].</p> "> Figure 5
<p>In vivo investigation of the developed non-enzymatic continuous glucose monitoring system. (<b>a</b>) Photograph of the developed non-enzymatic continuous glucose monitoring (CGM) and MiniMed CGM as a reference, which were implanted on a rabbit. (<b>b</b>) ISF glucose values measured using the MiniMed CGM (black line with square) and the developed non-enzymatic CGM (red line with circle) in animal experiment [<a href="#B87-biosensors-10-00079" class="html-bibr">87</a>].</p> "> Figure 6
<p>Power supply strategies for implantable biosensors. (<b>a</b>) Sensor implantation: (i) cuff electrodes wrapped around the tibial and peroneal nerves and (ii) implantable device inserted under the back skin of a rabbit [<a href="#B107-biosensors-10-00079" class="html-bibr">107</a>]; (<b>b</b>) Deep brain stimulation (DBS) applications using the flexible indium modified crystalline Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 (PIMNT) energy harvester and characteristics of the flexible PIMNT film (i) a schematic illustration of DBS applications using the flexible PIMNT thin film energy harvester and (ii) a photograph of the final flexible PIMNT harvesting device completely bent by human fingers [<a href="#B109-biosensors-10-00079" class="html-bibr">109</a>].</p> "> Figure 7
<p>Data transmission strategies for implantable biosensors. (<b>a</b>) The implantable sensor small size is achieved by the use of wireless power transfer provided by an external coil and the flexible substrate. The device transmits data via a low energy Bluetooth link to a receiving device; (<b>b</b>) Photos of the implantable neural interface: (i) the neural interface being flexed by a hand, (ii) the top side of the neural interface, (iii) the bottom side of the neural interface [<a href="#B131-biosensors-10-00079" class="html-bibr">131</a>] and (<b>c</b>) illustration of the heart valve monitoring system, which communicates the data by wireless [<a href="#B132-biosensors-10-00079" class="html-bibr">132</a>].</p> "> Figure 8
<p>Fabrication techniques of implantable biosensors. (<b>a</b>) Structure of the polyamide foil with Cu tracks, mounted sensor and encapsulation in Implantable accelerometer system for the determination of blood pressure [<a href="#B135-biosensors-10-00079" class="html-bibr">135</a>]. (<b>b</b>) Schematic illustrations and images of steps for fabricating active, conformal electronics for cardiac electrophysiology. (i) Schematic illustration (left) and optical micrograph (right) of a collection of doped silicon nanomembranes in a unit cell. (ii) Configuration after fabrication of the source, drain, and gate contacts, with suitable interconnects and row electrodes for multiplexed addressing. (iii) Configuration after fabrication of the second metal layer, including the column output electrodes. (iv) Final layout after deposition of encapsulation layers and fabrication of the tissue-contacting electrode [<a href="#B136-biosensors-10-00079" class="html-bibr">136</a>].</p> ">
Abstract
:1. Introduction
2. Biosensors Overview
2.1. Biosensors by Type of Bioreceptor: Catalytic and Affinity Biosensors
2.2. Biosensors by Type of Signal Transduction
3. Biosensors in Medicine
3.1. Skin-Integrated Wearable Biosensors
3.1.1. Sweat Sensors
3.1.2. Bio-Potential Sensors
3.1.3. Tattoo-Like Sensors
3.2. Implantable Biosensors
3.2.1. Glucose Sensors
3.2.2. Bio-Potential Sensors
3.3. Power Supply
3.4. Data Communication
3.5. Fabrication Methods and Current Applications
4. Conclusions and Future Directions
Funding
Conflicts of Interest
References
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Category | Location | Feature/Function | Active Layer | Supporting Layer | Fabrication Method | Reference |
---|---|---|---|---|---|---|
Implantable Biosensors | Heart | Mapping cardiac electrophysiology | Si-based circuits | PI (substrate and dielectric layer) Epoxy (dielectric layer) | Transfer Printing | [136] |
Harvesting mechanical energy from cardiac motions | PZT (capacitor) Au interconnections | PI (substrate) | Litography/Etching/Transfer Printing | [140] | ||
Cardiac electrophysiological mapping | Cr/Au electrodes (rectangular, serpentine shapes) | PDMS | Photolitography/Etching/Transfer Printing | [141] | ||
Electrical cardiac mapping | Cr/Au interconnects (serpentine shape) | Silk (dissolvable substrate) | E-beam evaporation/Photolitography/Etching/Transfer Printing | [65] | ||
Thermal activity | Pt (resistors) Ti/Pt (sensors) Cr/Au interconnects (serpentine shape) | Silk (dissolvable substrate) | E-beam evaporation/Photolitography/Transfer/Printing | [65] | ||
Carotid artery | Monitoring of blood pressure | Cu electrodes | PI substrate | Photolitography | [135] | |
Brain | Mapping brain signals | Au electrode patterns | PI (mesh) Silk (dissolvable substrate) | Photolitography/Ecthing | [139] | |
Mapping neuronal activity | Pt electrodes (contact) Au electrode (base) | PI (substrate) | E-beam Evaporation/ CVD/Transfer Printing | [138] | ||
Neuronal imaging; optogenetic | Graphene Au connection pads | Parylene C | CVD/E-beam evaporation/RIE | [142] | ||
Brain-machine interface; spinal neuromodulation | Au interconnects Pt electrodes | Silicone | Photolitography/Screen-Printing/Thermal evaporation | [143] | ||
Chemical agent delivery; Glutamate sensing | Pt electrodes | PDMS | Photolithography/E-beam evaporation/Etching | [144] | ||
Quantification of pH and O2 | Multi-walled carbon nanotube | Carbon nanotube fibers | CVD | [145] | ||
Monitoring of dopamine | Ethylenedioxythio phene tailored with zwitterionic phosphorylcholine | Carbon fiber | Electropolymerization | [146] | ||
Eye | Retinal stimulation | Boron doped diamond electrodes | PI (substrate) SiO2 (sacrificial layer) | CVD/Etching | [147] | |
Skeletal muscles; skin; heart; brain | Electrical activity measurement | Si and GaAr (serpentine shape) | Modified silicone (substrate) PVA (temporary support) | [25] | ||
Bovine haptoglobin measurement | Gold nanoparticles Multi-walled carbon nanotube | Paper | Printing | [148] | ||
Subdermal dorsal region | Thermal therapy | Mg (conductors) MgO (dielectrics) Si nanomembranes (semiconductors) | Silk (dissolvable substrate) | Transfer Printing/PVD | [58] | |
Peripheral nerve | Glucose sensor for inflammation monitoring | Pt (working electrode) Ag/AgCl (reference electrode) | PI substrate | RIE/Sputtering/Photolitography | [149] |
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Rodrigues, D.; Barbosa, A.I.; Rebelo, R.; Kwon, I.K.; Reis, R.L.; Correlo, V.M. Skin-Integrated Wearable Systems and Implantable Biosensors: A Comprehensive Review. Biosensors 2020, 10, 79. https://doi.org/10.3390/bios10070079
Rodrigues D, Barbosa AI, Rebelo R, Kwon IK, Reis RL, Correlo VM. Skin-Integrated Wearable Systems and Implantable Biosensors: A Comprehensive Review. Biosensors. 2020; 10(7):79. https://doi.org/10.3390/bios10070079
Chicago/Turabian StyleRodrigues, Daniela, Ana I. Barbosa, Rita Rebelo, Il Keun Kwon, Rui L. Reis, and Vitor M. Correlo. 2020. "Skin-Integrated Wearable Systems and Implantable Biosensors: A Comprehensive Review" Biosensors 10, no. 7: 79. https://doi.org/10.3390/bios10070079