Wearable biosensors for healthcare monitoring

In the paper

“Even so, as described, the sensing device was not integrated with the sweat generation device, but rather coupled to a commercially available Macroduct sweat collector using pilocarpine delivery.”

What the sources say

• Partly supported

  The Results and Discussion and Ex-situ Iontophoresis Sweat Analysis sections describe pilocarpine-induced sweating, followed by collection with a commercial Macroduct collector and separate analysis of the sweat samples. This supports the absence of an integrated sweat-generation device, but the paper does not describe the caffeine sensor as coupled to the Macroduct collector; collection and sensing were sequential steps. (LLM, conf=0.84)

  cites [92] Tai, L. C. et al. Methylxanthine drug monitoring with wearable sweat sensors. Adv. Mater. 30, e1707442 (2018). sourceExperimental — accuracy not yet measured

In the paper

“Although this device is capable of multiplexed sensing, the simultaneous demonstration of two functionalities has not yet been evaluated.”

What the sources say

• Not checked yetcites [117] Kim, J. et al. Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics. Nat. Commun. 8, 14997 (2017). source

In the paper

“This device is capable of detecting salivary lactate electrochemically in connection to selectivity imparted by the lactate oxidase enzyme; protection against biofouling in undiluted human salivary samples was conferred by electro-polymerized ortho-phenylenediamine (OPD) for continuous, non-invasive physiological monitoring of an individual’s fitness state.”

What the sources say

• Not checked yetcites [145] Kim, J. et al. Non-invasive mouthguard biosensor for continuous salivary monitoring of metabolites. Analyst 139, 1632–1636 (2014). source

In the paper

“This platform enables non-invasive monitoring of blood uric acid levels, which is a biomarker for various diseases (e.g., hyperuricemia, gout and renal syndrome), and it displays highly sensitive, selective, stable and rapid response toward obtaining dynamic chemical data on salivary biomarkers in the oral cavity.”

What the sources say

• Not checked yetcites [36] Kim, J. et al. Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics. Biosens. Bioelectron. 74, 1061–1068 (2015). source

In the paper

“However, few studies have focused on developing wearable oral cavity biosensors, likely due to potential biofouling effects caused by the rich salivary protein content and the very low concentration of some target biomarkers.”

In the paper

“However, the toxicity of the device was evaluated without the chemical sensing layer, and hence practical oral-cavity applications would require further critical assessment along with a biocompatible recognition layer.”

What the sources say

• Not checked yetcites [156] Lee, Y. et al. Wireless, intraoral hybrid electronics for real-time quantification of sodium intake toward hypertension management. Proc. Natl Acad. Sci. USA 115, 5377–5382 (2018). source

In the paper

“Compared with other non-invasively sampled biofluids, saliva can be readily sampled without complicated procedures, but is composed of a rich matrix of constituents that can also be easily contaminated by external factors (e.g., food and drink).”

In the paper

“Wearable biosensors face many fundamental challenges and technological gaps related to the scope, validation, stability and accuracy, along with power (Box 1)1,42,157-167, communication (Box 2)1,168 and security/privacy issues (Box 3)1,169-172”

What the sources say

• Not checked yetcites [1] Bandodkar, A. J., Jeerapan, I. & Wang, J. Wearable chemical sensors: present challenges and future prospects. ACS Sens. 1, 464–482 (2016). source
• Not checked yetcites [42] Jeerapan, I., Sempionatto, J. R., Pavinatto, A., You, J. M. & Wang, J. Stretchable biofuel cells as wearable textile-based self-powered sensors. J. Mater. Chem. A Mater. Energy Sustain. 4, 18342–18353 (2016). source
• Not checked yetcites [157] Sarpeshkar, R. Universal principles for ultra low power and energy efficient design. IEEE Trans. Circuits Syst. II 59, 193–198 (2012). source
• Not checked yetcites [158] De Marcellis, A., Depari, A., Ferri, G., Flammini, A. & Sisinni, E. A CMOS integrated low-voltage low-power time-controlled interface for chemical resistive sensors. Sens. Actuators B Chem. 179, 313–318 (2013). source
• Not checked yetcites [159] Zhang, Y. et al. Realizing both high energy and high power densities by twisting three carbon-nanotube-based hybrid fibers. Angew. Chem. Int. Ed. Engl. 54, 11177–11182 (2015). source
• Not checked yetcites [160] Huang, Y. et al. Weavable, conductive yarn-based NiCo//Zn textile battery with high energy density and rate capability. ACS Nano 11, 8953–8961 (2017). source
• Not checked yetcites [161] Mesin, L. A neural algorithm for the non-uniform and adaptive sampling of biomedical data. Comput. Biol. Med. 71, 223–230 (2016). source
• Not checked yetcites [162] Zi, Y. et al. Triboelectric-pyroelectric-piezoelectric hybrid cell for high-efficiency energy-harvesting and self-powered sensing. Adv. Mater. 27, 2340–2347 (2015). source
• Not checked yetcites [163] Zhang, K. & Yang, Y. Thermo-phototronic effect enhanced InP/ZnO nanorod heterojunction solar cells for self-powered wearable electronics. Adv. Funct. Mater. 27, 1703331 (2017). source
• Not checked yetcites [164] Wen, Z. et al. Self-powered textile for wearable electronics by hybridizing fiber-shaped nanogenerators, solar cells, and supercapacitors. Sci. Adv. 2, e1600097 (2016). source

In the paper

“Most current wearable biosensing devices measure a small number of biomarkers.”

In the paper

“Biofouling is driven by the accumulation of proteins, cells or macromolecules on the sensor surface through non-specific binding.”

In the paper

“A plethora of innovative wearable biosensing devices have already been demonstrated in diverse applications, ranging from the detection of metabolites (e.g., lactate or glucose) to the monitoring of electrolytes (e.g., sodium, potassium or calcium) in fluids, such as sweat, ISF, saliva or tears in connection to enzymatic and ion-recognition reactions.”

In the paper

“The concentrations of many important biomarkers in saliva are substantially lower than in blood, requiring highly sensitive sensing systems for accurate monitoring.”

In the paper

“Despite tremendous recent progress in wearable biosensors, the state-of-the-art in this field remains at demonstrating proof-of-concept wearable biosensing platforms for detecting several representative biomarkers, and only small steps can be taken to practical applications in the field.”

In the paper

“Alternatively, wearable batteries have been developed on stretchable and flexible materials for greater wearability, but have not yet demonstrated sufficient energy density for long-term use177-179.”

What the sources say

• Not checked yetcites [177] Xu, S. et al. Stretchable batteries with self-similar serpentine interconnects and integrated wireless recharging systems. Nat. Commun. 4, 1543 (2013). source
• Not checked yetcites [178] Berchmans, S. et al. An epidermal alkaline rechargeable Ag-Zn printable tattoo battery for wearable electronics. J. Mater. Chem. A Mater. 2, 15788–15795 (2014). source
• Not checked yetcites [179] Kumar, R. et al. All-printed, stretchable Zn-Ag2O rechargeable battery via hyperelastic binder for self-powering wearable electronics. Adv. Energy Mater. 7, 1–8 (2017). source

In the paper

“New data mining algorithms are being developed for making sense of the large amount of data and predicting patterns in connection to specific applications.”

In the paper

“The provision of power to wearable biosensing platforms (see Box 1) can be accomplished in several ways, with the most common approach being lithium ion or alkaline batteries.”

In the paper

“These devices exhibit long lifetimes for extended biosensor operation; however, they are relatively bulky and can pose toxicity issues, particularly lithium ion-based systems175,176.”

What the sources say

• Not checked yetcites [175] Hammami, A., Raymond, N. & Armand, M. Lithium-ion batteries: runaway risk of forming toxic compounds. Nature 424, 635–636 (2003). source
• Not checked yetcites [176] Lisbona, D. & Snee, T. A review of hazards associated with primary lithium and lithium-ion batteries. Process Saf. Environ. Prot. 89, 434–442 (2011). source

In the paper

“Unlike traditional (lab-based) biosensors, wearable biosensors can be exposed to harsh and fluctuating conditions (e.g., temperature) during prolonged outdoor activities in uncontrolled environments.”

In the paper

“Wearable biosensors can obviate painful and risky blood sampling procedures and can be readily blended with a wearer’s daily routine.”

In the paper

“Generally, sweat contains metabolites (e.g., lactate, glucose, urea, ethanol or cortisol) along with electrolytes (e.g., sodium, potassium, chloride or ammonium), trace elements (e.g., zinc or copper), and small amounts of large molecules (e.g., proteins, nucleic acids, neuropeptides or cytokines)64.”

What the sources say

• Not checked yetcites [64] Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015). source

In the paper

“Robust, reliable measurement also must overcome such challenges as gradual surface biofouling at the body–sensor interface, inefficient transport of sample over the sensor, limited stability of many bioreceptors, the complexity of multi-step bioaffinity assays and related receptor regeneration, and issues posed by calibration for on-body biosensors.”

In the paper

“Even so, our limited understanding of the correlations between analyte concentrations in the blood and non-invasive biofluids remains a major obstacle.”

In the paper

“Sweat, tears, saliva and ISF have been targeted as they can be sampled in a non-invasive manner, meaning that they can be readily accessed without disrupting the outermost protecting layers of the body’s skin (i.e., stratum corneum) and without contacting blood. As such, non-invasive sensing methods pose minimal risk of harm or infection and are generally more user-friendly.”

In the paper

“Although sweat lactate does not directly reflect the concurrent blood levels, it indicates the level of physical exertion experienced during prolonged exercise and can be used as a marker for athletic efficiency without invasive blood sampling.”

What the sources say

• Not checked yetcites [58] Jia, W. et al. Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration. Anal. Chem. 85, 6553–6560 (2013). source

In the paper

“The reported system proved advantageous for monitoring fitness parameters during exercise, but its utility would be limited in continuous monitoring applications due to its reliance on physical exertion for sweat generation.”

What the sources say

• Not checked yetcites [35] Gao, W. et al. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 529, 509–514 (2016). source

In the paper

“However, the duration of sweat generation was limited to 60 min, with varying rates over that time, which could hinder continuous monitoring applications.”

What the sources say

• Not checked yetcites [41] Emaminejad, S. et al. Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform. Proc. Natl Acad. Sci. USA 114, 4625–4630 (2017). source

In the paper

“However, the efficiency of glucose extraction by RI is difficult to control, which can lead to inconsistent volumes of sampled ISF and thus variations in glucose concentration.”

In the paper

“Although such antibody-based bioassays hold great promise for expanding the scope of epidermal wearable biosensors, which focus primarily on enzymatic metabolite detection, their successful on-body evaluation has yet to be demonstrated.”

In the paper

“Although several studies have indicated that sweat glucose concentrations can correlate with concurrent blood levels, these limitations can significantly impact the accuracy of collected data 64, 76,77.”

What the sources say

• Not checked yetcites [64] Sonner, Z. et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 9, 031301 (2015). source
• Not checked yetcites [76] Moyer, J., Wilson, D., Finkelshtein, I., Wong, B. & Potts, R. Correlation between sweat glucose and blood glucose in subjects with diabetes. Diabetes Technol. Ther. 14, 398–402 (2012). source
• Not checked yetcites [77] Sakaguchi, K. et al. Evaluation of a minimally invasive system for measuring glucose area under the curve during oral glucose tolerance tests: usefulness of sweat monitoring for precise measurement. J. Diabetes Sci. Technol. 7, 678–688 (2013). source

In the paper

“Unlike epidermal enzyme-based biosensors, such immunosensors cannot be readily regenerated toward continuous monitoring applications, and along with other challenges of multi-step affinity bioassays, these devices require further efforts and innovations.”

In the paper

“Yet, these devices require physical exercise for their operation, and are thus not compatible with continuous glucose monitoring in daily-life without exercise.”

In the paper

“Iontophoresis-induced sweat generation obviates the need to exercise for sweat sampling.”

In the paper

“This US Food and Drug Administration (FDA)-approved device is capable of non-invasive glucose monitoring over a 12 hour period with 6 measurements per hour.”

What the sources say

• Not checked yetcites [30] Tierney, M. J., Tamada, J. A., Potts, R. O., Jovanovic, L. & Garg, S. Clinical evaluation of the GlucoWatch biographer: a continual, non-invasive glucose monitor for patients with diabetes. Biosens. Bioelectron. 16, 621–629 (2001). source

In the paper

“Not only do biomarker molecules in tears diffuse directly from the blood and exhibit close tear–blood concentration correlations, but also tear analysis presents opportunities for the diagnosis of ocular disease.”

What the sources say

• Not checked yetcites [94] Farandos, N. M., Yetisen, A. K., Monteiro, M. J., Lowe, C. R. & Yun, S. H. Contact lens sensors in ocular diagnostics. Adv. Healthc. Mater. 4, 792–810 (2015). source
• Not checked yetcites [95] Baca, J. T., Finegold, D. N. & Asher, S. A. Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus. Ocul. Surf. 5, 280–293 (2007). source
• Not checked yetcites [96] Thaysen, J. H. & Thorn, N. A. Excretion of urea, sodium, potassium and chloride in human tears. Am. J. Physiol. 178, 160–164 (1954). source
• Not checked yetcites [97] Mitsubayashi, K. & Arakawa, T. Cavitas sensors: contact lens type sensors & mouthguard sensors. Electroanalysis 28, 1170–1187 (2016). source
• Not checked yetcites [98] Pankratov, D., Gonzalez-Arribas, E., Blum, Z. & Shleev, S. Tear based bioelectronics. Electroanalysis 28, 1250–1266 (2016). source

In the paper

“In particular, tear glucose concentrations have been demonstrated to exhibit good correlation with blood glucose levels, reflecting the diffusion from the lachrymal artery when the tears are sampled without any eye irritation or stimulation, which can compromise the relationship94, 95, 99-101.”

What the sources say

• Not checked yetcites [94] Farandos, N. M., Yetisen, A. K., Monteiro, M. J., Lowe, C. R. & Yun, S. H. Contact lens sensors in ocular diagnostics. Adv. Healthc. Mater. 4, 792–810 (2015). source
• Not checked yetcites [95] Baca, J. T., Finegold, D. N. & Asher, S. A. Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus. Ocul. Surf. 5, 280–293 (2007). source
• Not checked yetcites [99] Sen, D. K. & Sarin, G. S. Tear glucose levels in normal people and in diabetic patients. Br. J. Ophthalmol. 64, 693–695 (1980). source
• Not checked yetcites [100] Chu, M. X. et al. Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment. Talanta 83, 960–965 (2011). source
• Not checked yetcites [101] Chu, M. et al. Biomedical soft contact-lens sensor for in situ ocular biomonitoring of tear contents. Biomed. Microdevices 13, 603–611 (2011). source

In the paper

“Contact lens-based sensors were initially introduced utilizing optical detection of tear glucose levels based on the interaction of glucose with concanavalin A or phenylboronic acid derivatives107,108.”

What the sources say

• Not checked yetcites [107] Alexeev, V. L., Das, S., Finegold, D. N. & Asher, S. A. Photonic crystal glucose-sensing material for noninvasive monitoring of glucose in tear fluid. Clin. Chem. 50, 2353–2360 (2004). source
• Not checked yetcites [108] Ben-Moshe, M., Alexeev, V. L. & Asher, S. A. Fast responsive crystalline colloidal array photonic crystal glucose sensors. Anal. Chem. 78, 5149–5157 (2006). source

In the paper

“Despite the demonstrated correlations, sampling tears for in vitro diagnoses is associated with several errors that are due to the following: first, small sample volumes102; second, ease of evaporation during sample collection; third, variations in tear production among individuals and throughout the day103; and lastly, challenging collection methods that can affect the sampled analyte concentra”

What the sources say

• Not checked yetcites [102] Mishima, S., Gasset, A., Klyce, S. D. Jr. & Baum, J. L. Determination of tear volume and tear flow. Invest. Ophthalmol. 5, 264–276 (1966).
• Not checked yetcites [103] Fullard, R. J. & Carney, L. G. Diurnal variation in human tear enzymes. Exp. Eye Res. 38, 15–26 (1984). source
• Not checked yetcites [104] Yan, Q. et al. Measurement of tear glucose levels with amperometric glucose biosensor/capillary tube configuration. Anal. Chem. 83, 8341–8346 (2011). source
• Not checked yetcites [105] Stuchell, R. N., Feldman, J. J., Farris, R. L. & Mandel, I. D. The effect of collection technique on tear composition. Invest. Ophthalmol. Vis. Sci. 25, 374–377 (1984).

In the paper

“Other contact lens-based optical sensors have involved the use of photonic crystal materials in combination with responsive hydrogels or fluorescent dyes for measuring glucose and other target analytes in tears110-113.”

What the sources say

• Not checked yetcites [110] Khalil, O. S. Noninvasive photonic-crystal material for sensing glucose in tears. Clin. Chem. 50, 2236–2237 (2004). source
• Not checked yetcites [111] Cai, Z., Smith, N. L., Zhang, J. T. & Asher, S. A. Two-dimensional photonic crystal chemical and biomolecular sensors. Anal. Chem. 87, 5013–5025 (2015). source
• Not checked yetcites [112] Elsherif, M., Hassan, M. U., Yetisen, A. K. & Butt, H. Wearable contact lens biosensors for continuous glucose monitoring using smartphones. ACS Nano 12, 5452–5462 (2018). source
• Not checked yetcites [113] Sung, Y., Campa, F. & Shih, W. C. Open-source do-it-yourself multi-color fluorescence smartphone microscopy. Biomed. Opt. Express 8, 5075–5086 (2017). source

In the paper

“Further advances for the field came with the demonstration of electrochemical biosensing by the Parviz team114-116. This group investigated different biosensing strategies to achieve good sensitivity, linearity and accuracy.”

What the sources say

• Not checked yetcites [114] Yao, H., Afanasiev, A., Lahdesmaki, I. & Parviz, B. A. A dual microscale glucose sensor on a contact lens, tested in conditions mimicking the eye. Proc. IEEE Micro. Electro. Mech. Syst. 2011, 25–28 (2011).
• Not checked yetcites [115] Yao, H. et al. A contact lens with integrated telecommunication circuit and sensors for wireless and continuous tear glucose monitoring. J. Micromech. Microeng. 22, 075007 (2012). source
• Not checked yetcites [116] Liao, Y. T., Yao, H. F., Lingley, A., Parviz, B. & Otis, B. P. A. 3-µW CMOS glucose sensor for wireless contact-lens tear glucose monitoring. IEEE J. Solid-State Circuits 47, 335–344 (2012). source

In the paper

“Such sensor placement at the base of the eye (behind the eyelid) provides continuously accessible tear glucose measurements when coupled with wireless data transmission, without causing discomfort.”

What the sources say

• Not checked yetcites [119] Kownacka, A. E. et al. Clinical evidence for use of a noninvasive biosensor for tear glucose as an alternative to painful finger-prick for diabetes management utilizing biopolymer coating. Biomacromolecules 19, 4504–4511 (2018). source

In the paper

“This device offers fast and easy fabrication along with a rapid and sensitive glucose response.”

What the sources say

• Not checked yetcites [112] Elsherif, M., Hassan, M. U., Yetisen, A. K. & Butt, H. Wearable contact lens biosensors for continuous glucose monitoring using smartphones. ACS Nano 12, 5452–5462 (2018). source

In the paper

“Overall, tear-based sensors have been focused primarily on glucose monitoring but show considerable promise for non-invasive sensing of other physiologically important biomarkers.”

In the paper

“Further progress has since been made by embedding a wireless read out chip (2.4 GHz) and by powering with far-field electromagnetic radiation (3μW within 15 cm)116.”

What the sources say

• Not checked yetcites [116] Liao, Y. T., Yao, H. F., Lingley, A., Parviz, B. & Otis, B. P. A. 3-µW CMOS glucose sensor for wireless contact-lens tear glucose monitoring. IEEE J. Solid-State Circuits 47, 335–344 (2012). source

In the paper

“This advanced device focused on ensuring wearer comfort without hindrance to vision through the use of transparent soft materials, while integrating wireless electronics to eliminate the need for an external power source.”

What the sources say

• Not checked yetcites [118] Park, J. et al. Soft, smart contact lenses with integrations of wireless circuits, glucose sensors, and displays. Sci. Adv. 4, eaap9841 (2018). source

In the paper

“As tear fluid contains thousands of proteins—the most abundant of which are lysozyme, lactoferrin and albumin—non-invasive tear monitoring could also be used to detect protein biomarkers correlated with disease121.”

What the sources say

• Not checked yetcites [121] Zhou, L. et al. In-depth analysis of the human tear proteome. J. Proteomics 75, 3877–3885 (2012). source

In the paper

“The high protein content of saliva makes it attractive for detecting disease and stress biomarkers toward biomedical and fitness monitoring.”

In the paper

“Compared with epidermally focused wearable biosensors, tear-based systems benefit from the advantage of continuous access to the target biofluid without the need for induction or extraction.”

In the paper

“However, difficult sampling procedures complicate reliable tear-based sensing platforms while contact lens-type systems suffer from design constraints imposed by the nature of their operating environment.”

In the paper

“Several of these saliva biomarkers (e.g., drug, hormones, metabolites or antibodies) have been used in clinical settings as they offer meaningful diagnostic information140-144.”

What the sources say

• Not checked yetcites [140] Malon, R. S. P., Sadir, S., Balakrishnan, M. & Córcoles, E. P. Saliva-based biosensors: noninvasive monitoring tool for clinical diagnostics. Biomed Res. Int. 2014, 962903 (2014). source
• Not checked yetcites [141] Chicharro, J. L., Lucía, A., Pérez, M., Vaquero, A. F. & Ureña, R. Saliva composition and exercise. Sports Med. 26, 17–27 (1998). source
• Not checked yetcites [142] Singh, M. Non invasive diagnostic tool for pathological conditions salivary biomarkers. Int. J. Pharm. Biol. Arch. 5, 1–12 (2014).
• Not checked yetcites [143] Gatti, R. & De Palo, E. F. An update: salivary hormones and physical exercise. Scand. J. Med. Sci. Sports 21, 157–169 (2011). source
• Not checked yetcites [144] Viswanath, B., Choi, C. S., Lee, K. & Kim, S. Recent trends in the development of diagnostic tools for diabetes mellitus using patient saliva. Trends Analyt. Chem. 89, 60–67 (2017). source

In the paper

“Such a fluidic platform was suggested by the Butt group112 for integration with an optical monitoring system, but has not been demonstrated for biosensing applications.”

What the sources say

• Not checked yetcites [112] Elsherif, M., Hassan, M. U., Yetisen, A. K. & Butt, H. Wearable contact lens biosensors for continuous glucose monitoring using smartphones. ACS Nano 12, 5452–5462 (2018). source

In the paper

“Wearable contact lens tear monitoring platforms are highly advantageous as they do not cause any eye irritation and yield a relatively consistent tear fluid composition.”

In the paper

“Many of the biomarkers in saliva pass directly from the bloodstream via transcellular or paracellular paths, making saliva the “mirror of the human body” that reflects the body’s physiological state to offer a non-invasive alternative to blood analysis.”

In the paper

“Saliva is a complex oral fluid, which is produced mainly by the parotid gland and is composed of numerous constituents, such as metabolites, enzymes, hormones, proteins, microorganisms and ions125,135-140.”

What the sources say

• Not checked yetcites [125] Campuzano, S., Yanez-Sedeno, P. & Pingarron, J. M. Electrochemical bioaffinity sensors for salivary biomarkers detection. Trends Analyt. Chem. 86, 14–24 (2017). source
• Not checked yetcites [135] Aguirre, A. et al. Sialochemistry: a diagnostic tool? Crit. Rev. Oral Biol. Med. 4, 343–350 (1993). source
• Not checked yetcites [136] Kaufman, E. & Lamster, I. B. The diagnostic applications of saliva—a review. Crit. Rev. Oral Biol. Med. 13, 197–212 (2002). source
• Not checked yetcites [137] Chiappin, S., Antonelli, G., Gatti, R. & De Palo, E. F. Saliva specimen: a new laboratory tool for diagnostic and basic investigation. Clin. Chim. Acta 383, 30–40 (2007). source
• Not checked yetcites [138] Streckfus, C. F. & Bigler, L. R. Saliva as a diagnostic fluid. Oral Dis. 8, 69–76 (2002). source
• Not checked yetcites [139] Mandel, I. D. The diagnostic uses of saliva. J. Oral Pathol. Med. 19, 119–125 (1990). source
• Not checked yetcites [140] Malon, R. S. P., Sadir, S., Balakrishnan, M. & Córcoles, E. P. Saliva-based biosensors: noninvasive monitoring tool for clinical diagnostics. Biomed Res. Int. 2014, 962903 (2014). source

In the paper

“However, such in-mouth operation required the replacement of several teeth by the sensors and was subject to risks associated with potential leakage of the internal sensor solution.”

In the paper

“These oral-cavity sensors were integrated with a resonant coil for battery-free operation and were capable of detecting salivary bacteria at the single cell level in vitro using a naturally occurring antimicrobial peptide (AMP) biorecognition element along with label-free impedance transduction.”

What the sources say

• Not checked yetcites [32] Mannoor, M. S. et al. Graphene-based wireless bacteria detection on tooth enamel. Nat. Commun. 3, 763 (2012). source

In the paper

“Despite these challenges, in-mouth biosensing platforms can offer an attractive painless route for obtaining dynamic chemical information from saliva.”

In the paper

“The first example of a wearable oral sensor was demonstrated in the 1960s and was based on a partial denture platform for monitoring mastication monitoring plaque pH and fluoride concentrations.”

In the paper

“In the case of diabetes, changes in hormonal and neural balance may impact the salivary glands, which act as a filter from the blood, and lead to increased secretion of salivary glucose.”

In the paper

“The developed sensors are based on a GOX-modified poly(ethylene terephthalate) glycol (PETG) surface, and the device is seamlessly integrated with a wireless transmitter on a custom-fitted monolithic mouthguard platform.”

What the sources say

• Not checked yetcites [148] Arakawa, T. et al. Mouthguard biosensor with telemetry system for monitoring of saliva glucose: a novel cavitas sensor. Biosens. Bioelectron. 84, 106–111 (2016). source

In the paper

“Soni et al.126 have demonstrated the correlation between blood and saliva glucose concentrations to be R = 0.64 in healthy subjects, whereas diabetic subjects show a much closer relationship with R = 0.95.”

What the sources say

• Not checked yetcites [126] Soni, A. & Jha, S. K. A paper strip based non-invasive glucose biosensor for salivary analysis. Biosens. Bioelectron. 67, 763–768 (2015). source

In the paper

“This configuration enables the telemetric measurement of salivary glucose in artificial saliva over the relevant physiological range (5–1000 μM) and the device has been further characterized through connection to a phantom jaw that mimics the human oral cavity with a saliva flow system.”

What the sources say

• Not checked yetcites [148] Arakawa, T. et al. Mouthguard biosensor with telemetry system for monitoring of saliva glucose: a novel cavitas sensor. Biosens. Bioelectron. 84, 106–111 (2016). source

In the paper

“These advances have greatly enhanced the reliability of wearable biosensor, the analyte monitoring capabilities and wearability.”

In the paper

“Some of these challenges are specific to the individual platforms or target analytes, whereas others are shared by all wearable biosensing systems.”

In the paper

“These demonstrations have shown that wearable biosensors have immense potential for real-world applications.”

In the paper

“Fouling of the surface of wearable biosensors, particularly those operating in sweat or tears over short durations, is expected to be less severe compared with that observed with implantable or minimally-invasive sensors.”

In the paper

“Such dramatic progress has benefited from the refinement of multiplexed-sensing platforms, improved biofluid sampling and advances in flexible materials and wireless electronics.”

In the paper

“A wireless electronic printed circuit board (PCB) containing a fully functional microcontroller is a widely used platform for wireless electronics due to its flexibility and cost-effectiveness.”

In the paper

“Such severe conditions may affect the stability of their fragile bioreceptors.”

In the paper

“These issues can be partially addressed using proper microfluidic sampling systems and optimization of surface coating techniques.”

In the paper

“Multiplexed sensing, including both biosensors and physical sensors, could provide active calibration for variations in temperature, pH and humidity.”

In the paper

“motion with piezoelectric or triboelectric devices185,186”

What the sources say

• Not checked yetcites [185] Yang, J.H. et al. Effect of garment design on piezoelectricity harvesting from joint movement. Smart Mater. Struct. 25, 1–15 (2016). source
• Not checked yetcites [186] Pu, X. et al. Wearable self-charging power textile based on flexible yarn supercapacitors and fabric nanogenerators. Adv. Mater. 28, 98–105 (2016). source

In the paper

“heat with thermoelectric materials187,188”

What the sources say

• Not checked yetcites [187] Oh, J. Y. et al. Chemically exfoliated transition metal dichalcogenide nanosheet-based wearable thermoelectric generators. Energy Environ. Sci. 9, 1696–1705 (2016). source
• Not checked yetcites [188] Lu, Z. S., Zhang, H. H., Mao, C. P. & Li, C. M. Silk fabric-based wearable thermoelectric generator for energy harvesting from the human body. Appl. Energy 164, 57–63 (2016). source

In the paper

“Energy can be harvested from light with wearable solar cells183,184”

What the sources say

• Not checked yetcites [183] O’Connor, T. F. et al. Wearable organic solar cells with high cyclic bending stability: materials selection criteria. Sol. Energy Mater. Sol. Cells 144, 438–444 (2016). source
• Not checked yetcites [184] Kim, B. J. et al. Highly efficient and bending durable perovskite solar cells: toward a wearable power source. Energy Environ. Sci. 8, 916–921 (2015). source

In the paper

“Advances in wearable power sources are a significant need, particularly with increases in energy demands caused by multiplexed sensing platforms.”

In the paper

“The global wearable sensors market was valued at roughly $150 million in 2016 and is projected to reach $2.86 billion by 2025, according to a recent market report (https://www.grandviewresearch.com/industry-analysis/global-wearable-sensor-market).”

What the sources say

• Not checked yetcites https://www.grandviewresearch.com/industry-analysis/global-wearable-sensor-market

In the paper

“The acceptance of these non-invasive biosensors by the medical community will require extensive and successful validation in human testing and improved understanding of the clinical relevancy of sensor information.”

In the paper

“Such future advances, breakthroughs and growth will require close multidisciplinary collaboration among the engineering, scientific and medical communities.”

In the paper

“The sensor preparation thus must ensure high bioreceptor stability for maintaining accuracy and reliability of the response.”

In the paper

“Fully integrated wearable biosensing platforms would require incorporation of wireless electronics (integrated with energy source) to facilitate the data processing and secured signal transmission.”

In the paper

“The regeneration issue of immunosensors is another major challenge to overcome if prolonged use of wearables is to be attained.”

In the paper

“For completely reliable use, wearable devices must overcome stability issues caused by prolonged operation under uncontrolled conditions, biofouling from constituents present in the sampled biofluids, and intrinsic instabilities of the biological recognition components themselves.”

In the paper

“Furthermore, the use of mobile devices and smartphone-based microscopes, including algorithm-based applications, is expected to facilitate the readout of the response in optical wearable biosensors112,113,195.”

What the sources say

• Not checked yetcites [112] Elsherif, M., Hassan, M. U., Yetisen, A. K. & Butt, H. Wearable contact lens biosensors for continuous glucose monitoring using smartphones. ACS Nano 12, 5452–5462 (2018). source
• Not checked yetcites [113] Sung, Y., Campa, F. & Shih, W. C. Open-source do-it-yourself multi-color fluorescence smartphone microscopy. Biomed. Opt. Express 8, 5075–5086 (2017). source
• Not checked yetcites [195] Yetisen, A. K., Martinez-Hurtado, J. L., Garcia-Melendrez, A., Vasconcellos, F. D. & Lowe, C. R. A smartphone algorithm with inter-phone repeatability for the analysis of colorimetric tests. Sens. Actuators B Chem. 196, 156–160 (2014). source

In the paper

“A large portion of this future market share is expected to be made up of wearable biosensors, primarily non-invasive glucose monitoring2.”

What the sources say

• Not checked yetcites [2] Heikenfeld, J. et al. Wearable sensors: modalities, challenges, and prospects. Lab Chip 18, 217–248 (2018). source

In the paper

“Furthermore, the devices must be capable of robust operation without the need for constant (re)calibration (common in laboratory settings).”