REFERENCES
1. Suami, H.; Scaglioni, M. Anatomy of the lymphatic system and the lymphosome concept with reference to lymphedema. Semin. Plast. Surg. 2018, 32, 005-11.
2. Ono, S.; Egawa, G.; Kabashima, K. Regulation of blood vascular permeability in the skin. Inflamm. Regener. 2017, 37, 11.
3. Vermeer, B. J.; Reman, F. C.; Van Gent, C. M. The determination of lipids and proteins in suction blister fluid. J. Investig. Dermatol. 1979, 73, 303-5.
4. Broza, Y. Y.; Zhou, X.; Yuan, M.; et al. Disease detection with molecular biomarkers: from chemistry of body fluids to nature-inspired chemical sensors. Chem. Rev. 2019, 119, 11761-817.
5. Crowley, E.; Di Nicolantonio, F.; Loupakis, F.; Bardelli, A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat. Rev. Clin. Oncol. 2013, 10, 472-84.
6. Alix-panabières, C.; Pantel, K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer. Discovery. 2016, 6, 479-91.
7. Sturgeon, C. M.; Duffy, M. J.; Stenman, U.; et al. National academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin. Chem. 2008, 54, e11-79.
8. Ludwig, J. A.; Weinstein, J. N. Biomarkers in cancer staging, prognosis and treatment selection. Nat. Rev. Cancer. 2005, 5, 845-56.
9. Su, J.; Chen, S.; Dou, Y.; et al. Smartphone-based electrochemical biosensors for directly detecting serum-derived exosomes and monitoring their secretion. Anal. Chem. 2022, 94, 3235-44.
10. Wu, A. H.; Apple, F. S.; Gibler, W. B.; Jesse, R. L.; Warshaw, M. M.; Valdes, R. National academy of clinical biochemistry standards of laboratory practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin. Chem. 1999, 45, 1104-21.
11. Mahato, K.; Wang, J. Electrochemical sensors: from the bench to the skin. Sensor. Actuat. B-Chem. 2021, 344, 130178.
12. Zhou, J. Z.; Kane, S.; Ramsey, C.; et al. Comparison of early- and late-stage breast and colorectal cancer diagnoses during vs before the COVID-19 pandemic. JAMA. Netw. Open. 2022, 5, e2148581.
14. Ward, W. K.; House, J. L.; Birck, J.; Anderson, E. M.; Jansen, L. B. A wire-based dual-analyte sensor for glucose and lactate: in vitro and in vivo evaluation. Diabetes. Technol. The. 2004, 6, 389-401.
15. Chergui, K.; Suaud-Chagny, M.; Gonon, F. Nonlinear relationship between impulse flow, dopamine release and dopamine elimination in the rat brain in vivo. Neuroscience 1994, 62, 641-5.
16. Kraft, J.; Osterhaus, G.; Ortiz, A.; Garris, P.; Johnson, M. In vivo dopamine release and uptake impairments in rats treated with 3-nitropropionic acid. Neuroscience 2009, 161, 940-9.
17. Zhang, J.; Jaquins-Gerstl, A.; Nesbitt, K. M.; Rutan, S. C.; Michael, A. C.; Weber, S. G. In vivo monitoring of serotonin in the striatum of freely moving rats with one minute temporal resolution by online microdialysis-capillary high-performance liquid chromatography at elevated temperature and pressure. Anal. Chem. 2013, 85, 9889-97.
18. Wassum, K. M.; Tolosa, V. M.; Tseng, T. C.; Balleine, B. W.; Monbouquette, H. G.; Maidment, N. T. Transient extracellular glutamate events in the basolateral amygdala track reward-seeking actions. J. Neurosci. 2012, 32, 2734-46.
19. Sarter, M.; Kim, Y. Interpreting chemical neurotransmission in vivo: techniques, time scales, and theories. ACS. Chem. Neurosci. 2014, 6, 8-10.
20. Gaster, R. S.; Hall, D. A.; Nielsen, C. H.; et al. Matrix-insensitive protein assays push the limits of biosensors in medicine. Nat. Med. 2009, 15, 1327-32.
21. Plaxco, K. W.; Soh, H. T. Switch-based biosensors: a new approach towards real-time, in vivo molecular detection. Trends. Biotechnol. 2011, 29, 1-5.
22. Couture, M.; Zhao, S. S.; Masson, J. Modern surface plasmon resonance for bioanalytics and biophysics. Phys. Chem. Chem. Phys. 2013, 15, 11190-216.
23. Marsh, Z. M.; Lantz, K. A.; Stefik, M. QCM detection of molecule-nanoparticle interactions for ligand shells of varying morphology. Nanoscale 2018, 10, 19107-16.
24. Vaisocherová, H.; Brynda, E.; Homola, J. Functionalizable low-fouling coatings for label-free biosensing in complex biological media: advances and applications. Anal. Bioanal. Chem. 2015, 407, 3927-53.
25. Breault-turcot, J.; Masson, J. Microdialysis SPR: diffusion-gated sensing in blood. Chem. Sci. 2015, 6, 4247-54.
26. Arroyo-currás, N.; Somerson, J.; Vieira, P. A.; Ploense, K. L.; Kippin, T. E.; Plaxco, K. W. Real-time measurement of small molecules directly in awake, ambulatory animals. Proc. Natl. Acad. Sci. U.S.A. 2017, 114, 645-50.
27. White, R. J.; Phares, N.; Lubin, A. A.; Xiao, Y.; Plaxco, K. W. Optimization of electrochemical aptamer-based sensors via optimization of probe packing density and surface chemistry. Langmuir 2008, 24, 10513-8.
28. Dauphin-ducharme, P.; Yang, K.; Arroyo-currás, N.; et al. Electrochemical aptamer-based sensors for improved therapeutic drug monitoring and high-precision, feedback-controlled drug delivery. ACS. Sens. 2019, 4, 2832-7.
29. Idili, A.; Arroyo-currás, N.; Ploense, K. L.; et al. Seconds-resolved pharmacokinetic measurements of the chemotherapeutic irinotecan in situ in the living body. Chem. Sci. 2019, 10, 8164-70.
30. Swensen, J. S.; Xiao, Y.; Ferguson, B. S.; et al. Continuous, real-time monitoring of cocaine in undiluted blood serum via a microfluidic, electrochemical aptamer-based sensor. J. Am. Chem. Soc. 2009, 131, 4262-6.
31. Parolo, C.; Idili, A.; Ortega, G.; et al. Real-time monitoring of a protein biomarker. ACS. Sens. 2020, 5, 1877-81.
32. Liu, Y.; Kwa, T.; Revzin, A. Simultaneous detection of cell-secreted TNF-α and IFN-γ using micropatterned aptamer-modified electrodes. Biomaterials 2012, 33, 7347-55.
33. Mayer, M. D.; Lai, R. Y. Effects of redox label location on the performance of an electrochemical aptamer-based tumor necrosis factor-alpha sensor. Talanta 2018, 189, 585-91.
34. Idili, A.; Gerson, J.; Parolo, C.; Kippin, T.; Plaxco, K. W. An electrochemical aptamer-based sensor for the rapid and convenient measurement of l-tryptophan. Anal. Bioanal. Chem. 2019, 411, 4629-35.
35. Idili, A.; Parolo, C.; Ortega, G.; Plaxco, K. W. Calibration-free measurement of phenylalanine levels in the blood using an electrochemical aptamer-based sensor suitable for point-of-care applications. ACS. Sens. 2019, 4, 3227-33.
36. Arroyo-Currás, N.; Dauphin-Ducharme, P.; Ortega, G.; Ploense, K. L.; Kippin, T. E.; Plaxco, K. W. Subsecond-resolved molecular measurements in the living body using chronoamperometrically interrogated aptamer-based sensors. ACS. Sens. 2017, 3, 360-6.
37. Arroyo-currás, N.; Ortega, G.; Copp, D. A.; et al. High-precision control of plasma drug levels using feedback-controlled dosing. ACS. Pharmacol. Transl. Sci. 2018, 1, 110-8.
38. Anitha, K.; Posinasetty, B.; Naveen Kumari, K.; et al. Liquid biopsy for precision diagnostics and therapeutics. Clin. Chim. Acta. 2024, 554, 117746.
39. Zhou, Y.; Tao, L.; Qiu, J.; et al. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Sig. Transduct. Target. Ther. 2024, 9, 132.
40. Yu, M.; Tyson, C.; Limburg, P. J.; Beer, T. M. A flexible quantitative framework to assess the potential contribution of early cancer detection to improved cancer survival. J. Clin. Oncol. 2023, 41, e22508.
41. Childs, A.; Mayol, B.; Lasalde-Ramírez, J. A.; Song, Y.; Sempionatto, J. R.; Gao, W. Diving into sweat: advances, challenges, and future directions in wearable sweat sensing. ACS. Nano. 2024, 18, 24605-16.
42. Davis, N.; Heikenfeld, J.; Milla, C.; Javey, A. The challenges and promise of sweat sensing. Nat. Biotechnol. 2024, 42, 860-71.
43. Heikenfeld, J.; Jajack, A.; Feldman, B.; et al. Accessing analytes in biofluids for peripheral biochemical monitoring. Nat. Biotechnol. 2019, 37, 407-19.
44. Tran, B. Q.; Miller, P. R.; Taylor, R. M.; et al. Proteomic characterization of dermal interstitial fluid extracted using a novel microneedle-assisted technique. J. Proteome. Res. 2017, 17, 479-85.
45. Taylor, R. M.; Miller, P. R.; Ebrahimi, P.; Polsky, R.; Baca, J. T. Minimally-invasive, microneedle-array extraction of interstitial fluid for comprehensive biomedical applications: transcriptomics, proteomics, metabolomics, exosome research, and biomarker identification. Lab. Anim. 2018, 52, 526-30.
46. Miller, P. R.; Taylor, R. M.; Tran, B. Q.; et al. Extraction and biomolecular analysis of dermal interstitial fluid collected with hollow microneedles. Commun. Biol. 2018, 1, 173.
47. Davis, M. J.; Rahbar, E.; Gashev, A. A.; Zawieja, D. C.; Moore, J. E. Determinants of valve gating in collecting lymphatic vessels from rat mesentery. Am. J. Physiol.-Heart. C. 2011, 301, H48-60.
48. Mendoza, E.; Schmid-Scho¨nbein, G. W. A model for mechanics of primary lymphatic valves. J. Biomech. Eng. 2003, 125, 407-14.
49. Bendayan, M. Morphological and cytochemical aspects of capillary permeability. Microsc. Res. Tech. 2002, 57, 327-49.
50. Vink, H.; Duling, B. R. Capillary endothelial surface layer selectively reduces plasma solute distribution volume. Am. J. Physiol.-Heart. C. 2000, 278, H285-9.
52. Tuma, P. L.; Hubbard, A. L. Transcytosis: crossing cellular barriers. Physiol. Rev. 2003, 83, 871-932.
53. Geyer, P. E.; Holdt, L. M.; Teupser, D.; Mann, M. Revisiting biomarker discovery by plasma proteomics. Mol. Syst. Biol. 2017, 13, MSB156297.
55. Zhang, Z.; Zhang, M.; Chen, S.; Horbett, T. A.; Ratner, B. D.; Jiang, S. Blood compatibility of surfaces with superlow protein adsorption. Biomaterials 2008, 29, 4285-91.
56. Anderson, N. L.; Anderson, N. G. The human plasma proteome. Mol. Cell. Proteomics. 2002, 1, 845-67.
58. Hower, J. C.; Bernards, M. T.; Chen, S.; Tsao, H.; Sheng, Y.; Jiang, S. Hydration of “nonfouling” functional groups. J. Phys. Chem. B. 2008, 113, 197-201.
59. Lavery, K. S.; Rhodes, C.; Mcgraw, A.; Eppihimer, M. J. Anti-thrombotic technologies for medical devices. Adv. Drug. Delivery. Rev. 2017, 112, 2-11.
60. Jaffer, I. H.; Weitz, J. I. The blood compatibility challenge. Part 1: blood-contacting medical devices: the scope of the problem. Acta. Biomater. 2019, 94, 2-10.
61. Wallace, A.; Albadawi, H.; Patel, N.; et al. Anti-fouling strategies for central venous catheters. Cardiovasc. Diagn. Ther. 2017, 7. Suppl, S246-57.
62. Wilson, C. J.; Clegg, R. E.; Leavesley, D. I.; Pearcy, M. J. Mediation of biomaterial-cell interactions by adsorbed proteins: a review. Tissue. Eng. 2005, 11, 1-18.
63. Singha, P.; Locklin, J.; Handa, H. A review of the recent advances in antimicrobial coatings for urinary catheters. Acta. Biomater. 2017, 50, 20-40.
64. Gupta, P.; Sarkar, S.; Das, B.; Bhattacharjee, S.; Tribedi, P. Biofilm, pathogenesis and prevention - a journey to break the wall: a review. Arch. Microbiol. 2015, 198, 1-15.
65. Plachouras, D.; Lepape, A.; Suetens, C. ECDC definitions and methods for the surveillance of healthcare-associated infections in intensive care units. Intensive. Care. Med. 2018, 44, 2216-8.
66. Kostakioti, M.; Hadjifrangiskou, M.; Hultgren, S. J. Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. CSH. Perspect. Med. 2013, 3, a010306.
67. Kolluru, C.; Williams, M.; Chae, J.; Prausnitz, M. R. Recruitment and collection of dermal interstitial fluid using a microneedle patch. Adv. Healthc. Mater. 2019, 8, 1801262.
68. Laszlo, E.; De Crescenzo, G.; Nieto-argüello, A.; Banquy, X.; Brambilla, D. Superswelling microneedle arrays for dermal interstitial fluid (prote)omics. Adv. Funct. Mater. 2021, 31, 2106061.
69. Himawan, A.; Vora, L. K.; Permana, A. D.; et al. Where microneedle meets biomarkers: futuristic application for diagnosing and monitoring localized external organ diseases. Adv. Healthc. Mater. 2022, 12, 2202066.
70. Xu, D.; Guo, D.; Zhang, J.; et al. Innovative tumor interstitial fluid-triggered carbon dot-docetaxel nanoassemblies for targeted drug delivery and imaging of HER2-positive breast cancer. Int. J. Pharm. 2024, 657, 124145.
71. Jasuja, H.; Jaswandkar, S. V.; Katti, D. R.; Katti, K. S. Interstitial fluid flow contributes to prostate cancer invasion and migration to bone; study conducted using a novel horizontal flow bioreactor. Biofabrication 2023, 15, 025017.
72. Acs, M.; Acs, R.; Briandi, C.; Eubanks, E.; Rehman, O.; Zhuang, H. Exploration of the relevance of microRNA signatures for cancer detection and multiclass cancer classification. IEEE. Access. 2023, 11, 57268-84.
73. Yan, S.; Zheng, H.; Zhao, J.; Gao, M.; Zhang, X. Quantification of GPC1(+) exosomes based on MALDI-TOF MS in situ signal amplification for pancreatic cancer discrimination and evaluation. Anal. Chem. 2023, 95, 10196-203.
74. Chen, Y.; Gao, D.; Zhu, Q.; et al. Rapid exosome isolation and in situ multiplexed detection of exosomal surface proteins and microRNAs on microfluidic platform. Analyst 2023, 148, 2387-94.
75. Fogh-Andersen, N.; Altura, B. M.; Altura, B. T.; Siggaard-Andersen, O. Composition of interstitial fluid. Clin. Chem. 1995, 41, 1522-5.
76. Al Sulaiman, D.; Chang, J. Y. H.; Bennett, N. R.; et al. Hydrogel-coated microneedle arrays for minimally invasive sampling and sensing of specific circulating nucleic acids from skin interstitial fluid. ACS. Nano. 2019, 13, 9620-8.
77. Li, Y.; Wang, Y.; Mei, R.; et al. Hydrogel-coated SERS microneedles for drug monitoring in dermal interstitial fluid. ACS. Sens. 2024, 9, 2567-74.
78. Watkins, Z.; Karajic, A.; Young, T.; White, R.; Heikenfeld, J. Week-long operation of electrochemical aptamer sensors: new insights into self-assembled monolayer degradation mechanisms and solutions for stability in serum at body temperature. ACS. Sens. 2023, 8, 1119-31.
79. Harder, J.; Schröder, J. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J. Biol. Chem. 2002, 277, 46779-84.
80. Shukla, S.; Machekposhti, S. A.; Joshi, N.; Joshi, P.; Narayan, R. J. Microneedle-integrated device for transdermal sampling and analyses of targeted biomarkers. Small. Sci. 2023, 3, 2200087.
81. Facchinetti, A.; Sparacino, G.; Cobelli, C. Reconstruction of glucose in plasma from interstitial fluid continuous glucose monitoring data: role of sensor calibration. J. Diabetes. Sci. Technol. 2007, 1, 617-23.
82. Shao, J.; Li, X.; Li, Y.; Lin, J.; Huang, P. Self-heating multistage microneedle patch for topical therapy of skin cancer. Adv. Mater. 2024, 36, 2308217.
83. Sonner, Z.; Wilder, E.; Heikenfeld, J.; et al. The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. Biomicrofluidics 2015, 9, 031301.
84. Luchini, A.; Fredolini, C.; Espina, B.; et al. Nanoparticle technology: addressing the fundamental roadblocks to protein biomarker discovery. Curr. Mol. Med. 2010, 10, 133-41.
85. Boysen, T. C.; Yanagawa, S.; Sato, F.; Sato, K. A modified anaerobic method of sweat collection. J. Appl. Physiol. 1984, 56, 1302-7.
86. Jajack, A.; Brothers, M.; Kasting, G.; Heikenfeld, J. Enhancing glucose flux into sweat by increasing paracellular permeability of the sweat gland. PLoS. ONE. 2018, 13, e0200009.
87. Crandall, C. G. Mechanisms and controllers of eccrine sweating in humans. Front. Biosci. 2010, S2, 685-96.
88. Hianik, T.; Ostatná, V.; Sonlajtnerova, M.; Grman, I. Influence of ionic strength, pH and aptamer configuration for binding affinity to thrombin. Bioelectrochemistry 2007, 70, 127-33.
89. Csősz, É.; Emri, G.; Kalló, G.; Tsaprailis, G.; Tőzsér, J. Highly abundant defense proteins in human sweat as revealed by targeted proteomics and label-free quantification mass spectrometry. J. Eur. Acad. Dermatol. Venereol. 2015, 29, 2024-31.
90. Gao, W.; Emaminejad, S.; Nyein, H. Y. Y.; et al. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 2016, 529, 509-14.
91. Jia, M.; Chew, W. M.; Feinstein, Y.; Skeath, P.; Sternberg, E. M. Quantification of cortisol in human eccrine sweat by liquid chromatography - tandem mass spectrometry. Analyst 2016, 141, 2053-60.
92. Heikenfeld, J. Non-invasive analyte access and sensing through eccrine sweat: challenges and outlook circa 2016. Electroanalysis 2016, 28, 1242-9.
93. Leung, K. K.; Gerson, J.; Emmons, N.; Heemstra, J. M.; Kippin, T. E.; Plaxco, K. W. The use of xenonucleic acids significantly reduces the in vivo drift of electrochemical aptamer-based sensors. Angew. Chem. Int. Ed. 2024, 63, e202316678.
94. Vallée-bélisle, A.; Ricci, F.; Plaxco, K. W. Thermodynamic basis for the optimization of binding-induced biomolecular switches and structure-switching biosensors. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 13802-7.
95. Lin, S.; Cheng, X.; Zhu, J.; et al. Wearable microneedle-based electrochemical aptamer biosensing for precision dosing of drugs with narrow therapeutic windows. Sci. Adv. 2022, 8, eabq4539.
96. Bakhshandeh, F.; Zheng, H.; Barra, N. G.; et al. Wearable aptalyzer integrates microneedle and electrochemical sensing for in vivo monitoring of glucose and lactate in live animals. Adv. Mater. 2024, 36, 2313743.
97. Ye, C.; Wang, M.; Min, J.; et al. A wearable aptamer nanobiosensor for non-invasive female hormone monitoring. Nat. Nanotechnol. 2023, 19, 330-7.
98. He, R.; Liu, H.; Niu, Y.; Zhang, H.; Genin, G. M.; Xu, F. Flexible miniaturized sensor technologies for long-term physiological monitoring. npj. Flex. Electron. 2022, 6, 20.
99. Han, S.; Yamamoto, S.; Jung, C.; Jin, D. Y.; Lee, T.; Kim, J. Wearable sensors for monitoring chronic kidney disease. Commun. Mater. 2024, 5, 153.
100. Timpel, J.; Klinghammer, S.; Riemenschneider, L.; et al. Sensors for in situ monitoring of oral and dental health parameters in saliva. Clin. Oral. Investig. 2023, 27, 5719-36.
101. Pandit, P.; Crewther, B.; Cook, C.; Punyadeera, C.; Pandey, A. K. Sensing methods for stress biomarker detection in human saliva: a new frontier for wearable electronics and biosensing. Mater. Adv. 2024, 5, 5339-50.
102. Li, X.; Liu, S.; Huang, X.; et al. Aptamers-based wearable electrochemical sensors for continuous monitoring of biomarkers in vivo. Microsyst. Nanoeng. 2025, 11, 241.
103. Holmlin, R. E.; Chen, X.; Chapman, R. G.; Takayama, S.; Whitesides, G. M. Zwitterionic SAMs that resist nonspecific adsorption of protein from aqueous buffer. Langmuir 2001, 17, 2841-50.
104. Ferguson, B. S.; Hoggarth, D. A.; Maliniak, D.; et al. Real-time, aptamer-based tracking of circulating therapeutic agents in living animals. Sci. Transl. Med. 2013, 5.
105. Seo, J.; Fu, K.; Correa, S.; Eisenstein, M.; Appel, E. A.; Soh, H. T. Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals. Sci. Adv. 2022, 8, eabk2901.
106. Fu, K.; Seo, J. W.; Kesler, V.; et al. Accelerated electron transfer in nanostructured electrodes improves the sensitivity of electrochemical biosensors. Adv. Sci. 2021, 8, 2102495.
107. Downs, A. M.; Gerson, J.; Hossain, M. N.; et al. Nanoporous gold for the miniaturization of in vivo electrochemical aptamer-based sensors. ACS. Sens. 2021, 6, 2299-306.
108. Daggumati, P.; Matharu, Z.; Seker, E. Effect of nanoporous gold thin film morphology on electrochemical DNA sensing. Anal. Chem. 2015, 87, 8149-56.
109. Yang, W.; Gerasimov, J. Y.; Lai, R. Y. Folding-based electrochemical DNA sensor fabricated on a gold-plated screen-printed carbon electrode. Chem. Commun. 2009, 2902.
110. Matharu, Z.; Daggumati, P.; Wang, L.; Dorofeeva, T. S.; Li, Z.; Seker, E. Nanoporous-gold-based electrode morphology libraries for investigating structure-property relationships in nucleic acid based electrochemical biosensors. ACS. Appl. Mater. Interfaces. 2017, 9, 12959-66.
111. Arroyo-currás, N.; Scida, K.; Ploense, K. L.; Kippin, T. E.; Plaxco, K. W. High surface area electrodes generated via electrochemical roughening improve the signaling of electrochemical aptamer-based biosensors. Anal. Chem. 2017, 89, 12185-91.
112. Welsh, J. B.; Psavko, S.; Zhang, X.; Gao, P.; Balo, A. K. Comparisons of fifth-, sixth-, and seventh-generation continuous glucose monitoring systems. J. Diabetes. Sci. Technol. 2022, 18, 143-7.
113. Battelino, T.; Alexander, C. M.; Amiel, S. A.; et al. Continuous glucose monitoring and metrics for clinical trials: an international consensus statement. Lancet. Diabetes. Endo. 2023, 11, 42-57.
114. Chmayssem, A.; Nadolska, M.; Tubbs, E.; et al. Insight into continuous glucose monitoring: from medical basics to commercialized devices. Microchim. Acta. 2023, 190, 177.
115. Downs, A. M.; Bolotsky, A.; Weaver, B. M.; et al. Microneedle electrochemical aptamer-based sensing: real-time small molecule measurements using sensor-embedded, commercially-available stainless steel microneedles. Biosens. Bioelectron. 2023, 236, 115408.
116. Reynoso, M.; Chang, A.; Wu, Y.; et al. 3D-printed, aptamer-based microneedle sensor arrays using magnetic placement on live rats for pharmacokinetic measurements in interstitial fluid. Biosens. Bioelectron. 2024, 244, 115802.
117. Wu, Y.; Tehrani, F.; Teymourian, H.; et al. Microneedle aptamer-based sensors for continuous, real-time therapeutic drug monitoring. Anal. Chem. 2022, 94, 8335-45.
118. Keyvani, F.; Ghavaminejad, P.; Saleh, M. A.; et al. Integrated electrochemical aptamer biosensing and colorimetric pH monitoring via hydrogel microneedle assays for assessing antibiotic treatment. Adv. Sci. 2024, 11, 2309027.
119. Chiang, P.; Lin, X.; Shin, S.; et al. Real-time and continuous L-tryptophan monitoring by electrochemical aptamer-enabled microneedle sensor array. Sensor. Actuat. B-Chem. 2026, 449, 139056.
120. Yue Jing, L.; Fan, Y.; Zhi Chen, B.; et al. An aptamer-integrated conductive microneedle biosensor for real-time transdermal cortisol monitoring. Chem. Eng. J. 2024, 502, 157488.
121. Keyvani, F.; Zheng, H.; Kaysir, M. R.; et al. A hydrogel microneedle assay combined with nucleic acid probes for on-site detection of small molecules and proteins. Angew. Chem. Int. Ed. 2023, 62, e202301624.
122. Yuan, R.; Cai, J.; Li, J.; et al. Integrated microneedle aptasensing platform toward point-of-care monitoring of bacterial infections and treatment. ACS. Sens. 2025, 10, 5684-93.
123. Fakeih, E.; Shetty, S. S.; Hanif, W.; Mutabagani, K.; Salama, K. N.; Alsulaiman, D. A Microneedle-based Ige aptasensor for transdermal detection of food allergy sensitization. ACS. Materials. Lett. 2025, 7, 3595-603.
124. Friedel, M.; Werbovetz, B.; Drexelius, A.; et al. Continuous molecular monitoring of human dermal interstitial fluid with microneedle-enabled electrochemical aptamer sensors. Lab. Chip. 2023, 23, 3289-99.
125. Chen, S.; Li, L.; Zhao, C.; Zheng, J. Surface hydration: Principles and applications toward low-fouling/nonfouling biomaterials. Polymer 2010, 51, 5283-93.
126. Kesler, V.; Fu, K.; Chen, Y.; et al. Tailoring electrode surface charge to achieve discrimination and quantification of chemically similar small molecules with electrochemical aptamers. Adv. Funct. Mater. 2022, 33, 2208534.
127. Mcgowan, M. P.; Trowbridge, A. J.; Reitemeier, J.; Jordan, K. M.; Fu, K. X. Surface charge effects of monovalent and zwitterionic monolayers to differentiate structurally similar aminoglycosides with electrochemical aptamer biosensors. Biosens. Bioelectron. 2025, 276, 117229.
128. Li, S.; Wang, Y.; Zhang, Z.; Wang, Y.; Li, H.; Xia, F. Exploring end-group effect of alkanethiol self-assembled monolayers on electrochemical aptamer-based sensors in biological fluids. Anal. Chem. 2021, 93, 5849-55.
129. Li, H.; Dauphin-Ducharme, P.; Arroyo-Currás, N.; et al. A biomimetic phosphatidylcholine-terminated monolayer greatly improves the in vivo performance of electrochemical aptamer-based sensors. Angew. Chem. Int. Ed. 2017, 56, 7492-5.
130. Duan, H.; Peng, S.; He, S.; et al. Antifouling zwitterionic coating enhances electrochemical aptamer-based sensors for therapeutic drug monitoring. Nano. Today. 2026, 66, 102892.
131. Kim, S.; Gim, T.; Jeong, Y.; Ryu, J. H.; Kang, S. M. Facile construction of robust multilayered PEG films on polydopamine-coated solid substrates for marine antifouling applications. ACS. Appl. Mater. Interfaces. 2017, 10, 7626-31.
132. Chen, Y.; Fu, K. X.; Cotton, R.; et al. A biochemical sensor with continuous extended stability in vivo. Nat. Biomed. Eng. 2025, 9, 1517-30.
133. Li, S.; Dai, J.; Zhu, M.; et al. Implantable hydrogel-protective DNA aptamer-based sensor supports accurate, continuous electrochemical analysis of drugs at multiple sites in living rats. ACS. Nano. 2023, 17, 18525-38.
134. Huldin, G. F.; Huang, J.; Reitemeier, J.; Fu, K. X. Nafion coated nanopore electrode for improving electrochemical aptamer-based biosensing. Faraday. Discuss. 2025, 257, 316-32.
135. Wang, C.; Fan, K.; Shirzaei Sani, E.; et al. A microfluidic wearable device for wound exudate management and analysis in human chronic wounds. Sci. Transl. Med. 2025, 17, eadt0882.
136. Wang, M.; Ye, C.; Yang, Y.; et al. Printable molecule-selective core-shell nanoparticles for wearable and implantable sensing. Nat. Mater. 2025, 24, 589-98.
137. Xu, C.; Song, Y.; Sempionatto, J. R.; et al. A physicochemical-sensing electronic skin for stress response monitoring. Nat. Electron. 2024, 7, 168-79.
138. Song, Y.; Tay, R. Y.; Li, J.; et al. 3D-printed epifluidic electronic skin for machine learning–powered multimodal health surveillance. Sci. Adv. 2023, 9, eadi6492.
139. Min, J.; Demchyshyn, S.; Sempionatto, J. R.; et al. An autonomous wearable biosensor powered by a perovskite solar cell. Nat. Electron. 2023, 6, 630-41.
140. Tu, J.; Min, J.; Song, Y.; et al. A wireless patch for the monitoring of C-reactive protein in sweat. Nat. Biomed. Eng. 2023, 7, 1293-306.
141. Wang, B.; Zhao, C.; Wang, Z.; et al. Wearable aptamer-field-effect transistor sensing system for noninvasive cortisol monitoring. Sci. Adv. 2022, 8, eabk0967.
142. Zhang, X.; Tang, Y.; Wu, H.; Wang, Y.; Niu, L.; Li, F. Integrated aptasensor array for sweat drug analysis. Anal. Chem. 2022, 94, 7936-43.
143. Zhang, X.; Zhang, J.; Cai, Y.; et al. Integrated electrochemical aptasensor array toward monitoring anticancer drugs in sweat. Anal. Chem. 2024, 96, 4997-5005.
144. Fu, J.; Wang, Y.; Ding, Y.; et al. Wearable ring sensor for monitoring biomarkers of atherosclerosis in sweat. Talanta 2025, 287, 127608.
145. Huang, C.; Li, D.; Liu, J.; et al. A flexible aptameric graphene field-effect nanosensor capable of automatic liquid collection/filtering for cytokine storm biomarker monitoring in undiluted sweat. Adv. Funct. Mater. 2023, 34, 2309447.
146. Gao, Y.; Nguyen, D. T.; Yeo, T.; et al. A flexible multiplexed immunosensor for point-of-care in situ wound monitoring. Sci. Adv. 2021, 7, eabg9614.
147. Huang, C.; Yang, W.; Wang, H.; et al. Flexible/regenerative nanosensor with automatic sweat collection for cytokine storm biomarker detection. ACS. Nano. 2024, 18, 21198-210.
148. Gao, W.; Ota, H.; Kiriya, D.; Takei, K.; Javey, A. Flexible electronics toward wearable sensing. Acc. Chem. Res. 2019, 52, 523-33.
149. Chen, S.; Qiao, Z.; Niu, Y.; et al. Wearable flexible microfluidic sensing technologies. Nat. Rev. Bioeng. 2023, 1, 950-71.
150. Xu, Y.; Ye, Z.; Zhao, G.; et al. Phase-separated porous nanocomposite with ultralow percolation threshold for wireless bioelectronics. Nat. Nanotechnol. 2024, 19, 1158-67.
151. Eiler, J.; Hansen, D.; Bingöl, B.; Hansen, K.; Heikenfeld, J.; Thormann, E. In vitro evaluation of skin adhesives during perspiration. Int. J. Adhes. Adhes. 2020, 99, 102574.
152. Si, Y.; Li, C.; Hu, J.; Zhang, C.; Dong, Z. Bioinspired superwetting open microfluidics: from concepts, phenomena to applications. Adv. Funct. Mater. 2023, 33, 2301017.
153. Sun, Y.; Wang, J.; Lu, Q.; et al. Stretchable and smart wettable sensing patch with guided liquid flow for multiplexed in situ perspiration analysis. ACS. Nano. 2024, 18, 2335-45.
154. He, X.; Xu, T.; Gu, Z.; et al. Flexible and superwettable bands as a platform toward sweat sampling and sensing. Anal. Chem. 2019, 91, 4296-300.
155. Yang, H.; Ji, S.; Chaturvedi, I.; et al. Adhesive biocomposite electrodes on sweaty skin for long-term continuous electrophysiological monitoring. ACS. Mater. Lett. 2020, 2, 478-84.
156. Yuan, Q.; Fang, H.; Wu, X.; et al. Self-adhesive, biocompatible, wearable microfluidics with erasable liquid metal plasmonic hotspots for glucose detection in sweat. ACS. Appl. Mater. Interfaces. 2023, 16, 66810-8.
157. Choi, Y.; Jin, P.; Lee, S.; et al. All-printed chip-less wearable neuromorphic system for multimodal physicochemical health monitoring. Nat. Commun. 2025, 16, 5689.
158. Lu, Y.; Yang, G.; Wang, S.; et al. Stretchable graphene-hydrogel interfaces for wearable and implantable bioelectronics. Nat. Electron. 2023, 7, 51-65.
159. Sonner, Z.; Wilder, E.; Gaillard, T.; Kasting, G.; Heikenfeld, J. Integrated sudomotor axon reflex sweat stimulation for continuous sweat analyte analysis with individuals at rest. Lab. Chip. 2017, 17, 2550-60.
160. Li, S.; Li, C.; Wang, Y.; Li, H.; Xia, F. Re-engineering electrochemical aptamer-based biosensors to tune their useful dynamic range via distal-site mutation and allosteric inhibition. Anal. Chem. 2020, 92, 13427-33.
161. Singh, N. K.; Chung, S.; Chang, A.; Wang, J.; Hall, D. A. A non-invasive wearable stress patch for real-time cortisol monitoring using a pseudoknot-assisted aptamer. Biosens. Bioelectron. 2023, 227, 115097.
162. Downs, A. M.; Plaxco, K. W. Real-time, in vivo molecular monitoring using electrochemical aptamer based sensors: opportunities and challenges. ACS. Sens. 2022, 7, 2823-32.
163. Ogden, N. E.; Kurnik, M.; Parolo, C.; Plaxco, K. W. An electrochemical scaffold sensor for rapid syphilis diagnosis. Analyst 2019, 144, 5277-83.
164. Kang, D.; Parolo, C.; Sun, S.; Ogden, N. E.; Dahlquist, F. W.; Plaxco, K. W. Expanding the scope of protein-detecting electrochemical DNA “scaffold” sensors. ACS. Sens. 2018, 3, 1271-5.
165. Ma, J.; Zhu, J.; Li, J.; Yang, Y. Design of a cost-effective inverted tetrahedral DNA nanostructure - based interfacial probe for electrochemical biosensing with enhanced performance. Microchem. J. 2021, 168, 106455.
166. Lin, M.; Wan, H.; Zhang, J.; Wang, Q.; Hu, X.; Xia, F. Electrochemical DNA sensors based on MoS2-AuNPs for polynucleotide kinase activity and inhibition assay. ACS. Appl. Mater. Interfaces. 2020, 12, 45814-21.
167. Lai, R. Y. Folding- and dynamics-based electrochemical DNA sensors. In Enzymes as Sensors; Methods in Enzymology, Vol. 589; Elsevier, 2017; pp 221-52.
168. Shen, Q.; Fan, M.; Yang, Y.; Zhang, H. Electrochemical DNA sensor-based strategy for sensitive detection of DNA demethylation and DNA demethylase activity. Anal. Chim. Acta. 2016, 934, 66-71.
169. Idili, A.; Amodio, A.; Vidonis, M.; Feinberg-somerson, J.; Castronovo, M.; Ricci, F. Folding-upon-binding and signal-on electrochemical DNA sensor with high affinity and specificity. Anal. Chem. 2014, 86, 9013-9.
170. Luo, X.; Du, F.; Wu, Y.; Gao, L.; Li, X. Electrochemical DNA sensor for determination of p53 tumor suppressor gene incorporating gold nanoparticles modification. Chin. J. Anal. Chem. 2013, 41, 1664-8.
171. Li, H.; Li, S.; Dai, J.; et al. High frequency, calibration-free molecular measurements in situ in the living body. Chem. Sci. 2019, 10, 10843-8.
172. Li, H.; Dauphin-ducharme, P.; Ortega, G.; Plaxco, K. W. Calibration-free electrochemical biosensors supporting accurate molecular measurements directly in undiluted whole blood. J. Am. Chem. Soc. 2017, 139, 11207-13.
173. Lee, T.; Chen, L.; Wang, E.; Wang, C.; Lin, Y.; Chen, W. Development of an electrochemical immunosensor for detection of cardiac troponin I at the point-of-care. Biosensors 2021, 11, 210.
174. Feng, X.; Gan, N.; Lin, S.; et al. Ratiometric electrochemiluminescent aptasensor array for antibiotic based on internal standard method and spatial-resolved technique. Sensor. Actuat. B-Chem. 2016, 226, 305-11.
175. Chen, Z.; Wang, Y.; Du, X.; Sun, J.; Yang, S. Temperature-alternated electrochemical aptamer-based biosensor for calibration-free and sensitive molecular measurements in an unprocessed actual sample. Anal. Chem. 2021, 93, 7843-50.
176. Du, Y.; Lim, B. J.; Li, B.; Jiang, Y. S.; Sessler, J. L.; Ellington, A. D. Reagentless, ratiometric electrochemical DNA sensors with improved robustness and reproducibility. Anal. Chem. 2014, 86, 8010-6.
177. Leung, K. K.; Downs, A. M.; Ortega, G.; Kurnik, M.; Plaxco, K. W. Elucidating the mechanisms underlying the signal drift of electrochemical aptamer-based sensors in whole blood. ACS. Sens. 2021, 6, 3340-7.
178. Verrinder, E.; Gerson, J.; Leung, K.; Kippin, T. E.; Plaxco, K. W. Dual-frequency, ratiometric approaches to EAB sensor interrogation support the calibration-free measurement of specific molecules in vivo. ACS. Sens. 2024, 9, 3205-11.
179. Downs, A. M.; Gerson, J.; Leung, K. K.; Honeywell, K. M.; Kippin, T.; Plaxco, K. W. Improved calibration of electrochemical aptamer-based sensors. Sci. Rep. 2022, 12, 5535.
180. Zupančič, U.; Jolly, P.; Estrela, P.; Moschou, D.; Ingber, D. E. Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood. Adv. Funct. Mater. 2021, 31, 2010638.
181. Torrente-rodríguez, R. M.; Lukas, H.; Tu, J.; et al. SARS-CoV-2 RapidPlex: a graphene-based multiplexed telemedicine platform for rapid and low-cost COVID-19 diagnosis and monitoring. Matter 2020, 3, 1981-98.
182. Cui, F.; Yue, Y.; Zhang, Y.; Zhang, Z.; Zhou, H. S. Advancing biosensors with machine learning. ACS. Sens. 2020, 5, 3346-64.
183. Xue, Y.; Ji, W.; Jiang, Y.; Yu, P.; Mao, L. Deep learning for voltammetric sensing in a living animal brain. Angew. Chem. Int. Ed. 2021, 60, 23777-83.
184. Ali, M.; Naeem, F.; Tariq, M.; Kaddoum, G. Federated learning for privacy preservation in smart healthcare systems: a comprehensive survey. IEEE. J. Biomed. Health. Inform. 2023, 27, 778-89.
185. Jiang, C.; Wang, G.; Hein, R.; Liu, N.; Luo, X.; Davis, J. J. Antifouling strategies for selective in vitro and in vivo sensing. Chem. Rev. 2020, 120, 3852-89.
186. Sabaté Del Río, J.; Henry, O. Y. F.; Jolly, P.; Ingber, D. E. An antifouling coating that enables affinity-based electrochemical biosensing in complex biological fluids. Nat. Nanotechnol. 2019, 14, 1143-9.
187. Jaffer, I.; Fredenburgh, J.; Hirsh, J.; Weitz, J. Medical device-induced thrombosis: what causes it and how can we prevent it? J. Thromb. Haemost. 2015, 13, S72-81.
188. Weber, M.; Steinle, H.; Golombek, S.; et al. Blood-contacting biomaterials: in vitro evaluation of the hemocompatibility. Front. Bioeng. Biotechnol. 2018, 6, 99.
189. Khatoon, Z.; Mctiernan, C. D.; Suuronen, E. J.; Mah, T.; Alarcon, E. I. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon 2018, 4, e01067.
190. Caldara, M.; Belgiovine, C.; Secchi, E.; Rusconi, R. Environmental, microbiological, and immunological features of bacterial biofilms associated with implanted medical devices. Clin. Microbiol. Rev. 2022, 35, e00221-20.
191. Samant, P. P.; Prausnitz, M. R. Mechanisms of sampling interstitial fluid from skin using a microneedle patch. Proc. Natl. Acad. Sci. U.S.A. 2018, 115, 4583-8.
192. Kolluru, C.; Williams, M.; Yeh, J. S.; Noel, R. K.; Knaack, J.; Prausnitz, M. R. Monitoring drug pharmacokinetics and immunologic biomarkers in dermal interstitial fluid using a microneedle patch. Biomed. Microdevices. 2019, 21, 14.
193. Gromov, P.; Gromova, I.; Olsen, C. J.; et al. Tumor interstitial fluid - a treasure trove of cancer biomarkers. BBA-Proteins. Proteom. 2013, 1834, 2259-70.
194. Wiig, H.; Swartz, M. A. Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer. Physiol. Rev. 2012, 92, 1005-60.
195. Min, J.; Tu, J.; Xu, C.; et al. Skin-interfaced wearable sweat sensors for precision medicine. Chem. Rev. 2023, 123, 5049-138.
196. Yang, D. S.; Ghaffari, R.; Rogers, J. A. Sweat as a diagnostic biofluid. Science 2023, 379, 760-1.
197. Sempionatto, J. R.; Lasalde-Ramírez, J. A.; Mahato, K.; Wang, J.; Gao, W. Wearable chemical sensors for biomarker discovery in the omics era. Nat. Rev. Chem. 2022, 6, 899-915.
198. Yang, Y.; Gao, W. Wearable and flexible electronics for continuous molecular monitoring. Chem. Soc. Rev. 2019, 48, 1465-91.
199. Malon, R. S. P.; Sadir, S.; Balakrishnan, M.; Córcoles, E. P. Saliva-based biosensors: noninvasive monitoring tool for clinical diagnostics. Biomed. Res. Int. 2014, 2014, 1-20.
200. Sterzenbach, T.; Helbig, R.; Hannig, C.; Hannig, M. Bioadhesion in the oral cavity and approaches for biofilm management by surface modifications. Clin. Oral. Investig. 2020, 24, 4237-60.
201. Qin, S.; Jie, Z.; Chen, L.; et al. Real-time monitoring of daunorubicin pharmacokinetics with nanoporous electrochemical aptamer-based sensors in vivo. Sensor. Actuat. B-Chem. 2024, 411, 135710.
202. Booth, M. A.; Erdal, M. K.; Larson, M.; et al. Pilot phase clinical trial of a wearable, electrochemical aptamer-based patch for continuous drug concentration measurement. Nat. Biotechnol. 2026, 3010.
