Non-invasive Healthcare Analytical Platform Based on Organic Electrochemical Transistors

Abstract

Non-invasive bioelectronics, especially organic electrochemical transistors (OECTs), have drawn extensive attentions of academical and medical communities by virtue of their efficient bio-electronic interfacing, water-involved ionic transport, excellent ionic-electronic coupling, ultralow power consumption, wide detectable range, and outstanding detection sensitivity. Designable structure diversity, low-temperature solution processability, facile bio/chemical functionalization, and excellent biocompatibility of organic mixed ionic-electronic conductors (OMIECs) render OECTs particularly suitable for non-invasive or minimally invasive healthcare analytical platform. Here, we comprehensively review recent advances of the non-invasive analytical healthcare applications based on OECTs, especially on the detection of biomarkers or metabolites in the excretory biofluids, as well as the recording of electrophysiological signals. A brief introduction of OECT and its comparison with other organic thin-film transistors upon device configuration and working mechanism are firstly discussed. State-of-the-art non-invasive OECT-based biosensors are summarized on their detection of ionic and molecular biomarkers, following with circuit design strategies of OECTs for real-time and in-situ electrophysiological recording from skin surface. In conclusion, remaining barriers and future challenges of non-invasive OECT-based bioelectronics towards lower detection limit, more accurate quantitative relationship between analyte concentrations and measured parameters, more intimate device-tissue interface, and long-term operation stability are deeply analyzed with a critical outlook.

References

[[1]] Nawaz A, Liu Q, Leong W L, Fairfull-Smith K E, Sonar P Adv. Mater., 2021, 33: 2101874.

[[2]] Gao W, Emaminejad S, Nyein H Y Y, Challa S, Chen K, Peck A, Fahad H M, Ota H, Shiraki H, Kiriya D, Lien D-H, Brooks G A, Davis R W, Javey A Nature, 2016, 529: 509.

[[3]] Brothers M C, DeBrosse M, Grigsby C C, Naik R R, Hussain S M, Heikenfeld J, Kim S S Acc. Chem. Res., 2019, 52: 297.

[[4]] Moser M, Ponder J F Jr., Wadsworth A, Giovannitti A, McCulloch I Adv. Funct. Mater., 2019, 29: 1807033.

[[5]] Di C, Zhang F, Zhu D Adv. Mater., 2013, 25: 313.

[[6]] Zhao C-X, Liu J-N, Li B-Q, Ren D, Chen X, Yu J, Zhang Q Adv. Funct. Mater., 2020, 30: 2003619.

[[7]] Wang N, Yang A, Fu Y, Li Y, Yan F Acc. Chem. Res., 2019, 52: 277.

[[8]] Song J J, Liu H, Zhao Z Y, Lin P, Yan F Adv. Mater., 2024, 36: 2300034.

[[9]] Rivnay J, Inal S, Salleo A, Owens R M, Berggren M, Malliaras G G Nat. Rev. Mater., 2018, 3: 17086.

[[10]] Jia H, Lei T J. Mater. Chem. C, 2019, 7: 12809.

[[11]] Jia H, Huang Z, Li P, Zhang S, Wang Y, Wang J-Y, Gu X, Lei T J. Mater. Chem. C, 2021, 9: 4927.

[[12]] Hu X, Mao N, Zhao D, Liu X, Sun Q, Yang H, Liu X, Jia H Green Chem. Eng., 2024, 5: 273.

[[13]] Venkatraman V, Friedlein J T, Giovannitti A, Maria I P, McCulloch I, McLeod R R, Rivnay J Adv. Sci., 2018, 5: 1800453.

[[14]] Salim A, Lim S Biosens. Bioelectron., 2019, 141: 111422.

[[15]] Parlak O, Keene S T, Marais A, Curto V F, Salleo A Sci. Adv., 2018, 4: eaar2904.

[[16]] Ohayon D, Nikiforidis G, Savva A, Giugni A, Wustoni S, Palanisamy T, Chen X, Maria I P, Fabrizio E D, Costa P M F J, McCulloch I, Inal S Nat. Mater., 2020, 19: 456.

[[17]] Liang Y, Guo T, Zhou L, Offenhäusser A, Mayer D Materials, 2020, 13: 2577.

[[18]] Braendlein M, Pappa A-M, Ferro M, Lopresti A, Acquaviva C, Mamessier E, Malliaras G G, Owens R M Adv. Mater., 2017, 29: 1605744.

[[19]] Lin P, Yan F, Chan H L W ACS Appl. Mater. Interfaces, 2010, 2: 1637.

[[20]] Go J, Nair P R, Alam M A J. Appl. Phys., 2012, 112: 034516.

[[21]] Dai Y, Dai S, Li N, Li Y, Moser M, Strzalka J, Prominski A, Liu Y, Zhang Q, Li S, Hu H, Liu W, Chatterji S, Cheng P, Tian B, McCulloch I, Xu J, Wang S Adv. Mater., 2022, 34: 2201178.

[[22]] Wu X, Tam T L D, Chen S, Salim T, Zhao X, Zhou Z, Lin M, Xu J, Loo Y-L, Leong W L Adv. Mater., 2022, 34: 2206118.

[[23]] Zhou Z, Wu X, Tam T L D, Tang C G, Chen S, Hou K, Li T, He Q, Sit J-J, Xu J, Leong W L Adv. Funct. Mater., 2024, 34: 2305780.

[[24]] Marks A, Griggs S, Gasparini N, Moser M Adv. Mater. Interfaces, 2022, 9: 2102039.

[[25]] Han S, Yamamoto S, Polyravas A G, Malliaras G G Adv. Mater., 2020, 32: 2004790.

[[26]] Romele P, Gkoupidenis P, Koutsouras D A, Lieberth K, Kovács-Vajna Z M, Blom P W M, Torricelli F Nat. Commun., 2020, 11: 3743.

[[27]] Keene S T, Fogarty D, Cooke R, Casadevall C D, Salleo A, Parlak O Adv. Healthcare Mater., 2019, 8: 1901321.

[[28]] Pappa A M, Ohayon D, Giovannitti A, Maria I P, Savva A, Uguz I, Rivnay J, McCulloch I, Owens R M, Inal S Sci. Adv., 2018, 6: eaat0911.

[[29]] Tang H, Yan F, Lin P, Xu J, Chan H L W Adv. Funct. Mater., 2011, 21: 2264.

[[30]] Burtscher B, Manco Urbina PA, Diacci C, Borghi S, Pinti M, Cossarizza A, Salvarani C, Berggren M, Biscarini F, Simon DT, Bortolotti C A Adv. Healthcare Mater., 2021, 10: 2100955.

[[31]] Liu H, Yang A, Song J, Wang N, Lam P, Li Y, Law H K, Yan F Sci. Adv., 2021, 7: eabg8387.

[[32]] Nyein H Y Y, Gao W, Shahpar Z, Emaminejad S, Challa S, Chen K, Fahad H M, Tai L-C, Ota H, Davis R W, Javey A ACS Nano, 2016, 10: 7216.

[[33]] Lippi G, South A M, Henry B M Ann. Clin. Biochem., 2020, 57: 262.

[[34]] Sessolo M, Rivnay J, Bandiello E, Malliaras G G, Bolink H J Adv. Mater., 2014, 26: 4803.

[[35]] Woeppel A B, Schaefer J, Kim H J, Boudouris B W, Beaudoin SP ACS Appl. Polym. Mater., 2022, 4: 6667.

[[36]] Li T, Cheryl Koh J Y, Moudgil A, Cao H, Wu X, Chen S, Hou K, Surendran A, Stephen M, Tang C, Wang C, Wang Q J, Tay C Y, Leong W L ACS Nano, 2022, 16: 12049.

[[37]] Chen X, Ji J, Peng Y, Gao Z, Zhao M, Tang B, Liu Y J. Mater. Chem. C, 2023, 11: 7722.

[[38]] Wang Y, Wang Y, Zhu R, Tao Y, Chen Y, Liu Q, Liu X, Wang D Mater. Sci. Eng. B, 2022, 278: 115657.

[[39]] Pierre A, Doris S E, Lujan R, Street R A Adv. Mater. Technol., 2019, 4: 1800577.

[[40]] Wustoni S, Combe C, Ohayon D, Akhtar M H, McCulloch I, Inal S Adv. Funct. Mater., 2019, 29: 1904403.

[[41]] Saxena V, Shirodkar V, Prakash R Appl. Biochem. Biotechnol., 2001, 96: 63.

[[42]] Mousavi Z, Ekholm A, Bobacka J, Ivaska A Electroanalysis, 2009, 21: 472.

[[43]] Ghittorelli M, Lingstedt L, Romele P, Crăciun N I, Kovács-Vajna Z M, Blom P W M, Torricelli F Nat. Commun., 2018, 9: 1441.

[[44]] Koutsouras DA, Lieberth K, Torricelli F, Gkoupidenis P, Blom P W M Adv. Mater. Technol., 2021, 6: 2100591.

[[45]] Wu X, Surendran A, Ko J, Filonik O, Herzig EM, Müller-Buschbaum P, Leong W L Adv. Mater., 2019, 31: 1805544.

[[46]] Wang Q, Bai X, Liu F, Li P, Tang Q Microchem. J., 2024, 205: 111260.

[[47]] Chen J, Yang D, Zhu G, Zhang R, Wang B, Chang Z, Dai J, Wu W, Rotenberg M Y, Fang Y Biosens. Bioelectron., 2024, 255: 116229.

[[48]] Jiang X, Shi C, Wang Z, Huang L, Chi L Adv. Mater., 2024, 36: 2308952.

[[49]] Jiang Z, Ye D, Xiang L, He Z, Dai X, Yang J, Xiong Q, Ma Y, Zhi D, Zou Y, Peng Q, Wang S, Li J, Zhang F, Di C Nat. Mater., 2024, 101: 1689

[[50]] Zhang R, Zhao C, Ma W, Yan H ACS Appl. Electron. Mater., 2024, 6: 3431.

[[51]] Liu Z, Song H, Lin G, Zhong W, Zhang Y, Yang A, Liu Y, Duan J, Zhou Y, Jiao K, Ding D, Feng Y, Yue J, Zhao W, Lin X Adv. Sci., 2024, 11: 2400451.

[[52]] Kim Y, Lim T, Kim C-H, Yeo CS, Seo K, Kim S-M, Kim J, Park SY, Ju S, Yoon M-H NPG Asia Mater., 2018, 10: 1086.

[[53]] Wang J, Lee S, Yokota T, Someya T Adv. Funct. Mater., 2022, 32: 2200458.

[[54]] Tarabella G, Villani M, Calestani D, Mosca R, Iannotta S, Zappettini A, Coppedè N J. Mater. Chem., 2012, 22: 23830.

[[55]] Bihar E, Deng Y, Miyake T, Saadaoui M, Malliaras G G, Rolandi M Sci. Rep., 2016, 6: 27582.

[[56]] Ji W, Wu D, Tang W, Xi X, Su Y, Guo X, Liu R Sensor Actuat. B: Chem., 2020, 304: 127414.

[[57]] Lyu X M, Duan Y C, Chen Y L, Cheng S Chem. Res. Chinese Universities, 2023, 39: 877.

[[58]] Fu Y, Wang N, Yang A, Law H K, Li L, Yan F Adv. Mater., 2017, 29: 1703787.

[[59]] Song Y, Zhang H, Mukhopadhyaya T, Hall A S, Katz H E Biosens. Bioelectron., 2022, 216: 114691.

[[60]] Pappa A M, Ohayon D, Giovannitti A, Maria I P, Savva A, Uguz I, Rivnay J, McCulloch I, Owens R M, Inal S Sci. Adv., 2018, 4: eaat0911.

[[61]] Janardhanan J A, Chen L Y, Liu C T, Sheng L H, Tseng H S, Wu P I, She J W, Hsiao S Y, Yu H H Anal. Chem., 2022, 94: 7584.

[[62]] Pappa A M, Curto V F, Braendlein M, Strakosas X, Donahue M J, Fiocchi M, Malliaras G G, Owens R M Adv. Healthcare. Mater., 2016, 5: 2295.

[[63]] Zhang S, Ling H, Chen Y, Cui Q, Ni J, Wang X, Hartel M C, Meng X, Lee K, Lee J, Sun W, Lin H, Emaminejad S, Ahadian S, Ashammakhi N, Dokmeci M R, Khademhosseini A Adv. Funct. Mater., 2020, 30: 1906016.

[[64]] Campana A, Cramer T, Simon DT, Berggren M, Biscarini F Adv. Mater., 2014, 26: 3874.

[[65]] Wu X, Chen S, Moser M, Moudgil A, Griggs S, Marks A, Li T, McCulloch I, Leong W L Adv. Funct. Mater., 2023, 33: 2209354.

[[66]] Park S, Heo S W, Lee W, Inoue D, Jiang Z, Yu K, Jinno H, Hashizume D, Sekino M, Yokota T, Fukuda K, Tajima K, Someya T Nature, 2018, 561: 516.

[[67]] Lee H, Lee S, Lee W, Yokota T, Fukuda K, Someya T Adv. Funct. Mater., 2019, 29: 1906982.

[[68]] Lee W, Kobayashi S, Nagase M, Jimbo Y, Saito I, Inoue Y, Yambe T, Sekino M, Malliaras G G, Yokota T, Tanaka M, Someya T Sci. Adv., 2018, 4: eaau2426.

[[69]] Song J, Liu H, Zhao Z, Guo X, Liu C-K, Griggs S, Marks A, Zhu Y, Law H K-W, McCulloch I, Yan F Sci. Adv., 2023, 9: eadd9627.

[[70]] Chen J, Huang W, Zheng D, Xie Z, Zhuang X, Zhao D, Chen Y, Su N, Chen H, Pankow R M, Gao Z, Yu J, Guo X, Cheng Y, Strzalka J, Yu X, Marks T J, Facchetti A Nat. Mater., 2022, 21: 564.

[[71]] Cea C, Spyropoulos G D, Jastrzebska-Perfect P, Ferrero J J, Gelinas J N, Khodagholy D Nat. Mater., 2020, 19: 679.

[[72]] Yao Y, Huang W, Chen J H, Wang G, Chen H M, Zhuang X M, Ying Y B, Ping J F, Marks T J, Facchetti A Proc. Natl. Acad. Sci. USA, 2021, 118: e2021836118.

[[73]] Spyropoulos G D, Gelinas J N, Khodagholy D Sci. Adv., 2019, 5: eaau7378.

[[74]] Wu M, Yao K, Huang N, Li H, Zhou J, Shi R, Li J, Huang X, Li J, Jia H, Gao Z, Wong T H, Li D, Hou S, Liu Y, Zhang S, Song E, Yu J, Yu X Adv. Sci., 2023, 10: 2300504.

[[75]] Braendlein M, Lonjaret T, Leleux P, Badier J-M, Malliaras G G Adv. Sci., 2017, 4: 1600247.

[[76]] Rivnay J, Leleux P, Sessolo M, Khodagholy D, Hervé T, Fiocchi M, Malliaras GG Adv. Mater., 2013, 25: 7010.

[[77]] Rashid R B, Du W, Griggs S, Maria I P, McCulloch I, Rivnay J Sci. Adv., 2021, 7: eabh1055.

[[78]] Wang J, Lee S, Yokota T, Jimbo Y, Wang Y, Nayeem M O G, Nishinaka M, Someya T ACS Appl. Electron. Mater., 2020, 2: 3601.

[[79]] Zhang R, Zhang J, Tan F, Yang D, Wang B, Dai J, Qi Y, Ran L, He W, Lv Y, Wang F, Fang Y Mater. Today Bio., 2022, 16: 100385.

[[80]] Tang T, Liu Y, Jiang Y Chem. Res. Chinese Universities, 2022, 38: 866.

[[81]] Moudgil A, Hou K, Li T, Leong W L Adv. Mater. Technol., 2023, 8: 2300605.

[[82]] Zhao Z, Tian Z, Yan F Cell Rep. Phys. Sci., 2023, 4: 101673.

[[83]] Moudgil A, Leong W L IEEE Sens. J., 2023, 23: 8028.

[[84]] Li N, Li Y, Cheng Z, Liu Y, Dai Y, Kang S, Li S, Shan N, Wai S, Ziaja A, Wang Y, Strzalka J, Liu W, Zhang C, Gu X, Hubbell J A, Tian B, Wang S Science, 2023, 381: 686.

[[85]] Zhong Y, Saleh A, Inal S Macromol. Biosci., 2021, 21: 2100187.