A Low-Temperature-Processed, Soft-Fluidic OEGFET Saliva Aptasensor for Cortisol


Label-free, organic field-effect transistor (OFET)-based biosensors have often overlooked a key challenge to commercialization, i.e., process integration. Many promising literature point-of-care (PoC) prototypes are poor integration candidates due to short shelf life, rigid form factor, and reliance on specialized data collection. Our flexible organic electrolyte-gated FET (OEGFET) sensor device architecture is designed to mitigate some of these integration challenges using a novel low temperature, low-cost fabrication process. As a result of the new process, we observed significant improvements in sensor operating parameters over our previous OEGFETs printed using conventional materials, including a 75% reduction in operating voltage (<5 V), 10× superior cortisol detection limit, preserved electrical characteristics (<20% reduction), and laboratory shelf life of over 15 days. We observed excellent repeatability and a predictable distinction between concentration versus output current responses for synthetic samples and complex media, such as spiked saliva supernatant. The device demonstrated a broad detection range of 0.276 pM–27.6 μM for cortisol samples, encompassing the salivary cortisol physiological range. Device specificity to cortisol was observed with progesterone samples, with highly repeatable results and predictable distinctions between binding and nonbinding assays. The fully flexible OEGFET is the first example of an electrolyte-gated OFET biosensor device with integrated soft microfluidic channels, validated using both synthetic and spiked saliva samples.

Date of Publication: January 21, 2022
Electronic ISSN: 2768-167X
Publisher: IEEE
Carleton University, Ottawa, Canada
Carleton University, Ottawa, Canada

1.M. Holzinger, A. Le Goff and S. Cosnier, "Nanomaterials for biosensing applications: A review", Frontiers Chem., vol. 2, pp. 63, Aug. 2014.

2.A. Chen and S. Yang, "Replacing antibodies with aptamers in lateral flow immunoassay", Biosensors Bioelectron., vol. 71, pp. 230-242, Sep. 2015.

3.H. de Puig, I. Bosch, L. Gehrke and K. Hamad-Schifferli, "Challenges of the nano–bio interface in lateral flow and dipstick immunoassays", Trends Biotechnol., vol. 35, no. 12, pp. 1169-1180, Dec. 2017.

4.M. L. Sin, K. E. Mach, P. K. Wong and J. C. Liao, "Advances and challenges in biosensor-based diagnosis of infectious diseases", Expert Rev. Mol. Diagnostics, vol. 14, no. 2, pp. 225-244, Mar. 2014.

5.C. D. Chin, V. Linder and S. K. Sia, "Commercialization of microfluidic point-of-care diagnostic devices", Lab Chip, vol. 12, no. 12, pp. 2118-2134, 2012.

6.M. Gröschl, "Saliva: A reliable sample matrix in bioanalytics", Bioanalysis, vol. 9, no. 8, pp. 655-668, Apr. 2017.

7.D. Narang, M. Kaur, S. Shishodiya and F. Khan, "Saliva as a medium: A new tool in diagnosis", Int. J. Res. Health Allied Sci., vol. 3, no. 4, pp. 56-58, 2018.

8.M. Gröschl, "Current status of salivary hormone analysis", Clin. Chem., vol. 54, no. 11, pp. 1759-1769, Nov. 2008.

9.M. Gröschl, "The physiological role of hormones in saliva", BioEssays, vol. 31, no. 8, pp. 843-852, Aug. 2009.

10.C. Sun, X. Wang, M. Auwalu, S. Cheng and W. Hu, "Organic thin film transistors-based biosensors", EcoMat, vol. 3, no. 2, pp. e12094, 2021.

11.C. Sun et al., "Facile and cost-effective liver cancer diagnosis by water-gated organic field-effect transistors", Biosensors Bioelectron., vol. 164, Sep. 2020.

12.M. J. Iqbal et al., "On the operational shelf life and degradation mechanism in polymer field effect transistors", Superlattices Microstruct., vol. 126, pp. 125-131, Feb. 2019.

13.D. Gupta, N. Jeon and S. Yoo, "Modeling the electrical characteristics of TIPS-pentacene thin-film transistors: Effect of contact barrier field-dependent mobility and traps", Organic Electron., vol. 9, no. 6, pp. 1026-1031, Dec. 2008.

14.H. F. Haneef, A. M. Zeidell and O. D. Jurchescu, "Charge carrier traps in organic semiconductors: A review on the underlying physics and impact on electronic devices", J. Mater. Chem. C, vol. 8, no. 3, pp. 759-787, 2020.

15.C. Feng, O. Marinov, M. J. Deen, P. R. Selvaganapathy and Y. Wu, "Sensitivity of the threshold voltage of organic thin-film transistors to light and water", J. Appl. Phys., vol. 117, no. 18, May 2015.

16.S. Pullano et al., "EGFET-based sensors for bioanalytical applications: A review", Sensors, vol. 18, no. 11, pp. 4042, Nov. 2018.

17.Z. Ni et al., "Quinoline-flanked diketopyrrolopyrrole copolymers breaking through electron mobility over 6 cm² V⁻¹ s⁻¹ in flexible thin film devices", Adv. Mater., vol. 30, no. 10, Mar. 2018.

18.V. Parkula et al., "Harnessing selectivity and sensitivity in electronic biosensing: A novel lab-on-chip multigate organic transistor", Anal. Chem., vol. 92, no. 13, pp. 9330-9337, Jul. 2020.

19.M. Selvaraj et al., "Label free detection of miRNA-21 with electrolyte gated organic field effect transistors (EGOFETs)", Biosensors Bioelectron., vol. 182, Jun. 2021.

20.P. Seshadri et al., "Low-picomolar label-free procalcitonin analytical detection with an electrolyte-gated organic field-effect transistor based electronic immunosensor", Biosensors Bioelectron., vol. 104, pp. 113-119, May 2018.

21.S. K. Sailapu et al., "Standalone operation of an EGOFET for ultra-sensitive detection of HIV", Biosensors Bioelectron., vol. 156, May 2020.

22.S. Sheibani et al., "Extended gate field-effect-transistor for sensing cortisol stress hormone", Commun. Mater., vol. 2, no. 1, pp. 1-10, Dec. 2021.

23.G. M. Ali, "Interdigitated extended gate field effect transistor without reference electrode", J. Electron. Mater., vol. 46, no. 2, pp. 713-717, Feb. 2017.

24.R. S. Massey and R. Prakash, "Flexible organic electrolyte gated FET biosensor with integrated soft fluidics for cortisol monitoring in oral samples", Proc. IEEE Sensors, pp. 1-4, Oct. 2021.

25.R. Massey, E. Morin, M. C. DeRosa and R. Prakash, "Label-free detection of dopamine using aptamer enhanced organic-electrolyte gated FET sensor", Proc. IEEE Int. Conf. Flexible Printable Sensors Syst. (FLEPS), pp. 1-3, Jul. 2019.

26.J. Wasikiewicz et al., "Towards solution processible air stable p-type organic semiconductors: Synthesis and evaluation of mono and di-fluorinated pentacene derivatives", J. Mater. Chem. C, vol. 4, no. 30, pp. 7309-7315, 2016.

27.H. Klauk, "Organic thin-film transistors", Chem. Soc. Rev., vol. 39, no. 7, pp. 2643, Jun. 2010.

28.S. H. Jin, J. S. Yu, C. A. Lee, J. W. Kim, B. Park and J. Lee, "Pentacene OTFTs with PVA gate insulators on a flexible substrate", J.-Korean Phys. Soc., vol. 44, pp. 181-184, Jan. 2004.

29.K. F. Lei, K.-F. Lee and M.-Y. Lee, "Development of a flexible PDMS capacitive pressure sensor for plantar pressure measurement", Microelectron. Eng., vol. 99, pp. 1-5, Nov. 2012.

30.J. A. Martin, J. L. Chávez, Y. Chushak, R. R. Chapleau, J. Hagen and N. Kelley-Loughnane, "Tunable stringency aptamer selection and gold nanoparticle assay for detection of cortisol", Anal. Bioanal. Chem., vol. 406, no. 19, pp. 4637-4647, Jul. 2014.

31.R. Massey and R. Prakash, "Modeling the double layer capacitance effect in electrolyte gated FETs with gel and aqueous electrolytes", Micromachines, vol. 12, no. 12, pp. 1569, Dec. 2021.

32.R. Massey, S. Bebe and R. Prakash, "Aptamer-enhanced organic electrolyte-gated FET biosensor for high-specificity detection of cortisol", IEEE Sensors Lett., vol. 4, no. 7, pp. 1-4, Jun. 2020.

33.M. Debono et al., "Salivary cortisone reflects cortisol exposure under physiological conditions and after hydrocortisone", J. Clin. Endocrinol. Metabolism, vol. 101, no. 4, pp. 1469-1477, Apr. 2016.

34.M. Berto et al., "EGOFET peptide aptasensor for label-free detection of inflammatory cytokines in complex fluids", Adv. Biosyst., vol. 2, no. 2, Feb. 2018.

35.M. Rother et al., "Vertical electrolyte-gated transistors based on printed single-walled carbon nanotubes", ACS Appl. Nano Mater., vol. 1, no. 7, pp. 3616-3624, Jul. 2018.

36.D. Wang, V. Noël and B. Piro, "Electrolytic gated organic field-effect transistors for application in biosensors—A review", Electronics, vol. 5, no. 1, pp. 9, Feb. 2016.

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