Flexible Inkjet-Printed pH Sensors for Application in Organ-on-a-Chip Biomedical Testing

Abstract

Reliable models of the lung environment are important for research on inhalation products, drug delivery, and how aerosols interact with tissue. pH fluctuations frequently accompany real physiological processes in pulmonary environments, so monitoring pH changes in lung-on-a-chip devices is of considerable relevance. Presented here are flexible, miniaturized, inkjet-printed pH sensors that have been developed with the aim of integration into lung-on-a-chip systems. Different types of functional pH-sensitive materials were tested: hydrogen-selective plasticized PVC membranes and polyaniline (both electrodeposited and dropcast). Their deposition and performance were evaluated on different flexible conducting substrates, including screen-printed carbon electrodes (SPE) and inkjet-printed graphene electrodes (IJP-Gr). Finally, a biocompatible dropcast polyaniline-modified IJP was selected and paired with an inkjet-printed Ag/AgCl quasireference electrode. The printed potentiometric device showed Nernstian sensitivity (58.8 mV/pH) with good reproducibility, reversibility, and potential stability. The optimized system was integrated with a developed lung-on-a-chip model with an electrospun polycaprolactone membrane and alginate, simulating the alveolar barrier and the natural mucosal environment, respectively. The permeability of the system was studied by monitoring the pH changes upon the introduction of a 10 wt.% acetic acid aerosol. Overall, the presented approach shows that electrospun-hydrogel materials together with integrated microsensors can help create improved models for studying aerosol transport, diffusion, and chemically changing environments that are relevant for inhalation therapy and respiratory research. These results show that our system can combine mechanical behavior with chemical sensing in one platform, which may be useful for future development of lung-on-a-chip technologies.

Keywords: biomedical testing; electrochemical sensor; flexible sensor; inkjet printing; lung-on-a-chip; pH sensor; polyaniline; potentiometry; printed sensor.

Figure 1

Potential stability testing of chlorinated AgIJPs over 2 h. (A)—AgIJP with electrochemically deposited AgCl (10 s). (B,C)—Chemically deposited AgCl, (C,D)—Electrochemically deposited AgCl. Stability of chlorinated AgIJPs was tested by varying their ionic strength ((B,D)—10⁻¹ M KNO₃, (C,E)—10⁻⁶ M KNO₃) at constant chloride concentration (10⁻¹ M NaCl).

Figure 2

H-ISE prepared on SPEs and IJP-Gr, characterized potentiometrically. (A)—SPEs with ISM dropcast on top of them. (B)—SPEs with spotted ISMs. (C)—IJP-Gr with 4 spots of ISM. All measurements in Figure 2A,B were conducted against an external Ag/AgCl/3M KCl/3M KCl reference electrode. Error bars in (A–C) represent intraelectrode variability (n = 3), while in (C) it represents interelectrode reproducibility (n = 3).

Figure 3

PANI-ED prepared on SPEs (A,B) and IJP-Gr (C,D) electrodes. (A,C)—Cyclic voltammograms showcasing deposition of PANI-ED with each subsequent cycle. (B,D)—Calibration plots for PANI-ED layers deposited in 10 scans (n = 3, intraelectrode reproducibility).

Figure 4

PANI-EB dropcast on SPEs from a THF-EG suspension. (A)—Three consecutive calibration curves on the same electrode. (B,C)—reversibility measured by measuring the pH of standard solutions of decreasing (B) or increasing (C) pH value.

Figure 5

PANI-EB modified IJP-Gr electrodes. (A)—Different amounts of PANI-EB aliquots were tested, with little effect on the sensitivity of the electrodes. (B)—Potential stability of a FIJP system modified with 18 µL of PANI-EB during 6 h immersion in pH 6.4 buffer solution. (C)—Consecutive calibrations on the same FIJP system. (D–F)—Reversibility of the FIJP system.

Figure 6

Lung-on-a-chip measurement. (A)—Photo of a lung-on-a-chip model with the FIJP system, optical micrography of hydrogel (a) and electrospun membrane (b). (B)—pH detection in stationary mode. The inset shows the potential signal while the system is “breathing”. (C)—pH detection in dynamic mode.