Wearable Biosensor with Molecularly Imprinted Conductive Polymer Structure to Detect Lentivirus in Aerosol

Abstract

The coronavirus disease (COVID-19) pandemic has increased pressure to develop low-cost, compact, user-friendly, and ubiquitous virus sensors for monitoring infection outbreaks in communities and preventing economic damage resulting from city lockdowns. As proof of concept, we developed a wearable paper-based virus sensor based on a molecular imprinting technique, using a conductive polyaniline (PANI) polymer to detect the lentivirus as a test sample. This sensor detected the lentivirus with a 4181 TU/mL detection limit in liquid and 0.33% to 2.90% detection efficiency in aerosols at distances ranging from 30 cm to 60 cm. For fabrication, a mixture of a PANI monomer solution and virus were polymerized together to form a conductive PANI sensing element on a polyethylene terephthalate (PET) paper substrate. The sensing element exhibited formation of virus recognition sites after the removal of the virus via ultrasound sonication. A dry measurement technique was established that showed aerosol virus detection by the molecularly imprinted sensors within 1.5 h of virus spraying. This was based on the mechanism via which dispensing virus droplets on the PANI sensing element induced hybridization of the virus and molecularly imprinted virus recognition templates in PANI, influencing the conductivity of the PANI film upon drying. Interestingly, the paper-based virus sensor was easily integrated with a wearable face mask for the detection of viruses in aerosols. Since the paper sensor with molecular imprinting of virus recognition sites showed excellent stability in dry conditions for long periods of time, unlike biological reagents, this wearable biosensor will offer an alternative approach to monitoring virus infections in communities.

Keywords: conductive polymer; lentivirus; molecular imprinting; virus sensor; wearable paper sensor.

Figure 1

(a) Photographic image of virus sensor with MIP and NIP electrodes. Scale is 1 cm. (b) Resistivity ratio of the MIP and NIP electrodes as a function of the lentivirus concentration (n = 3, RSD avg. = 3.0%). For calibration, the lentivirus was detected after a 30 min liquid saturation, aspiration, and 30 min natural drying process. (c) Schematic of virus detection mechanism showing polaron hopping and charge transfer in MIP-conductive PANI. The electrical resistance increased from the virus present in the molecularly imprinted cavity. (d) Selectivity test of MIP electrode and comparison to NIP control (represented by dashed line). The resistivity ratios of the lentivirus, retrovirus, latex beads, and human whole blood were calculated from resistance measurements (n ≥ 5, RSD avg. = 13.7%). (e) Diagram of MIP sensing electrode with molecularly imprinted cavities inside the conductive polymer and virus aerosol sprayed onto the sensing element. TU = transducing units; RSD = relative standard deviation.

Figure 2

Resistivity ratio as a function of time and distance (n ≥ 5, RSD avg. = 13.3%). Lentivirus aerosol was sprayed for 10 to 12 s (initial volume of lentivirus solution = 2.65 ± 0.15 mL; approximate virus concentration = 2.2 × 10⁵ TU/mL). (a) Photographic image of the aerosol sprayer and virus detection using sensing electrodes. (b) Resistivity ratios for the MIP and NIP sensing elements as a function of time. (c) Resistivity ratio for the MIP sensing element with and without the virus. DMEM was used as a control without the virus. (d) The resistivity ratio (time = 1.5 h) for the MIP sensing element as a function of sprayer distance. The resistivity ratio for the NIP control was averaged across various distances.

Figure 3

Lentivirus detection using face mask virus sensor. (a) Image of the face mask sensor with NIP and MIP electrodes attached using epoxy. The scale bar is 3 cm. A video is available for download from the Supplemental Materials. (b) The resistivity ratio (time = 1.5 h) of the NIP and MIP electrodes when the face mask was placed 40 cm away from the aerosol sprayer (n = 5, RSD avg. = 0.1%). The inset shows the error bars. (c) Diagnostic test parameters for the virus MIP sensor (n = 20).