Biosensor development using organic electrochemical transistors (OECTs) fabricated via printing techniques
Creators: Fan, Jiaxin
Publisher: name: University of Alberta Library
Year: 2022

<p>Continuous health monitoring and integrated diagnostic devices are revolutionizing the modern healthcare system. Biosensors serve as an essential tool in detecting and monitoring a wide range of medical conditions from diabetes to cancer for precision healthcare. The global biosensor market value was 22.4 billion USD in 2020 and is expected to reach 41.8 billion USD by 2028. In 2020, the medical segment accounted for 66.6% of the biosensor market revenue. The invention of conducting polymer, which has excellent properties, paved the path for creating inexpensive organic electronics for biosensing. Organic electrochemical transistors (OECTs) have emerged as a versatile biosensing platform due to their low operation voltages, compatibility with aqueous environments, and intrinsic signal amplification. Owing to the simple device structure, OECTs are compatible with 3D printing technology that enables rapid customization of biosensing platforms to meet specific requirements. </p>

<p>In this work, OECTs are fabricated and optimized using two different 3D printing systems. The influence of geometric parameters on the performance of the printed OECTs is first studied. The geometric optimization study is important for achieving the desired sensitivity and detection limit. Ions and certain molecules can be directly sensed by OECT due to the intrinsic ion sensitivity of channel materials and electrochemical properties of the molecules. Interaction with most analytes and selectivity of biosensors rely on functionalizing the devices with bioreceptors that only respond to the target analyte. Two functionalization approaches, physisorption and chemisorption, are taken to modify the printed OECTs for different sensing applications. </p>

<p>The unfunctionalized printed OECTs are capable of sensing ions and Δ9-THC concentrations in synthetic saliva buffer. These results indicate that 3D printing techniques are suitable for fabricating high-performance OECTs that have sufficient precision for biosensing applications. </p>

<p>Functionalization of aerosol jet printed OECTs with glucose oxidase (GOx) via physisorption for glucose sensing is thoroughly studied. The effects of functionalization sites and nanomaterials are investigated by comparing four configurations: unfunctionalized OECT with floating GOx, GOx functionalized channel, GOx functionalized printed Pt gate, and GOx functionalized sputtered Pt gate. The printed OECT with GOx functionalized printed Pt gate shows the best performance with a detection range between 100 nM to 50 mM and two sensitivities of 0.022NR/dec for 100 nM to 250 μM and 0.255NR/dec for 250 μM to 50 mM. The performance of this sensor is then evaluated in artificial sweat with a detection range of 0.1 to 10 mM, which is well within the human sweat glucose concentration range.</p>

<p>N-heterocyclic carbene (NHC) ligands form extremely stable bonds with metals and have great potential in conjugating organic molecules to metal surfaces. Printed Au electrodes are functionalized with alkyne-modified NHC ligands. The biotin molecules are tethered to the Au electrodes by copper-catalyzed alkyne-azide click chemistry. These modified electrodes are used as gate electrodes for printed OECTs, and streptavidin binding is detected. As the gate functionalization is completely isolated from the device, a variety of processes can be used without damaging the OECT device performance.</p>

<p>Lastly, a point-of-care (POC) COVID-19 diagnostic device is developed. The POC COVID-19 diagnostic device consists of a single-use disposable OECT based biosensor and a custom designed signal processing circuit. Anti-SARS-CoV-2 antibodies are conjugated onto the in-plane gate electrode of the printed OECT. The OECT based biosensor shows selectivity towards SARS-CoV-2 spike proteins with a limit of detection of 1 fg/mL and detects virus-like particles (VLPs) with a sensitivity of -45.7 ± 13.0 mV/dec. The POC diagnostic device is used to test clinical nasopharyngeal samples with an overall accuracy of 87.5%. This is a label-free technique that takes less than 10 minutes to test each sample. This rapid POC diagnostic system could be easily translated to real-world on-site or at home detection device and modified for other applications.</p>

<p>In summary, 3D printing techniques have been employed for fabricating high performance OECTs that are functionalized using different strategies for the detection of glucose, streptavidin, and SARS-CoV-2. These 3D printed OECTs are suitable for different biosensing applications and capable of detecting the analyte in various electrolytes including saliva, sweat, and nasopharyngeal samples. Therefore, this work has demonstrated that there is a bright future for 3D printed OECT based biosensors which will make a significant contribution towards the advancement of precision health.</p>