The seasonal outbreaks of infectious respiratory viruses can impose a heavy burden on public health care. Therefore, developing fast, accurate, and low-cost tools to diagnose whether infected with infectious respiratory viruses has always been one of the priorities for epidemic prevention and control. As a simple and cheap material, hydrogel has great application prospects in this field.
In order to realize rapid and sensitive immune sensing of virus aerosol, Professor Liu Qingjun's team of Zhejiang University creatively developed an immune response hydrogel modulated resonance (ImmHR) sensor. The immune response hydrogel used in the sensor is mainly composed of polyacrylamide (AAm) network and antibody modified gold nanoparticles (AuNPs Ab).The author used SARS-CoV-2, H1N1 influenza, and RSV as examples to verify the high sensitivity and accuracy of the device, providing a simple, accurate, and universal platform for biosensing and diagnosis of infectious respiratory diseases.
[The Structure and Mechanism of Wireless Immunoassay Technology]
The wireless immune analysis platform developed by the author consists of ImmHR sensors and RF readout coils. In order to detect various samples (saliva, aerosol, etc.) from the respiratory tract, the sensor couples the immune response hydrogel and a pair of radio frequency resonators to form a resonant structure that can be tuned during the immune response, and converts the stimulus response of the target antigen into the change of resonant frequency. In addition, competitive antigen binding further led to the aggregation of AuNPs, which made the blue hydrogel fade gradually, so it was suitable for colorimetric determination.
[Hydrogel formation and composition optimization]
The authors used SARS CoV-2 nucleocapsid protein (NP) and corresponding antibodies as model antigens and antibodies to prepare immune response hydrogels. Due to the destruction of immune cross-linking, the further competitive immune binding between the viral antigen and AuNPs Ab triggered strong hydrogel swelling.In addition, obvious color signals can be measured within 5~10 minutes by the colorimetric determination of the viral antigen on the hydrogel. Meanwhile, the author uses medical grade atomizers for production
[ImmHR sensor wireless aerosol detection]
Since the thickness of the hydrogel dielectric layer can modulated the resonance frequency deviation (ΔFres), the coupling between the sensor and the readout coil is further studied by using the intermediate coil (IR), so as to reduce the influence of the relative displacement of the readout coil on the results.By fitting the response of the sensor to the viral antigen protein aerosol with gradient concentration, the calculated detection limit of the sensor is low fg/L or even sub-FG /L, thus realizing the ultra-sensitive detection of viral aerosol. In addition, the ImmHR sensor can also be compatible with temperature-responsive hydrogels to build physical sensors, so as to detect parameters such as exhaled air temperature.
[Wearable integration and multi-channel readout]
ImmHR sensors have advantages such as fast detection speed, high sensitivity, complete wireless, and no battery configuration. Therefore, miniaturized and lightweight ImmHR sensor arrays can be fixed on parallel intermediate coils and adhered to the surface of masks for wearable aerosol detection. The configuration of this wearable sensor is wirelessly coupled with a shared detector (connected to the reading coil of the vector network analyzer) and can be widely used for on-site immune diagnosis, such as community infection monitoring at the entrance to the workplace.
【Clinical sample testing using wireless immunoassay method】
To evaluate the feasibility of using ImmHR based wireless immunoassay technology for clinical sample detection, the authors collected nasopharyngeal swabs and saliva samples from 40 patients and 20 healthy volunteers. The statistical results further demonstrate that there is a significant difference in the signal generated by the sensor for H1N1 positive and negative samples, demonstrating the potential of this method for diagnosing viral infections.Compared with recent advances in rapid and sensitive immunoassays reported, wireless immunoassays based on ImmHR sensor have the advantages of rapid detection, high sensitivity, convenient device configuration, and compatible wearable integration.
Summary: The authors demonstrate a wireless immunoassay technique to detect SARS-CoV-2, H1N1, and RSV virus antigens in aerosols by replacing antigen/antibody recognition elements with response times of about 10 minutes.Therefore, wireless immunoassay technology can not only serve as a versatile immune sensing platform to capture and quantify viral protein biomarkers, but also detect other important but low-abundance protein biomarkers in various biological fluids (inflammatory biomarkers in sweat, cytokines in wound exudate or interstitial fluid, and exosomes in plasma, among others).In addition, from a rich variety of polymers and biometric components (adaptors, DNA, Or CRISPR tool), which can also include metabolites and nucleic acids in detectable analytes.In addition, combining different types of biometric elements into a set of ImmHR sensors or distributing them spatially within a sensor is expected to greatly improve the accuracy of biomarker detection and disease diagnosis (infectious diseases and cancer, etc.).
Source: Sensor Expert Network