Synthesis of Molecularly Imprinted Polymer Nanoparticles for SARS-CoV-2 Virus Detection Using Surface Plasmon Resonance

Abstract

COVID-19 caused by a SARS-CoV-2 infection was first reported from Wuhan, China, and later recognized as a pandemic on March 11, 2020, by the World Health Organization (WHO). Gold standard nucleic acid and molecular-based testing have largely satisfied the requirements of early diagnosis and management of this infectious disease; however, these techniques are expensive and not readily available for point-of-care (POC) applications. The COVID-19 pandemic of the 21st century has emphasized that medicine is in dire need of advanced, rapid, and cheap diagnostic tools. Herein, we report on molecularly imprinted polymer nanoparticles (MIP-NPs/nanoMIPs) as plastic antibodies for the specific detection of SARS-CoV-2 by employing a surface plasmon resonance (SPR) sensor. High-affinity MIP-NPs directed against SARS-CoV-2 were manufactured using a solid-phase imprinting method. The MIP-NPs were then characterized using dynamic light scattering (DLS) and atomic force microscopy (AFM) prior to their incorporation into a label-free portable SPR device. Detection of SARS-CoV-2 was studied within a range of 104–106 PFU mL−1. The MIP-NPs demonstrated good binding affinity (KD = 0.12 pM) and selectivity toward SARS-CoV-2. The AFM, cyclic voltammetry, and square-wave voltammetry studies revealed the successful stepwise preparation of the sensor. A cross-reactivity test confirmed the specificity of the sensor. For the first time, this study demonstrates the potential of molecular imprinting technology in conjunction with miniaturized SPR devices for the detection of SARS-CoV-2 particles with high-affinity and specificity. Such sensors could help monitor and manage the risks related to virus contamination and infections also beyond the current pandemic.

Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants

“…Classification of positive and negative swab samples was 95% sensitive and 100% specific (Figure c), including detection of negative oropharyngeal swab samples (from 21 different uninfected volunteers) and positive oropharyngeal swab samples (ranging from 250 to 10,000 TU μL –1 ). The 100% specificity and sensitivity achieved with portable Raman spectrometers (Table S3 and Figure S8) are critical for moving this technique from the laboratory to the field. , …”

“…The 100% specificity and sensitivity achieved with portable Raman spectrometers ( Table S3 and Figure S8 ) are critical for moving this technique from the laboratory to the field. 37 , 38 …”

Real-Time Ellipsometric Surface Plasmon Resonance Sensor Using Polarization Camera May Provide the Ultimate Detection Limit

“…Further, binding kinetics studies were conducted using an excel solver (1) and Origin Pro 8.5. The details of which can be found elsewhere [50].…”

“…For this, adsorption isotherms (Langmuir, Freundlich, and Langmuir-Freundlich) were used and fitted to the relative response of experimental data, as shown in Figure 8d. Langmuir and Langmuir-Freundlich isotherms were fitted using an excel solver from Umpleby et al [52], whereas the Freundlich isotherm was fitted using the alometric1 (classical Freundlich) function from Origin pro 8.5 [50]. All the fitting parameters were calculated from the method mentioned in the above reference to compare and find out the best-fitted model (Table 1).…”

Computationally Designed Epitope-Mediated Imprinted Polymers versus Conventional Epitope Imprints for the Detection of Human Adenovirus in Water and Human Serum Samples

“…These fully synthetic receptors can bind to a specific target with high affinity due to the complementary cavities in the polymer matrix matching the analyte in terms of shape, size, and chemical functionality . A wide range of analytes have been targeted with MIP-based receptors including small molecules like glucose, pharmaceuticals, and endotoxins to large entities such as proteins, viruses, and bacteria . However, imprinting large biosystems is problematic due to the complex and unstable conformational structure leading to the formation of less efficient binding sites .…”