NanoMIP based biomimetic receptors for virus detection and removal using integrated approaches

• Applicant: Professorin Dr. Zeynep Altintas
• Subject Area: Analytical Chemistry ; Biological and Biomimetic Chemistry
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 428780268

• Final Report Year: 2025

Final Report Abstract

Viruses are one of the most common contaminants found in water and can be infectious even at trace amounts since they are highly stable and persistent even in harsh environmental conditions. The detection of viruses in water requires specialized analytical methods and trained personnel limits their point-of care applicability. On the other hand, existing virus diagnostic methods lack the sensitivity needed to ensure the complete absence of waterborne viruses in water sources. In this project, we aimed to address this challenge by developing biomimetic receptors (nanoMIPs) for the detection and capturing of viruses. The developed virusspecific nanoMIPs were integrated into biosensing platforms and membrane filters for virus detection and removal applications. We successfully integrated computational simulations with experimental work to optimize the performance of nanoMIPs for virus recognition and filtration. In order to obtain efficient receptors with high affinity towards target viruses, we performed molecular dynamics simulations of viral surface proteins to assess the stability and conformational dynamics of the epitopes (i.e. binding sites) under various environmental conditions. In addition to epitope selection, computational simulations were also utilized to design MIP-based receptors. For this, different candidate functional monomers were simulated with the selected epitope to monitor the binding interactions and the nature of bonds. Accordingly, the monomers showing the most optimum interactions were utilized in the subsequent synthesis of the nanoMIPs as receptors for the specific epitopes via molecular imprinting technique. The synthesized biomimetic receptors were then employed to fabricate biosensing chips by covalent immobilization. These chips were integrated into piezoelectrical and optical biosensors, allowing for the detection of whole viruses through their epitope regions. The interaction between each epitope receptor and the target virus was analyzed based on biosensor outputs. High-affinity biomimetic receptors were further incorporated into membrane filters to effectively capture and remove viral particles. The development of these nanoMIP-based sensors serves as rapid, accurate, and accessible point-of-care diagnostic tools. Furthermore, the nanoMIP-conjugated membrane filters can potentially have a transformative impact, particularly in resource-limited regions. Further details on developed nanoMIP-based sensing units and membranes are given in the following sections.

Publications

• Bioselective PES Membranes Based on Chitosan Functionalization and Virus-Imprinted NanoMIPs for Highly Efficient Separation of Human Pathogenic Viruses from Water. Membranes, 12(11), 1117.
  Olivares Moreno, Carmen Andreina & Altintas, Zeynep
  
• Current trends in COVID-19 diagnosis and its new variants in physiological fluids: Surface antigens, antibodies, nucleic acids, and RNA sequencing. TrAC Trends in Analytical Chemistry, 157, 116750.
  Mostafa, Menna; Barhoum, Ahmed; Sehit, Ekin; Gewaid, Hossam; Mostafa, Eslam; Omran, Mohamed M.; Abdalla, Mohga S.; Abdel-Haleem, Fatehy M.; Altintas, Zeynep & Forster, Robert J.
  
• Synthesis of Molecularly Imprinted Polymer Nanoparticles for SARS-CoV-2 Virus Detection Using Surface Plasmon Resonance. Chemosensors, 10(11), 459.
  Bajaj, Aabha; Trimpert, Jakob; Abdulhalim, Ibrahim & Altintas, Zeynep
  
• Biosensors for virus detection. Advanced Sensor Technology, 53-80. Elsevier.
  Sehit, Ekin & Altintas, Zeynep
  
• Chitosan-functionalized PVDF and PES membranes integrated by epitope-imprinted polymers for targeted hepatitis A virus capture. Journal of Membrane Science, 709, 123084.
  Akin, Eda; Gharibzahedi, Seyed Mohammad Taghi; Qiu, Haoyi; Aliyeva, Ainura & Altintas, Zeynep
  
• Computationally Designed Epitope-Mediated Imprinted Polymers versus Conventional Epitope Imprints for the Detection of Human Adenovirus in Water and Human Serum Samples. ACS Sensors, 9(4), 1831-1841.
  Sehit, Ekin; Yao, Guiyang; Battocchio, Giovanni; Radfar, Rahil; Trimpert, Jakob; Mroginski, Maria A.; Süssmuth, Roderich & Altintas, Zeynep
  
• Surface modification of PVDF ultrafiltration membranes using spacer arms and synthetic receptors for virus capturing and separation. Talanta, 279, 126558.
  Olivares Moreno, Carmen Andreina; Ghaddar, Nabila; Sehit, Ekin; Schomäcker, Reinhard & Altintas, Zeynep
  
• Molecularly Imprinted Polymers. Springer Series on Polymer and Composite Materials. Springer International Publishing.
  Altintas, Zeynep