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PD Dr. Michael Huber

Why did we contact them?

We contacted PD Dr. Michael Huber, Head of Diagnostics & Development at the Institute of Medical Virology, University of Zurich, because we wanted to get his expert opinion on our approach and learn from his experience with diagnostics. Our objective was to better understand the workflow of diagnostic test development, get feedback on amplification and detection methods, and receive advice on potential collaborators.

Discussion

Pathogen-specific questions

Dr. Huber explained that his group mainly works with pathogens such as HIV and does not have direct experience with HPV. Since we are working with DNA extracts, he highlighted that the workflow does not differ much between bacterial and viral pathogens. For pathogen-specific expertise, he referred us to the Institute of Pathology and Molecular Pathology at USZ and also suggested contacting experts in Medical Microbiology (Oliver Nolte and Frank Imkamp).

Amplification, detection, lysis and freeze-drying

Dr. Huber shared that their diagnostics relies mainly on real-time qPCR and antigen testing, and that he does not have experience with RPA or freeze-drying. He suggested that we consult the Institute of Biochemistry regarding freeze-drying. He also mentioned that Veterinary Virology had worked with LAMP in the past and could be worth checking.

Workflow of diagnostic test development

Dr. Huber outlined a possible workflow for developing a diagnostic test:

  1. Choose detection sequences (from literature in our case).
  2. Find and test the right primers using synthetic controls.
  3. Test detection with dilution series.
  4. Test with patient samples to check for inhibitors.
  5. Use a housekeeping gene as proof of concept before moving to pathogen detection.
  6. Compare results to conventional diagnostics such as qPCR.

He recommended prioritizing proof of concept in this order:

  1. Amplification with synthetic DNA and established primer systems, verified by qPCR.
  2. Detection.
  3. Compatibility with real sample types (urine, lysis).

Considerations for diagnostics

Dr. Huber discussed challenges of diagnostic development:

  • Screening tests may give false positives, requiring confirmation by a laboratory test.
  • Health insurance does not cover such tests, making cost an important factor.
  • Regulatory hurdles, as seen in the case of HIV and Hepatitis C tests. For example, AIDS Hilfe Schweiz had to stop distributing an at-home test because swabs were not approved for use by nonprofessionals.
  • He advised us to consider whether we should develop a point-of-care test instead of a self-test, if lysis or isothermal amplification proves difficult. The main advantages would still be speed and possibly reduced costs.

Main Takeaways

  • He provided a clear workflow outline for diagnostic development.
  • He emphasized starting with proof of concept
  • He suggested other experts and institutes to contact (Microbiology, Pathology, Biochemistry).
  • He highlighted important considerations for costs, regulations, and the potential focus on point-of-care instead of self-testing.

Integration

We integrated Dr. Huber’s advice by:

  • Contacting other suggested experts and institutes for pathogen-specific knowledge and freeze-drying expertise.
  • Reviewing the workflow he proposed and adopting it as a guideline for our proof of concept experiments.
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