Key Considerations for Diagnostic Development

  • Integration with existing diagnostic techniques
  • Sensitivity and specificity of tests
  • Validation against gold standard methods
  • Multiplexing capabilities
  • Sample amount and processing time
  • Cost and complexity of testing
  • Sample source and readout techniques

Encephalitis Example

  • Decision Tree Placement: Important to determine where a new test fits within the diagnosis hierarchy.
  • Differential Diagnoses: Many conditions, especially autoimmune diseases, may present similarly; distinguishing features are crucial.
  • Reference: Graus, Francesc et al. (2016). A clinical approach to diagnosis of autoimmune encephalitis. The Lancet Neurology, 15(4), 391-404.
  • Physician Judgment: Decisions based on symptoms due to the high costs and lengthy turnaround times of diagnostic tests.
  • Integrative Approach: A new test should define its role in relation to existing diagnostic methods.
  • Autoantibodies: Characterization of autoimmunity often involves measuring autoantibodies; research focuses on innovative identification techniques.

Asthma Example

  • Patient Compliance: Issues with test adherence particularly among children and elderly populations.
  • Misdiagnosis Risks: Subpopulations such as obese patients might not reflect typical disease severity.
  • Reference: Sackmann, Eric Karl-Heinz et al. (2014). Characterizing asthma from a drop of blood using neutrophil chemotaxis. Proceedings of the National Academy of Sciences, 111(16), 5813-5818.
  • Neutrophil Chemotaxis:
  • Purification of neutrophils
  • Application of chemokines for testing chemotactic ability (speed, index)
  • Automation of tracking analysis for efficient data collection
  • Comparison with Gold Standards: Important to establish optimal specificity/sensitivity cut-off for the biomarkers in use.

Microfluidics

  • Innovation in Diagnostics: Microfluidic systems improve reagent and sample efficiency, sensitivity, and integration of processes.
  • Example: Eamer, Lise et al. (2015). Microfluidic assessment in sperm selection. Biomicrofluidics, 9(4), 044113.
  • Challenges: Reliability of external components (e.g., syringe pumps), manufacturing complexities, and sample preparation requirements.
  • Advantages: Reduced processing time and resource consumption.

Allergy Example

  • Limitations of Current Tests:
  • Skin prick tests may not accurately predict reactions due to differences in immune system responses or unrelated skin conditions.
  • Serum IgE tests may not correlate with disease severity, especially post-immunotherapy.
  • Nanostructured Biosensors:
  • Recent innovations allow for miniaturization of assays requiring only small serum samples (25 μL).
  • Faster detection times (<1 minute) with improved multiplexing potential.
  • Challenges include scalability and robust correlation with traditional methods.
  • Microfluidics in Allergy Testing:
  • Simplified infrastructure requirement with rapid assay time and high throughput potential.
  • Reference: Chinnasamy, Thiruppathiraja et al. (2014). Point-of-care allergen microarray assay. Clinical Chemistry, 60(9), 1209-1216.
  • Synthetic Biology Solutions: New methods employing synthetic biology can enhance allergic reaction testing efficiency.
  • Pros: High throughput and sensitivity; ability to test multiple allergen concentrations.
  • Cons: Stability and lifespan of cell lines; cost and time-intensive handling (approximately 36 hours).
  • Reference: Ausländer, David et al. (2014). Designer cell-based histamine-specific allergy profiler. Nature Communications, 5, 4408.
  • Emerging Portable Testing: Development of portable devices for real-time food allergen detection (e.g., gluten and peanut sensors).