Applications and Innovations of Biosensors in Drug Screening

Biosensors have revolutionized drug screening with their high sensitivity, real-time monitoring, and target-specific recognition. Below, we categorize key examples by technological principles and application scenarios, highlighting breakthroughs from 2020–2025.

I. Fluorescent Biosensors

• iDrugSnFRs (Intensity-based Drug-Sensing Fluorescent Reporters):
  Developed by Caltech, these sensors monitor real-time drug-target interactions via reversible fluorescence signals, enabling subcellular pharmacokinetic studies.
  • Applications:
• Screen CNS drugs (e.g., alkaloids) by tracking drug distribution across organelles and cytoplasm.
• Detect weak-base drugs (<500 Da) in high-throughput screens (44–84 compounds tested per run).
• CY5-ConA Complex:
  Concanavalin A (ConA) conjugated with CY5 dye visualizes drug-glycoprotein interactions.
  • Applications:
• Screen glycosylation-targeting drugs (e.g., tumor surface receptors) to assess binding affinity.
• FRET-based sensors track drug-induced glycoprotein conformational changes.

II. Electrochemical Biosensors

• DNA Interaction Sensors:
  Detect anticancer drug activity via guanine oxidation current changes caused by drug-dsDNA binding.
  • Applications:
• Evaluate cisplatin-DNA crosslinking for anticancer efficacy and toxicity.
• Study dose effects of methotrexate on DNA replication interference.
• Enzyme Inhibition Sensors:
  Immobilized enzymes (e.g., tyrosinase, acetylcholinesterase) detect inhibitor activity.
  • Applications:
• Screen α-glucosidase inhibitors (e.g., acarbose) for diabetes treatment.
• Cytochrome P450 sensors predict drug metabolism and liver toxicity.

III. Optical & SPR Biosensors

• SPR Immunosensors:
  Label-free detection via refractive index shifts from antigen-antibody binding.
  • Applications:
• Measure nitroimidazole drug concentrations (e.g., metronidazole) for antibiotic efficacy.
• Analyze Herceptin-HER2 binding kinetics for targeted cancer drug optimization.
• SERS (Surface-Enhanced Raman Scattering) Sensors:
  Gold/silver nanoparticles amplify Raman signals to single-molecule sensitivity.
  • Applications:
• Screen microtubule stabilizers by detecting paclitaxel-tubulin binding changes.
• Resolve drug-protein complex structures for structure-based drug design (SBDD).

IV. Aptamer & Nanomaterial Biosensors

• Aptamer-Nanochannel Sensors:
  DNA aptamer-modified nanochannels detect drug binding via current changes.
  • Applications:
• Detect cocaine (1 nM–10 μM) for addiction therapy screening.
• Evaluate MDMA analogs for serotonin receptor selectivity.
• Quantum Dot-Biomolecule Sensors:
  CdSe quantum dots coupled with dCas9 enable real-time gene expression tracking.
  • Applications:
• Monitor drug-induced oscillations in gene networks (e.g., p53-MDM2) for epigenetic drug screening.

V. Commercial & Clinical Translation

• Alere™ Toxicology System:
  Multi-channel electrochemical sensor detects 11 drugs (e.g., benzodiazepines, tricyclic antidepressants) for preclinical toxicity assessment.
• Repressilator Circuit Sensors:
  Synthetic gene circuits with metabolite sensors (e.g., arginine) mimic β-cell insulin pulses to screen diabetes drugs.

VI. Future Trends

1. Digital Twins & AI Integration:
   Build dynamic models using single-cell sensor data to predict drug distribution in virtual humans.
2. Wearable Sensors:
   Flexible electrode-microfluidic patches for real-time monitoring in clinical trials.
3. CRISPR-Dynamic Sensors:
   Quantify drug-induced gene editing efficiency via dCas9-fluorescence systems.

Summary
Biosensors are reshaping drug screening through multimodal detection (fluorescence, electrochemical, optical) and nanotechnology integration. Their sensitivity, real-time capabilities, and automation accelerate drug development from target validation to clinical translation. Future integration with single-cell analysis and AI will further advance precision medicine and personalized therapies.

Data sourced from public references. Contact: chuanchuan810@gmail.com.