Advances and challenges in biosensor-based diagnosis of infectious diseases

Abstract

Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings.

Keywords::

• biosensor
• infectious diseases
• matrix effects
• microfluidics
• sample preparation
• system integration

Financial & competing interests disclosure

JC Liao and PK Wong were supported by NIH/NIAID grant U01 AI082457. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Current in vitro diagnostics require centralized laboratory, experienced personnel and large expensive equipment.

• Timely diagnosis and initiation of targeted antimicrobial treatment with portable, sensitive, specific and cost-effective biosensor technologies are keys to clinical management in decentralized and resource-poor settings.

• Label-free assays may allow quantitative real-time measurement, yet suffer from a significant degree of non-specific bindings and aberrant signals with analytes in complex matrices.

• In labeled assays, incorporation of multiple binding events and amplification tags increase specificity and sensitivity, yet multistep protocols increase the assay complexity.

• Matrix effects of clinical samples present a common problem for biosensor technologies and biosensors demonstrating promising performance with original clinical samples are rare.

• Developing chip-based sample preparation strategies in microfluidic systems for enrichment of target analytes, removal of matrix inhibitors and sample volume reduction is essential for translating biosensors from laboratory to clinic.

• System integration of three major modules of a biosensor, which are detection mechanism, microfluidics-based sample preparation strategies and a transducer, into a fully automated and standalone platform remains the most critical challenge for point-of-care device commercialization.

Notes