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Optical Biosensors Incubator Meeting

John Goertz

Pros and Cons of Label-free vs. Labeled Optical Biosensors

Before the panel presentations, moderator Marcella Chiari challenged attendees to consider how, despite the many technological advances in optical biosensors, very few have actually found commercial clinical adoption. Furthermore, she introduced the very common, at times heated, debate within the Biosensing community regarding the comparative potential of label-free techniques, which offer high multiplexing and simplicity, yet are plagued by non-specific interactions, versus labeled techniques, which can demonstrate exquisite selectivity and sensitivity at the cost of increased complexity and more difficult multiplexing.

As the first panel began, Marco Buscaglia of the University of Milan discussed progress in low-cost Reflective Phantom Imaging which achieves high sensitivity as well as kinetics analysis and can even be performed with a smartphone. The University of Toronto’s Kagan Kerman then presented methods of using optical LSPR techniques in tandem with electrochemical voltammetric and impedimetric techniques for analysis of Alzheimer’s disease precursors and their interaction with drugs and metal ions. Finally, Brian Cunningham from the University of Illinois gave an industrial perspective on photonic crystals as label-free sensors with particular application to high-throughput pharmacological analysis.

A common point was made regarding the blurring of lines between labeled and label-free technology: label-free techniques offer an excellent platform for assay development which can be ultimately made more specific and sensitive during the final steps of market-specific refinement by the introduction of some labeling method. The subsequent discussion brought to focus key challenges in the adoption of either sensor format. Engineers often focus on an excellent limit-of-detection on as many targets as possible, yet this is ultimately less relevant than clinical accuracy, a setting in which practitioners can often be overwhelmed and hampered by more information than is necessary.

Detecting Single Molecules & their Dynamics with Optical Microcavities

The second keynote presentation was given by Frank Vollmer of the Max Planck Institute. He discussed his work in single-molecule sensing via whispering-gallery mode microsphere resonators. He brought up a central issue of particularly label-free single-molecule detection, namely “How do you know you are detecting exactly one molecule?” His solution was time-domain analysis: by watching analytes repeatedly bind and release from the surface and applying Poisson statistics and kinetic-order analysis for confirmation.

Application of Optical Biosensors to Digital Diagnostics or Single-Molecule Counting

This idea of an orthogonal verification was brought up multiple times during the day, particularly during subsequent presentations by David Freedman with NanoView’s SP-IRIS device and David Duffy with Quanterix’s Simoa platform. These commercial devices utilize analyte morphology and scarcity of reporter molecules, respectively, to achieve the same type of verification.

The panel presentation provided an insightful juxtaposition of three divisions within the field: an academic-focused label-free approach, a commercial labeled approach and a commercial label-free approach. During the discussion, topics such as design considerations and trade-offs, performance optimization and bottlenecks, future directions which require cross-disciplinary input, as well as end-user cost economics offered unique insight into the challenges and thought processes of these incredibly sensitive approaches. Additionally, panelists and attendants alike echoed concern over “overdiagnosis,” or the detection of rare biomarkers which, contrary to previous belief, are not indicative of disease in a binary fashion but rather are often more diagnostically relevant in a differential gradient manner. Ultimately, many concluded that single-molecule counting can further both basic and clinical science synergistically to improve diagnostics, prognostics, and therapeutics.

The Optical Biosensing Incubator continues this afternoon and tomorrow with many more enlightening presentations and insightful discussions on such topics as biosensor commercialization and point-of-care applications.



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