Whispering gallery mode biosensor: Fulfilling the promise of single virus detection without labels

None of civilization's socio-political catastrophes (e.g. world wars) have caused an equivalent destructive effect on the world's population as biological pandemics [1]. Exponentially growing pathogens are difficult to contain and eliminate unless they can be detected early on. Some years ago, one of us (S.A.) reflected on this problem as a friend was dying from a viral infection. His friend's diagnosis came too late; real-time methods for testing for the virus were not available. Fast and early detection on site of an outbreak requires biosensors where ideally individual viral particles produce a quantitative signal. A decision was made to direct the MicroParticle PhotoPhysics Lab toward finding a solution. Our approach was to sense bio-particles using the high sensitivity afforded by the perturbation that an adsorbed molecule has on high Q (10₇) optical resonances of a microparticle [2]. In particular, bio-particle adsorption was sensed from the associated shift in resonance frequency [3, 4]. Through all the eons of evolution, nature has evolved bio-nano-probes that specifically grab onto protein, DNA and foreign invaders through physio-chemical interactions. Following nature, our approach was to use these bio-nano-probes as surface-bound recognition elements and the microparticle to transduce (report) the interaction [5]. We seek to identify the whole virus by tranducing the immobilization that takes place when a coat protein on its surface interacts with a complementary antibody anchored to the microparticle surface. We set a goal to record binding steps of individual virions that can exceed the experimental noise level [6]. Although field effect techniques using nano-fibers have demonstrated single virion sensing in the past [7], reactive Whispering Gallery Mode (WGM) biosensing adds a new dimensions to what can be learned: the measured wavelength shift enables one to identify the virion size and mass. In the process of working on single particle detection we discovered that light confined in a WGM can manipulate a nanoparticle's motion and substantially enhance the rate at which these particles are sensed. This effect dimensionally reduces the transport process by forming a carousel of particles that "hunt" for anti-bodies where the sensitivity is greatest (WGM Carousel) [8].