Novel Sensing Algorithm for Linear Read-Out of Bimodal Waveguide Interferometric Biosensors

Abstract

Biosensors employing photonics integrated circuits, and specifically those that rely on interferometric evanescent wave working principles, have outstanding performances due to the extreme sensitivity exhibited in one-step and direct assay, without the need of amplification. Within the interferometric configurations, the Bimodal Waveguide (BiMW) interferometric sensor stands out due to its demonstrated sensitivity for reallife applications and the simplicity of its design. To overcome the ambiguities that arise from the periodic nature of interferometric read-outs, a new all-optical modulation and the subsequent trigonometry-based algorithm have been proposed and applied to the BiMW biosensor. This new algorithm has been successfully employed for the selective identification and quantification of the external Spike (S) protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Our biosensing results from this simple, quick, and user-friendly method demonstrate high sensitivity and specificity and pave the way towards a pointof-care device for general use.

Rapid and direct quantification of the SARS-CoV-2 virus with an ultrasensitive nanobody-based photonic nanosensor

“…Data processing is performed with a customized software interface that incorporates a recently developed optical phase modulation method to transform the complex interferometric signals into a linear signal (Δ φ ), directly proportional to the change of the refractive index occurring at the sensor area which allows real-time monitoring. 20 The sensor chip is integrated with a five-channel polydimethylsiloxane (PDMS) microfluidic system (channel dimensions = 1.25 mm wide × 500 μm height), for continuous flow and washing of the samples. The fluidic system also includes a syringe pump to guarantee a continuous flow rate of a running buffer and a 6-port injection valve connected to a loop (100 μL) that allows the sequential loading and injection of different samples and solutions.…”

“…The BiMW biosensor has previously demonstrated its potential for direct, label-free detection of target biomolecules of different nature, like proteins and small molecules, 20,36,37 DNA and RNA sequences, [38][39][40] and also for the direct capture of bacteria. 24,25 These results set the basis for exploring the use of such a device for the detection of viruses, much smaller entities than bacteria (i.e., around 100 nm diameter compared with considerably larger bacteria, as 1-3 μm).…”

“…, 10 −7 –10 −8 refractive index units, RIU), which is between one and two orders of magnitude better than the benchmarked surface plasmon resonance (SPR) systems. 20 These nanophotonic sensor chips are currently fabricated with well-established microelectronics processes and we have implemented them in biosensor prototypes, demonstrating outstanding performance for the direct analysis of proteins and nucleic acids, with detection limits in the aM range, 21–23 and also for large pathogenic bacteria, achieving direct detection of only a few cells per milliliter ( i.e. , 30–50 CFU mL −1 ).…”

“…19 In fact, the BiMW biosensor stands out among the different label-free photonic sensors due to its extraordinary refractometric resolution (i.e., 10 −7 -10 −8 refractive index units, RIU), which is between one and two orders of magnitude better than the benchmarked surface plasmon resonance (SPR) systems. 20 These nanophotonic sensor chips are currently fabricated with well-established microelectronics processes and we have implemented them in biosensor prototypes, demonstrating outstanding performance for the direct analysis of proteins and nucleic acids, with detection limits in the aM range, [21][22][23] and also for large pathogenic bacteria, achieving direct detection of only a few cells per milliliter (i.e., 30-50 CFU mL −1 ). 24,25 One of the most critical challenges for the direct detection of an emerging and previously unknown virus is the availability of appropriate bioreceptors.…”

High-Performance Bimodal Evanescent-Field Sensor With Coherent Phase Readout

“…The performance of these sensors is substantially dependent on the balanced excitation and the controlled recombination of the two modes, which affects the contrast of the interferogram, and the ability to generate a linear output from the sinusoidal interferometric signal [13]. Conventional modal excitation and recombination relies on abrupt transitions between singlemode and multimode waveguides [14]- [16], see Fig. 1(a).…”