Optofluidic wavelength division multiplexing for single-virus detection

Abstract

Optical waveguides simultaneously transport light at different colors, forming the basis of fiber-optic telecommunication networks that shuttle data in dozens of spectrally separated channels. Here, we reimagine this wavelength division multiplexing (WDM) paradigm in a novel context––the differentiated detection and identification of single influenza viruses on a chip. We use a single multimode interference (MMI) waveguide to create wavelength-dependent spot patterns across the entire visible spectrum and enable multiplexed single biomolecule detection on an optofluidic chip. Each target is identified by its time-dependent fluorescence signal without the need for spectral demultiplexing upon detection. We demonstrate detection of individual fluorescently labeled virus particles of three influenza A subtypes in two implementations: labeling of each virus using three different colors and two-color combinatorial labeling. By extending combinatorial multiplexing to three or more colors, MMI-based WDM provides the multiplexing power required for differentiated clinical tests and the growing field of personalized medicine.

Single-Virus Analysis Through Chip-Based Optical Detection

“…Single-virus analysis through chip-based optical detection Commentary were recently shown to enable a new multiplexing technique based on wavelength division multiplexing [13]. By using a multimode interferometer waveguide section to intersect the fluidic channel, color-dependent spatial excitation patterns are generated that lead to multipeak signals in the time domain as a fluorescent target flows past this excitation region.…”

Sequence-specific DNA solid-phase extraction in an on-chip monolith: Towards detection of antibiotic resistance genes

“…Improved recovery could be achieved by using a longer monolithic column, but that would increase backpressure and elution volume, which would not work well for our intended analysis. The 100 μL of 1 pM sample corresponded to 60 million target copies loaded; much lower copy numbers could be detected by integrating our extraction module with a single-molecule counting setup [39]. …”

“…Integrating monolithic column sequence-specific capture of targeted genes with a device with modules for separation and lysis of bacteria from blood [40], followed by single-molecule fluorescence detection on an optofluidic platform [39], should allow rapid determination of antibiotic resistance in patients. Such a device, currently under development in an instrument that includes a pumping mechanism, is expected to allow detection of genes related to antibiotic resistance in approximately one hour, compared to commonly used methods that currently take 24–72 hours.…”

Optofluidic devices with integrated solid-state nanopores

“…[75] A wide solid-core waveguide, acting as a single multimode interference (MMI) waveguide creates wavelength-dependent spot patterns along the intersecting liquid-core waveguide. When particles pass the spots, a series of fluorescence spikes can be detected.…”