Label-free detection of nanoparticles and biological molecules using microtoroid optical resonators
View Patent ↗Systems and methods are provided for detecting one or more particles such as individual unlabeled molecules or single nanoparticles. In examples described herein, optical energy is introduced into a microtoroid or other microcavity to generate an evanescent field. The microcavity has a functionalized outer surface that has been functionalized with a chemically or biologically active substance such as an antibody, antigen or protein. An indication of a particle bound to the functionalized outer surface of the microcavity is then detected based on a reactive interaction between the particle and the evanescent field while using frequency locking, balanced detection and various filtering techniques. The frequency locking, balanced detection and filtering techniques reduce the signal-to-noise ratio (SNR) of the detection system so that single nanoparticles (e.g. 2.5 nanometers (nm) in radius) and individual molecules (e.g. 15.5 kilo-Dalton (kDa) in size) can be detected in aqueous solution in some examples.
1. A method for particle detection, comprising:
introducing electromagnetic energy into a microcavity to generate an evanescent field extending beyond an outer surface of the microcavity; and
detecting an indication of a particle bound to the outer surface of the microcavity based on a reactive interaction between the particle and the evanescent field using frequency locking and balanced detection.
2. The method of claim 1 wherein the particle comprises a plurality of unlabeled molecules.
3. The method of claim 1 wherein the particle is a single unlabeled molecule.
4. The method of claim 1 wherein the particle comprises one or more nanoparticles.
5. The method of claim 1 wherein the electromagnetic energy comprises optical energy received from a coherent light source.
6. The method of claim 5 wherein introducing energy comprises coupling optical energy into the microcavity from a waveguide to circulate optical energy inside the microcavity to generate an evanescent field of sufficient strength to react with one or more of the particles to cause a detectable shift in a wavelength of optical energy resonating in the microcavity.
7. The method of claim 6 further comprises splitting optical energy from the coherent light source onto first and second waveguide arms to couple a first portion of the optical energy into the microcavity using the first arm of the waveguide while routing a second portion of the optical energy along the second arm of the waveguide without microcavity coupling.
8. The method of claim 7 further comprising a balanced receiver to receive optical energy along the first and second arms of the waveguide wherein detecting an indication of a particle using balanced detection comprises generating a balanced difference signal using the balanced receiver wherein the difference signal is representative of a peak resonance wavelength associated with one or more particles.
9. The method of claim 8 further comprising frequency-locking system to receive an output of the balanced receiver wherein detecting an indication of a particle using frequency locking comprises locking a frequency of the coherent light source to a frequency corresponding to the peak resonance wavelength associated with one or more of the particles.
10. The method of claim 6 wherein the waveguide comprises an optical fiber coupled directly to the microcavity to provide over-coupling.
11. The method of claim 1 wherein detecting an indication of a particle based on the reactive interaction between the particle and the evanescent field using frequency locking and balanced detection improves a signal-to-noise ratio associated with the detection.
12. The method of claim 1 wherein detecting an indication of the particle based on the reactive interaction between the particle and the evanescent field further employs digital filtering including one or more of Fourier filtering and median filtering.
13. The method of claim 1 wherein the microcavity is a microtoroid.
14. The method of claim 13 wherein the microtoroid is planar and formed of silica.
15. The method of claim 1 , wherein the microcavity is immersed in an aqueous environment during detection of the indication of the particle.
16. The method of claim 1 , wherein the microcavity has a Q value sufficient to allow detection of individual unlabeled molecules bound to the outer surface based on a wavelength shift of optical energy resonating in the microcavity.
17. The method of claim 16 , wherein the microcavity has a Q value less than 10 6 .
18. The method of claim 1 , wherein the outer surface is functionalized with one or more of a chemically active substance, a biologically active substance, an antibody, an antigen and a protein.
19. A system for particle detection, comprising:
an input system operative to introduce electromagnetic energy into a microcavity to generate an evanescent field extending beyond an outer surface of the microcavity; and
a frequency-locked and balanced detector operative to detect an indication of a particle bound to the outer surface of the microcavity based on a reactive interaction between the particle and the evanescent field using frequency locking and balanced detection.
20. A method for unlabeled molecule detection, comprising:
introducing electromagnetic energy into a microcavity to generate an evanescent field extending beyond an outer surface of the microcavity; and
detecting an indication of an unlabeled molecule bound to the outer surface of the microcavity based on a shift in wavelength of the electromagnetic energy resonating in the microcavity due to a change in effective path length in a reactive interaction between the unlabeled molecule and the evanescent field that is independent of the optical power of the electromagnetic energy.