Optofluidic analyte detection systems using multi-mode interference waveguides

Abstract

Systems, methods, and techniques for optofluidic analyte detection and analysis using multi-mode interference (MMI) waveguides are disclosed herein. In some embodiments, spatially and spectrally multiplexed optical detection of particles is implemented on an optofluidic platform comprising multiple analyte channels intersecting a single MMI waveguide. In some embodiments, multi-stage photonic structures including a first stage MMI waveguide for demultiplexing optical signals by spatially separating different wavelengths of light from one another may be implemented. In some embodiments, a second stage may use single-mode waveguides and/or MMI waveguides to create multi-spot patterns using the demultiplexed, spatially separated light output from the first stage. In some embodiments, liquid-core MMI (LC-MMI) waveguides that are tunable by replacing a liquid core, heating/cooling the liquid core, and/or deforming the LC-MMI to change its width may be implemented in one or more of the analyte detection/analysis systems disclosed herein.

1 . A system for on-chip analyte detection, comprising:
 a substrate;   a first analyte channel, disposed on the substrate, configured to receive a first liquid containing first analytes to be detected by the system;   a second analyte channel, disposed on the substrate, configured to receive a second liquid containing second analytes to be detected by the system;   a multi-mode interference (MIMI) waveguide, disposed on the substrate, that intersects the first analyte channel at a first position and the second analyte channel at a second position, wherein the MMI waveguide is configured to:
 receive input light of a first wavelength and input light of a second wavelength; 
 generate a first spot pattern having a first number of spots of light of the first wavelength incident on the first analyte channel; 
 generate a second spot pattern having a second number of spots of light of the first wavelength incident on the second analyte channel; 
 generate a third spot pattern having a third number of spots of light of the second wavelength incident on the first analyte channel; and 
 generate a fourth spot pattern having a fourth number of spots of light of the second wavelength incident on the second analyte channel; 
   a detector configured to detect fluorescence bursts from an analyte excited by one of the first spot pattern, the second spot pattern, the third spot pattern, and the fourth spot pattern; and   one or more processors configured to:
 receive a signal from the detector representing the detected fluorescence bursts; 
 determine, based on a detected number of bursts in the received signal, whether the signal corresponds to the first channel or to the second channel; and 
 determine, based on the detected number of bursts in the received signal, whether the signal corresponds to the first wavelength of light or to the second wavelength of light. 
   
     
     
         2 . The system for on-chip analyte detection of  claim 1 , wherein the processor is further configured to determine, based on the detected number of bursts in the received signal, an identity of the analyte. 
     
     
         3 . The system for on-chip analyte detection of  claim 1 , wherein the first analyte channel and the second analyte channel are each a waveguide configured to guide light of fluorescence bursts toward the detector. 
     
     
         4 . The system for on-chip analyte detection of  claim 1 , wherein the detector is disposed on the chip and configured to receive light guided from the analyte channels in a same plane as the analyte channels. 
     
     
         5 . The system for on-chip analyte detection  claim 1 , wherein:
 the first position is located a first distance from an optical input port of the MMI waveguide such that the light of the first wavelength forms the first number of spots at the first position and the light of the second wavelength forms the third number of spots at the first position; and   wherein the second position is located a second distance from the optical input port of the MMI waveguide such that the light of the first wavelength forms the second number of spots at the second position and the light of the second wavelength forms the fourth number of spots at the fourth position.   
     
     
         6 . The system for on-chip analyte detection of  claim 1 , wherein:
 a height of the MMI waveguide is less than or equal to: 0.1 μm, 0.5 μm, 1 μm, 2 μm, or 5 μm; and   a width of the MMI waveguide is less than or equal to: 10 μm, 25 μm, 50 μm, 100 μm, or 250 μm.   
     
     
         7 . The system for on-chip analyte detection of  claim 1 , wherein:
 a height of the first analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm, or 10 μm; and   a width of the first analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm, 10 μm, or 20 μm.   
     
     
         8 . The system for on-chip analyte detection of  claim 1 , wherein:
 a width of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm; and   a length of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm.   
     
     
         9 . A system for on-chip analyte detection, comprising:
 a substrate;   an analyte channel, disposed on the substrate, configured to receive a liquid containing analytes to be detected by the system;   one or more first waveguides, disposed on the substrate, that intersect the analyte channel, wherein the one or more first waveguides are configured to receive input light of a first wavelength at a first input port and to direct a first multi-spot pattern generated from the input light of the first wavelength onto the intersecting analyte channel;   one or more second waveguides, disposed on the substrate, that intersect the analyte channel, wherein the one or more second waveguides are configured to receive input light of a second wavelength at a second input port and to direct a second multi-spot pattern generated from the input light of the second wavelength onto the intersecting analyte channel; and   a demultiplexing multi-mode interference (MMI) waveguide, disposed on the substrate, the demultiplexing MMI waveguide comprising:
 a third input port, disposed at a first end of the demultiplexing MMI waveguide, configured to receive input light of the first wavelength and input light of the second wavelength; 
 a first output port, disposed at a second end of the demultiplexing MMI waveguide opposite the first end, wherein light of the first wavelength is directed to the first input port of the first set of one or more waveguides; and 
 a second output port, disposed at the second end of the demultiplexing MMI waveguide, configured to output a mirror-image of light of the second wavelength, wherein light of the second wavelength is directed to the second input port of the second set of one or more waveguides. 
   
     
     
         10 . The system for on-chip analyte detection of  claim 9 , wherein the third input port is off-center from a center of the demultiplexing MMI waveguide in a first direction perpendicular to the direction of propagation of light in the demultiplexing MMI waveguide. 
     
     
         11 . The system for on-chip analyte detection of  claim 10 , wherein:
 the first output port is off-center from the center of the demultiplexing MMI waveguide in the first direction, configured to output a self-image of light of the first wavelength; and   the second output port is off-center from the center of the demultiplexing MMI waveguide in a second direction opposite the first direction.   
     
     
         12 . The system for on-chip analyte detection of  claim 9 , wherein the first set of one or more waveguides comprises a first analyte-excitation MMI waveguide configured to generate the first multi-spot pattern by multi-mode interference. 
     
     
         13 . The system for on-chip analyte detection of  claim 9 , wherein the second set of one or more waveguides comprises a second analyte-excitation MMI waveguide configured to generate the second multi-spot pattern by multi-mode interference. 
     
     
         14 . The system for on-chip analyte detection of  claim 9 , wherein the first set of one or more waveguides comprises one or more single-mode waveguides. 
     
     
         15 . The system for on-chip analyte detection of  claim 9 , wherein the second set of one or more waveguides comprises one or more single-mode waveguides. 
     
     
         16 . The system for on-chip analyte detection of  claim 9 , further comprising a detector configured to detect fluorescence bursts from an analyte excited by one or both of the light of the first wavelength and the light of the second wavelength. 
     
     
         17 . The system for on-chip analyte detection of  claim 9 , wherein:
 a height of the demultiplexing MMI waveguide is less than or equal to: 0.1 μm, 0.5 μm, 1 μm, 2 μm, or 5 μm; and   a width of the demultiplexing MMI waveguide is less than or equal to: 10 μm, 25 μm, 50 μm, 100 μm, or 250 μm.   
     
     
         18 . The system for on-chip analyte detection of  claim 10 , wherein an offset distance by which the third input port is off-center is greater than or equal to: 10%, 25%, or 45% of a width of the demultiplexing MMI waveguide. 
     
     
         19 . The system for on-chip analyte detection of  claim 9 , wherein:
 a height of the analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm, or 10 μm; and   a width of the analyte channel is less than or equal to: 1 μm, 2 μm, 5 ∞m, 10 μm, or 20 μm.   
     
     
         20 . The system for on-chip analyte detection of  claim 9 , wherein:
 a width of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm; and   a length of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm.   
     
     
         21 . A system for on-chip analyte detection, comprising:
 a substrate;   an analyte channel, disposed on the substrate, configured to receive a liquid containing analytes to be detected by the system; and   a demultiplexing multi-mode interference (MMI) waveguide, disposed on the substrate, the demultiplexing MMI waveguide comprising:
 a first input port, disposed at a first end of the demultiplexing MMI waveguide, configured to receive input light of a first wavelength and input light of a second wavelength; 
 a first output port, disposed at a second end of the demultiplexing MMI waveguide opposite the first end of the demultiplexing MMI waveguide, configured to output light of the first wavelength; and 
 a second output port, disposed at the second end of the demultiplexing MMI waveguide, configured to output light of the second wavelength; 
   wherein the demultiplexing MMI waveguide is configured to direct output light of the first wavelength and output light of the second wavelength to be incident on the analyte channel to excite one or more analytes in the channel.   
     
     
         22 . The system for on-chip analyte detection of  claim 21 , wherein the first input port is off-center from a center of the demultiplexing MMI waveguide in a first direction perpendicular to a direction of propagation of light in the demultiplexing MMI waveguide. 
     
     
         23 . The system for on-chip analyte detection of  claim 22 , wherein:
 the first output port is off-center from the center of the demultiplexing MMI waveguide in the first direction and configured to output a self-image of light of the first wavelength; and   the second output port is off-center from the center of the demultiplexing MMI waveguide in a second direction opposite the first direction and configured to output a mirror-image of light of the second wavelength   
     
     
         24 . The system for on-chip analyte detection of  claim 21 , further comprising a detector configured to detect fluorescence bursts from an analyte excited by one or both of the output light of the first wavelength and the output light of the second wavelength. 
     
     
         25 . The system for on-chip analyte detection of  claim 21 , further comprising a detector configured to detect fluorescence bursts from an analyte excited by one or both of the light of the first wavelength and the light of the second wavelength. 
     
     
         26 . The system for on-chip analyte detection of  claim 21 , wherein:
 a height of the demultiplexing MMI waveguide is less than or equal to: 0.1 μm, 0.5 μm, 1 μm, 2 μm, or 5 μm; and   a width of the demultiplexing MMI waveguide is less than or equal to: 10 μm, 25 μm, 50 μm, 100 μm, or 250 μm.   
     
     
         27 . The system for on-chip analyte detection of  claim 22 , wherein an offset distance by which the first input port is off-center is greater than or equal to: 10%, 25%, or 45% of a width of the demultiplexing MMI waveguide. 
     
     
         28 . The system for on-chip analyte detection of  claim 21 , wherein:
 a height of the analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm, or 10 μm; and   a width of the analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm, 10 μm, or 20 μm.   
     
     
         29 . The system for on-chip analyte detection of  claim 21 , wherein:
 a width of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm; and   a length of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm.   
     
     
         30 . A system for on-chip analyte detection, comprising:
 a substrate;   an analyte channel, disposed on the substrate, configured to receive a liquid containing analytes to be detected by the system; and   a multiplexing multi-mode interference (MMI) waveguide, disposed on the substrate, the demultiplexing MMI waveguide comprising:
 a first input port, disposed at a first end of the multiplexing MMI waveguide, configured to receive light of a first wavelength; 
 a second input port, disposed at the first end of the multiplexing MMI waveguide, configured to receive light of a second wavelength; and 
 an output port, disposed at a second end of the multiplexing MMI waveguide opposite the first end of the multiplexing MMI waveguide, configured to output light of the first wavelength and light of light of the second wavelength; 
   wherein the multiplexing MMI waveguide is configured to direct output light of the first wavelength and output light of the second wavelength to be incident on the analyte channel to excite one or more analytes in the channel.   
     
     
         31 . The system for on-chip analyte detection of  claim 30 , wherein:
 the first input port is off-center from a center of the multiplexing MMI waveguide in a first direction perpendicular to a direction of propagation of light in the multiplexing MMI waveguide; and   the second input port is off-center from the center of the multiplexing MMI waveguide in a second direction opposite the first direction.   
     
     
         32 . The system for on-chip analyte detection of  claim 30 , wherein:
 the output port is off-center from the center of the multiplexing MIMI waveguide in the first direction and configured to output a self-image of light of the first wavelength and a mirror-image of light of light of the second wavelength.   
     
     
         33 . The system for on-chip analyte detection of  claim 30 , further comprising a detector configured to detect fluorescence bursts from an analyte excited by one or both of output light of the first wavelength and output light of the second wavelength. 
     
     
         34 . The system for on-chip analyte detection of  claim 30 , wherein:
 a height of the multiplexing MMI waveguide is less than or equal to: 0.1 μm, 0.5 μm, 1 μm, 2 μm, or 5 μm; and   a width of the multiplexing MMI waveguide is less than or equal to: 10 μm, 25 μm, 50 μm, 100 μm, or 250 μm.   
     
     
         35 . The system for on-chip analyte detection of  claim 31 , wherein an offset distance by which the first input port is off-center is greater than or equal to: 10%, 25%, or 45% of a width of the multiplexing MMI waveguide. 
     
     
         36 . The system for on-chip analyte detection of  claim 30 , wherein:
 a height of the analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm, or 10 μm; and   a width of the analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm, 10 μm, or 20 μm.   
     
     
         37 . The system for on-chip analyte detection of  claim 30 , wherein:
 a width of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm; and   a length of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm.   
     
     
         38 . A system for on-chip analyte detection, comprising:
 a substrate;   a first analyte channel, disposed on the substrate, configured to receive a first solution containing first analytes to be detected by the system; and   an adjustable liquid-core multi-mode interference (LC-MMI) waveguide, disposed on the substrate, that intersects the first analyte channel, the LC-MMI waveguide comprising:
 a first liquid-core portion comprising:
 a hollow channel configured to receive a first fluid; 
 side walls bounding the hollow channel; and 
 a first opening configured to allow the first fluid to flow into or out of the hollow channel; and 
 
 a first optical input port configured to receive input light of a first wavelength; 
   wherein the LC-MMI waveguide is configured to direct a first multi-spot pattern generated from the input light of the first wavelength onto the intersecting first analyte channel.   
     
     
         39 . The system for on-chip analyte detection of  claim 38 , wherein the first liquid-core portion is configured to allow the first fluid to flow out of the hollow channel and to replace the first fluid with a second fluid, the second fluid having a different index of refraction than the first fluid. 
     
     
         40 . The system for on-chip analyte detection of  claim 38 , further comprising a thermal control device, disposed on the substrate, configured to change a temperature of the first fluid, in order to thermally tune the LC-MMI waveguide, by greater than or equal to: 0.01 degree Celsius, 0.1 degree Celsius, 1 degree Celsius, 10 degrees Celsius, or 100 degrees Celsius. 
     
     
         41 . The system for on-chip analyte detection of  claim 38 , wherein:
 the system further comprises a second analyte channel, disposed on the substrate, configured to receive a second solution containing second analytes to be detected by the system; and   the LC-MMI waveguide further comprises a second liquid-core portion configured to direct a second multi-spot pattern generated from the input light of the first wavelength onto the intersecting second analyte channel, and configured to be adjustable independent of the first liquid-core portion.   
     
     
         42 . The system for on-chip analyte detection  claim 38 , further comprising a detector configured to detect fluorescence bursts from an analyte excited by first multi-spot pattern. 
     
     
         43 . The system for on-chip analyte detection of  claim 38 , wherein:
 a height of the hollow channel is less than or equal to: 0.1 μm, 0.5 μm, 1 μm, 2 μm, 5 μm, or 10 μm; and   a width of the hollow channel is less than or equal to: 10 μm, 50 μm, 100 μm, 250 μm, or 500 μm.   
     
     
         44 . The system for on-chip analyte detection of  claim 38 , wherein:
 a height of the first analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm or 10 μm; and   a width of the first analyte channel is less than or equal to: 1 μm, 2 μm, 5 μm, 10 μm, or 20 μm.   
     
     
         45 . The system for on-chip analyte detection of  claim 38 , wherein:
 a width of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm; and   a length of the substrate is less than or equal to: 2 mm, 5 mm, 1 cm, 2 cm, or 5 cm.   
     
     
         46 . The system for on-chip analyte detection of  claim 38 , further comprising a pressurization channel separated from the hollow channel by one or more of the side walls, wherein pressurizing the pressurization channel causes one or more of the side walls to deform to adjust a width of the first liquid-core portion. 
     
     
         47 . The system for on-chip analyte detection of  claim 38 , wherein the system is configured to pressurize the first fluid inside the liquid-core portion to cause one or more of the side walls to deform to adjust a width of the first liquid-core portion. 
     
     
         48 . The system for on-chip analyte detection of  claim 47 , wherein adjusting a width of the first liquid-core portion comprises adjusting the width by greater than or equal to: 0.1 μm, 0.5 μm, 1 μm, 5 μm, or 10 μm. 
     
     
         49 . The system for on-chip analyte detection of  claim 47 , wherein adjusting a width of the first liquid-core portion comprises increasing the width to be greater than or equal to: 125% of a static width of the portion, 150% of a static width of the portion, 200% of a static width of the portion, or 500% of a static width of the portion. 
     
     
         50 . The system for on-chip analyte detection of  claim 38 , wherein adjusting a width of the first liquid-core portion comprises decreasing the width to be less than or equal to: 1% of a static width of the portion, 10% of a static width of the portion, 25% of a static width of the portion, 50% of a static width of the portion, or 75% of a static width of the portion.