INTEGRATED PHOTONIC SYSTEMS AND METHODS FOR BIOSENSING
Disclosed herein are integrated photonics systems ( 3800 ) for biosensing including an interrogator photonic circuit ( 3802 ) and cartridge ( 3804 ) and methods using these systems. The cartridge ( 3804 ) comprises a sensor photonic integrated subcircuit. The cartridge ( 3804 ) is configured to receive a biological sample. The interrogator photonic circuit ( 3802 ) is optically coupled to the cartridge ( 3804 ) an comprises: (i) a light source ( 3806 ) configured to generate light; and (ii) one or more waveguides configured to carry the light, wherein the light is used to determine a characteristic of the biological sample in the cartridge ( 3804 ). A system can have an assembly of a plurality of modular photonic integrated subcircuits. Each subcircuit can be pre-fabricated and can be configured to transfer light to and receive light from another subcircuit based on the first functionality. An output port of a first subset of the subcircuits can be configured to be aligned with an input port of a second subset of the subcircuits. At least one subcircuit can be configured to be removed from the first integrated photonics assembly and connected to a second integrated photonics assembly having a second functionality. The first integrated photonics assembly can be different from the second integrated photonics assembly and the first functionality can be different from the second functionality.
1 . An integrated photonic system for biosensing, the system comprising:
a cartridge comprising a sensor photonic integrated subcircuit, the cartridge configured to receive a biological sample;
an interrogator photonic circuit optically coupled to the cartridge and comprising:
(i) a light source configured to generate light; and
(ii) one or more waveguides configured to carry the light,
wherein the light is used to determine a characteristic of the biological sample in the cartridge.
2 . The system of claim 1 , further comprising:
a stage configured to removably engage the cartridge and facilitate alignment of a light path of the interrogator photonic circuit and a light path of the cartridge.
3 . The system of claim 2 , wherein the stage comprises an ultrasound or a sound generator for at least one of: (i) preventing non-specific binding or (ii) mixing.
4 . The system of claim 1 , wherein the stage comprises at least one of: (a) a thermoelectric heater or (b) a thermoelectric cooler.
5 . The system of claim 1 , further comprising:
an isolation window disposed between the cartridge and the interrogator photonic circuit and configured to:
(a) physically isolate the interrogator photonic circuit from the biological sample, and
(b) enable the light to pass between the interrogator photonic circuit and the cartridge.
6 . The system of claim 1 , further comprising:
an alignment module configured to facilitate alignment between a light path of the cartridge and a light path of the interrogator photonic circuit.
7 . The system of claim 6 , wherein the alignment module actively facilitates alignment between the light path of the cartridge and the light path of the interrogator photonic circuit.
8 . The system of claim 6 , wherein the alignment module passively facilitates alignment between the light path of the cartridge and the light path of the interrogator photonic circuit.
9 . The system of claim 6 , wherein the alignment module enables an optical coupling efficiency greater than 10%.
10 . The system of claim 6 , further comprising:
an indicator coupled to the alignment module and configured to display a signal indicating whether the cartridge is aligned to the interrogator photonic circuit.
11 . The system of claim 6 , further comprising:
at least one lens configured to focus light between the interrogator photonic circuit and the cartridge.
12 . The system of claim 1 , wherein the interrogator photonic circuit comprises a control circuit configured to control the light.
13 . The system of claim 12 , wherein the control circuit comprises a detection circuit configured to detect the light.
14 . The system of claim 12 , wherein the light source is edge-coupled to the control circuit.
15 . The system of claim 12 , wherein the light source is coupled to the control circuit via an optical fiber.
16 . The system of claim 1 , wherein the cartridge comprises a microfluidic cell.
17 . The system of claim 16 , wherein the microfluidic cell comprises at least one of: (a) a magnetic microstirrer, (b) a plasmonic vortex mixer, or (c) a flow-inducing device.
18 . The system of claim 17 , wherein the microfluidic cell comprises the magnetic microstirrer, and wherein the system further comprises a stage configured to removably engage the cartridge and facilitate alignment of a light path of the interrogator photonic circuit and a light path of the cartridge, the stage comprising a transmitter configured to power the magnetic microstirrer.
19 . The system of claim 17 , wherein the flow-inducing device is an absorptive pad or a microfluidic capillary pump.
20 . The system of claim 1 , wherein the microfluidic cell comprises at least one of: (i) a protein, (ii) a reagent, or (iii) a rinsing fluid.
21 . The system of claim 1 , wherein the microfluidic cell comprises at least one microfluidic channel, a wall of the channel having an amplifier enzyme attached thereto.
22 . The system of claim 1 , wherein the stage is configured to receive a plurality of cartridges.
23 . The system of claim 1 , further comprising:
a splitter coupled to the light source; and
a frequency discriminator coupled to the splitter and configured to determine a change in a wavelength of the light source.
24 . The system of claim 23 , wherein the frequency discriminator comprises an unbalanced Mach-Zehnder interferometer (MZI), a Fabry-Perot cavity, a ring resonator, a gas cell, or a free-space etalon.
25 . The system of claim 23 , wherein the frequency discriminator comprises at least one of silicon, silica, or silicon nitride.
26 . The system of claim 1 , wherein the light source is tunable thermally, electrically, and/or mechanically.
27 . The system of claim 1 , further comprising:
a robotic device coupled to the interrogator photonic circuit and configured to position the cartridge to contact the biological sample.
28 . The system of claim 27 , wherein the robotic device is configured to discard the cartridge.
29 . The system of claim 27 , wherein the robotic device is configured to replace the cartridge automatically.
30 . A method for biosensing, the method comprising:
obtaining a biological sample in a cartridge, wherein the cartridge comprises a sensor photonic integrated subcircuit;
positioning the cartridge relative to an interrogator photonic circuit such that the cartridge is optically coupled with the interrogator photonic circuit, wherein the interrogator photonic circuit comprises (i) a light source configured to generate light, (ii) a waveguide configured to carry the light, and iii) a photodetector configured to detect said light after passing through said waveguides; and
determining, via the light, a characteristic of the biological sample in the cartridge.
31 . The method of claim 30 , further comprising:
determining, via an alignment module, whether the cartridge is optically coupled with the interrogator photonic circuit.
32 . The method of claim 31 , further comprising:
determining a coupling efficiency between the cartridge and the interrogator.
33 . The method of claim 30 , wherein said characteristic of the biological sample is determined based on a change in resonance, interference, or absorption caused by the biological sample.
34 . The method of claim 30 , wherein said waveguide is optically coupled to a probe.
35 . The method of claim 34 , wherein said probe binds specifically to a target biomolecule in said sample.
36 . The method of claim 35 , wherein said probe is an antibody, an antigen, or an aptamer.
37 . The method of claim 35 , wherein said target biomolecules is bound by a detection antibody.
38 . The method of claim 37 , wherein said detection antibody comprises an optically active component.
39 . The method of claim 34 , wherein a component of said biological sample initiates a cleavage of said probe.
40 . The method of claim 39 , wherein said probe comprises an optically active component.
41 . The method of claim 38 or claim 40 , wherein said optically active component is a plasmonic nanoparticle, a gold nanoparticle, a quantum dot, or a fluorophore.
42 . The method of claim 39 , wherein said probe comprises a silicon particle.
43 . The method of claim 39 , wherein said probe comprises a magnetic particle.
44 . The method of claim 43 , wherein said magnetic particle comprises iron-oxide.
44 . The method of claim 30 , wherein said waveguide comprises an optical ring resonator or an unbalanced Mach-Zehnder interferometer.
45 . The method of claim 39 , wherein said component of said biological sample activates a cleaving component.
46 . The method of claim 41 , wherein said component of said biological sample binds to a hairpin RNA encoding a cleaving component, wherein said binding facilitates translation of said RNA to generate said cleaving component.
47 . The method of claim 41 , wherein said cleaving component is a CRISPR enzyme.
48 . The method of claim 30 , wherein said cartridge further comprises an electromagnet.
49 . The method of claim 30 , wherein a target biomolecule of said sample is functionalized with a magnetic particle.
50 . A method for detecting a target biomolecule in a biological sample, comprising
providing a device comprising a sensor functionalized with a probe, wherein said probe can be cleaved by a cleavage enzyme;
adding said biological sample to said device, wherein the presence of said target biomolecule results in generation of or activation of said cleavage enzyme;
detecting cleavage of said probe by said cleavage enzyme, thereby detecting the presence of said target biomolecule in said biological sample.
51 . The method of claim 50 , wherein said cleavage enzyme is a CRISPR complex.
52 . The method of claim 51 , wherein said CRISPR complex is a Cas12 complex or a Cas13 complex.
53 . The method of claim 50 , wherein said target biomolecule is RNA or DNA.
54 . The method of claim 53 , wherein said target biomolecule binds to a hairpin RNA encoding said cleavage enzyme, wherein said binding facilitates translation of said hairpin RNA to generate said cleavage enzyme.
55 . The method of claim 50 , wherein said sensor is an electrical sensor, an optical sensor, or a combination thereof.
56 . The method of claim 50 , wherein said sensor comprises a ring resonator or a Mach-Zehnder interferometer.
57 . The method of claim 50 , wherein said probe comprises an optically active component.
58 . The method of claim 57 , wherein said optically active component is a plasmonic nanoparticle, a gold nanoparticle, a quantum dot, or a fluorophore.
59 . The method of claim 50 , wherein said probe comprises a silicon particle.
60 . The method of claim 50 , wherein said probe comprises a magnetic particle.
61 . The method of claim 60 , wherein said magnetic particle comprises iron-oxide.