Systems and Methods for Delivery of Light With Increased Omnidirectionality
20240222935 ยท 2024-07-04
Inventors
Cpc classification
H01S5/1042
ELECTRICITY
H01S2301/18
ELECTRICITY
International classification
Abstract
A laser microparticle for generating laser light with high omnidirectionality, including: an optical cavity including an active gain material capable of supporting one or more lasing cavity modes: and an optical scattering element which is incorporated into the optical cavity and configured to change a radiation pattern of the one or more lasing cavity modes to increase omnidirectionality of the radiation pattern, the size of the microparticle being less than 10 pm in each dimension.
Claims
1. A laser microparticle for generating laser light with high omnidirectionality, comprising: an optical cavity comprising an active gain material capable of supporting one or more lasing cavity modes; and an optical scattering element which is incorporated into the optical cavity and configured to change a radiation pattern of the one or more lasing cavity modes to increase an omnidirectionality of the radiation pattern.
2. The laser microparticle of claim 1, wherein the size of the microparticle is less than 10 ?m in each dimension.
3. The laser microparticle of claim 1, wherein the omnidirectionality of the radiation pattern is indicated by an omnidirectionality index, wherein the laser microparticle has an omnidirectionality index greater than 0.10.
4. The laser microparticle of claim 1, wherein the omnidirectionality of the radiation pattern is indicated by an omnidirectionality index, wherein the laser microparticle has an omnidirectionality index greater than 0.25.
5. The laser microparticle of claim 1, wherein the scattering element comprises a nanometer-scale roughness on the surface of the optical cavity.
6. The laser microparticle of claim 1, wherein the scattering element comprises at least one of a bump or a notch on the surface of the optical cavity.
7. The laser microparticle of claim 6, wherein the bump or the notch has a radius in a range of 50 nm to 400 nm.
8. The laser microparticle of claim 7, wherein the bump or the notch has a radius of 100 nm.
9. The laser microparticle of claim 1, wherein the scattering element comprises a nanoparticle.
10. The laser microparticle of claim 9, wherein the nanoparticle comprises high a refractive-index material.
11. The laser microparticle of claim 10, wherein the nanoparticle comprises at least one of silicon or a III-V semiconductor.
12. The laser microparticle of claim 9, wherein the nanoparticle has a diameter in a range of 30 nm to 200 nm.
13. The laser microparticle of claim 9, wherein the scattering element comprises a plurality of nanoparticles.
14. The laser microparticle of claim 13, wherein the plurality of nanoparticles comprises 5 to 50 nanoparticles per laser microparticle.
15. The laser microparticle of any one of claims 1-14, wherein the active gain material comprises a semiconductor.
16. The laser microparticle of any one of claims 1-14, wherein the optical cavity comprises a microdisk.
17. The laser microparticle of claim 16, wherein the scattering element comprises a feature layered axially with respect to the microdisk, wherein the feature has a different radius than the microdisk.
18. A microparticle for generating laser light comprising: an optical cavity comprising a microdisk including an active gain material capable of supporting one or more lasing cavity modes; and an optical scattering element associated with the optical cavity and configured to change a radiation pattern of the one or more lasing cavity modes to increase omnidirectionality of light introduced into the optical scattering element.
19. The microparticle of claim 18, wherein the microdisk has a diameter of less than 10 ?m.
20. The microparticle of claim 18, wherein the omnidirectionality of the radiation pattern is indicated by an omnidirectionality index, wherein the laser microparticle has an omnidirectionality index greater than 0.10.
21. The microparticle of claim 18, wherein the omnidirectionality of the radiation pattern is indicated by an omnidirectionality index, wherein the laser microparticle has an omnidirectionality index greater than 0.25.
22. The microparticle of claim 18, wherein the optical scattering element comprises a modification of a surface of the microdisk.
23. The microparticle of claim 22, wherein the modification of the surface comprises a modification of an edge of the microdisk.
24. The microparticle of claim 23, wherein the modification of the edge of the microdisk comprises a nanometer-scale roughness in a surface of the optical cavity.
25. The microparticle of claim 23, wherein the modification of the edge of the microdisk comprises at least one of a bump or a notch on the edge of the microdisk.
26. The microparticle of claim 25, wherein the bump or the notch has a radius in a range of 50 nm to 400 nm.
27. The microparticle of claim 26, wherein the bump or the notch has a radius of 100 nm.
28. The microparticle of claim 22, wherein the modification of the surface of the microdisk comprises a nanoparticle coupled to the microdisk.
29. The microparticle of claim 28, wherein the nanoparticle comprises a high refractive-index material.
30. The microparticle of claim 29, wherein the high refractive-index material comprises at least one of silicon or a III-V semiconductor.
31. The microparticle of claim 28, wherein the nanoparticle has a diameter in a range of 100-200 nm.
32. The microparticle of claim 28, wherein the microdisk includes between 10 and 50 nanoparticles.
33. The microparticle of claim 18, wherein the modification of the surface of the microdisk comprises a feature layered axially with respect to the microdisk, wherein the feature has a different radius than the microdisk.
34. The microparticle of any one of claims 18-33, wherein the active gain material comprises a semiconductor.
35. A laser generating microparticle comprising: an optical cavity; an active gain material arranged in the optical cavity and configured to operate according to one or more lasing cavity modes; and an optical scattering element associated with the optical cavity and configured to change a radiation pattern of the one or more lasing cavity modes to direct light in a plurality of different directions when the light is introduced into the optical scattering element.
36. The microparticle of claim 35, wherein the microparticle has a diameter of less than 10 ?m.
37. The microparticle of claim 35, wherein the omnidirectionality of the radiation pattern is indicated by an omnidirectionality index, wherein the laser microparticle has an omnidirectionality index greater than 0.10.
38. The microparticle of claim 35, wherein the omnidirectionality of the radiation pattern is indicated by an omnidirectionality index, wherein the laser microparticle has an omnidirectionality index greater than 0.25.
39. The microparticle of claim 35, wherein the scattering element comprises a nanometer-scale roughness formed on a surface of the microparticle surrounding the optical cavity.
40. The microparticle of claim 35, wherein the scattering element comprises at least one bump or notch on a surface of the microparticle surrounding the optical cavity.
41. The microparticle of claim 40, wherein the bump or notch has a radius in a range of 50 nm to 400 nm.
42. The microparticle of claim 41, wherein the bump or notch has a radius of 100 nm.
43. The microparticle of claim 35, wherein the scattering element comprises a nanoparticle.
44. The microparticle of claim 43, wherein the nanoparticle includes at least one of silicon or a III-V semiconductor.
45. The microparticle of claim 43, wherein the nanoparticle has a diameter in a range of 100 nm to 200 nm.
46. The microparticle of claim 43, wherein the scattering element includes between 10 and 50 nanoparticles.
47. The microparticle of any one of claims 35-46, wherein the optical cavity comprises a microdisk.
48. The microparticle of any one of claims 35-46, wherein the active gain material comprises a semiconductor.
49. A method of generating laser light with high omnidirectionality comprising delivering one or more microparticles of claim 1 to a sample.
50. The method of claim 49, wherein the sample is a biological sample.
51. The method of claim 50, further comprising using the one or more microparticles as an optical probe of the biological sample.
52. A microdisk laser particle including light scattering elements configured to increase omnidirectionality by directing emission intensity of whispering gallery modes in the direction along a plane of the microdisk to a plane normal to the plane of the microdisk.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Various objects, features, and advantages of the disclosed subject matter can be more fully appreciated with reference to the following detailed description of the disclosed subject matter when considered in connection with the following drawings, in which like reference numerals identify like elements.
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DETAILED DESCRIPTION
[0041] An intrinsic feature of LPs is that their output emission occurs in specific directions determined by the lasing cavity mode. Microdisk LPs supporting whispering gallery modes (WGMs) emit predominantly in the plane of the cavity resonance. The directionality of laser emission, however, hinders the reliable optical reading of LPs when their orientations with respect to optical instruments change. This is a general problem in almost all applications of LPs as this new type of lasers are intended to operate with arbitrary, often freely-moving, orientations. Cell tracking represents this situation. The orientations of LPs in a cell is arbitrary and tends to vary over time as the cell moves. During tracking this can cause random intensity fluctuations and frequent loss of the measured laser signal, making it difficult to detect and identify the LPs reliably over time. We have encountered this problem in our previous study of spheroids in vitro. The light scattering in biological tissues does not mitigate this problem because the high-resolution spectral readout of LP emission requires confocal detection of essentially non-scattered, or minimally-scattered, light. Furthermore, the detection of LPs in instruments with dynamic environments such as microfluidic channels would severely suffer from the angular dependence of emission. Therefore, addressing the directionality of laser emission would have a high impact on the broad utilities of LPs.
[0042] Previous work on microlasers for on-chip applications mainly focus on directing the in-plane emission of WGM microlasers to a specific direction by introducing boundary deformations, diffraction gratings, or scatterers. Nevertheless, omnidirectional laser emission into 4? steradians has neither been attempted nor demonstrated. Liquid-crystal microspheres have the potential of omnidirectional lasing but the large resonator size (tens-of-micrometers) required to form a radial grating is unsuitable for intracellular applications.
[0043] Here, we demonstrate omnidirectional emission from microdisk LPs by incorporating light scattering into the cavity. Among the various approaches we have explored, two designs of omnidirectional LPs (OLPs) are described here: one introduces boundary defects on the cavity design, and the other uses nanoparticles attached around the resonators. The laser power collected from our OLPs varies by less than 10 dB as a function of their orientation, while this same variation exceeds 24 dB for conventional microdisk LPs (CLPs). We find that despite the strong scattering and large aspect ratio of both OLP designs, single-mode lasing is realized with low lasing threshold and narrow linewidth nearly independently of their orientation. We have applied one of the designs to produce OLPs in large quantities for a proof-of-concept demonstration of reliable single-cell tagging and blinking-free cell tracking. Traces of OLPs based on their output spectra in live cells show a high signal-to-noise ratio (SNR) in every single frame for two hours in practical settings, while with CLPs the signal is below the noise level in many frames.
[0044] Accordingly, various embodiments provide a microparticle for generating laser light. The microparticle may include an optical cavity which may include a microdisk having an active gain material capable of supporting one or more lasing cavity modes, where the active gain material may include a semiconductor.
[0045] The microparticle may also include an optical scattering element associated with the optical cavity and configured to change a radiation pattern of the one or more lasing cavity modes to increase omnidirectionality of light introduced into the optical scattering element. In certain embodiments the microdisk may have a diameter of less than 10 ?m. In some embodiments, the omnidirectionality of the radiation pattern is indicated by an omnidirectionality index, which in particular embodiments may be greater than 0.10 or greater than 0.25.
[0046] In various embodiments, the optical scattering element includes a modification of a surface of the microdisk. In some embodiments, the modification of the surface may include a modification of an edge of the microdisk. In particular embodiments, the modification of the edge of the microdisk may include a nanometer-scale roughness in a surface of the optical cavity. In other embodiments, the modification of the edge of the microdisk may include at least one of a bump or a notch on the edge of the microdisk, where the bump or the notch may have a radius in a range of 50 nm to 400 nm, and in particular may have a radius of 100 nm.
[0047] In certain embodiments, the modification of the surface of the microdisk may include a nanoparticle coupled to the microdisk, where the nanoparticle may include a high refractive-index material which may include at least one of silicon or a III-V semiconductor. In various embodiments, the nanoparticle may have a diameter in a range of 100-200 nm. In some embodiments, the microdisk may include between 10 and 50 nanoparticles.
[0048] In one embodiment, the optical scattering element may include a feature layered axially with respect to the microdisk, wherein the feature has a different radius than the microdisk.
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[0051] When the microdisk is oriented with an angle 210 with respect to the light collection direction 214, the measured output intensity 220 has a strong angle dependence or directionality. For example, the output intensity curves 230, 234, 238 of three different microdisks 250, 254, 258, measured as a function of pump pulse energy are shown in
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[0053] We introduce a scattering coefficient s, where I.sub.un-sc(?)=(1?s)I.sub.0(?). The specific form of I.sub.sc(?) depends on the specific shape, size, and distribution of the scatterers, but when the characteristic size of the roughness in the surface is much less than the optical wavelength, e.g. <20 nm, I.sub.sc(?) can be expressed as s*I.sub.Rayleigh(?), where I.sub.Rayleigh(?) describes a dipolar radiation pattern with lobes toward the vertical (disk-plane normal) directions.
[0054] For s<<1, the omnidirectional index is approximately equal to s/(1?s). The index is maximized 1 when s=0.5. For practical applications, an omnidirectionality index greater than 0.1 is desirable. This can be achieved with a scattering coefficient s greater than 0.1. This condition may be achieved by deliberately introducing sufficiently large roughness on the side surface of microdisk lasers.
[0055] Another approach to increase the scattering coefficient relative to a pristine microdisk 100 is to introduce one or more defined defects, such as bump 344 or notch 340 elements (
[0056] Where the first term describes un-scattered light 350 and the second term describes vertically scattered light 354.
[0057] Another effective approach is to attach scattering elements to microdisks 360 (
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[0066] For example, a-Si could be deposited by PECVD on the surface of the cavity material 1110. Following definition of disk geometry, the size of the a-Si could be finely tuned by, for example, a number of XeF.sub.2 etching cycles, which is a known technique used in precision silicon MEMS fabrication. To prevent thinning of the a-Si, it would be possible to cap the a-Si with a silica layer, which could later be removed selectively by HF etching. Alternatively, the thin, residual pedestals could be made of a material grown lattice matched to the original substrate. For example, a composition of In.sub.xGa.sub.1-xAs.sub.1-yP.sub.y with x and y close to 1 would resemble InP and so would etch faster in HCl than an In.sub.xGa.sub.1-xAs.sub.1-yP.sub.y disk with x<x, y<y, enabling residual pedestals 1120 and 1130 of the material to remain attached to the detached microparticle.
[0067] In summary, disclosed herein are several working embodiments of microdisk lasers having improved omnidirectionality in output emission. A single microdisk has been considered in the embodiments, but the same principle based on scattering can be applied to multiple laser particles, each of which consists of multiple (typically 2 to 9) microdisks for generating multiple laser emissions. While the exemplary embodiments are demonstrated with semiconductor microdisk lasers, the same approach based on incorporating scattering elements at and near the surface of optical cavities can be extended for other types of LPs, such as microsphere lasers, organic micro-lasers, semiconductor nanowires, and submicron laser particles, where surface roughness, bumps, notches, and nanoparticles can be used to increase omnidirectionality. Overall, the scattering-based strategy to improve omnidirectionality can be applied to various laser particles with a size ranging from 0.5 ?m to 10 ?m. Furthermore, this approach is applicable to optical microcavity particles to alter the input and output coupling of cavity resonance modes.
Examples
[0068] Following are non-limiting examples of procedures that may be performed using one or more of the disclosed apparatus, methods, or systems:
In-Plane Emission of Microdisk LPs
[0069] Semiconductor microdisk lasers using InGaAsP active gain material were produced using established procedures. The microdisks were released from the substrate by wet chemical etching and loaded into cells. The orientation of LPs in tagged cells is arbitrary (
[0070] Consider a typical semiconductor microdisk laser with a diameter of 2 ?m and thickness 200 nm. Finite-element-method (FEM) simulations identify the transverse-electric (TE, meaning E.sub.z=0) WGM at a representative wavelength of 1270 nm (
[0071] The output emission is collected with a finite numerical aperture (NA). For a microdisk LP tilted with respect to the viewing axis by an angle ?, the power collected is given by
[0072] where the integration is performed over the solid angle Q defined by a cone with half angle ? sin(NA/n) centered on ? (
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[0074] The criterion for omnidirectionality may be defined as R >0.01 or ?20 dB, since this could result in an adequate SNR when a spectrometer with a typical dynamic range of 30 dB is used. We consider R>0.1 highly omnidirectional. It should be noted that R is a function of the NA of light collection (See below,
[0075] To characterize the angle dependence experimentally, we suspended microdisk LPs in a curable gelatin hydrogel (Matrigel, n=1.334) with fixed, random orientations and examined them under a laser-scanning confocal microscope combined with a pump laser (1064 nm wavelength, 3 ns pulse width, 2 MHz repetition, and 2.9 ?m focal beam size) and a high-resolution spectrometer (Materials and methods). Upon optical pumping above their lasing threshold, the microdisk LPs exhibited single-mode emission with a sub-nm linewidth (
Omnidirectional-Emitting Laser Particles (OLP)
[0076] Although the output emission of a CLP is directional because of the innate geometry of its cavity structure, it is possible to transform the emission pattern by introducing perturbations. For example, surface roughness, boundary deformations or nanoscale scatterers could redirect part of the lasing light to directions out of the disk plane by elastic scattering (
[0077] where s represents the fraction of light scattered, c.sub.0?0.75 and c.sub.1=0.21 (see below). Therefore, the min-max ratio becomes R=0.56 s/(1?0.72 s). The criteria of R>0.01 and R>0.1 are satisfied when s>0.018 and s>0.16, respectively.
[0078] So far, we have considered the light collected from a microdisk. As the LP changes its orientation with respect to the excitation and collection optics (
LPs with Surface Roughness
[0079] Nanometer-scale imperfections behave as Rayleigh scatterers and couple the resonant optical modes into far-field radiation. Conventional wisdom states that one ought to strive to reduce such imperfections during fabrication to maximize the quality factor of the laser cavity and thereby reduce the lasing threshold. We hypothesized that the sidewall roughness arising from reactive ion etching (RIE) can be intentionally introduced to reduce the emission directionality of microdisk LPs without significantly affecting lasing threshold.
[0080] To investigate this approach, as a control group we measured a batch of CLPs with smooth sidewalls (
[0081] The fitting parameter s=0.007 with the scattering model (Eq. (4), green curve) reveals that the small imperfections on the LPs' surface only scatter 0.7% of the output emission on average and result in a small R?0.004 or ?24 dB for this CLP ensemble. This value of R is likely to be overestimated because ?'s less than 10.sup.?3 are not reliably measured due to the finite dynamic range of the spectrometer. Lasing thresholds were found to be 13?5 pJ, showing very low dependence on disk orientation (
[0082] To increase the surface roughness, we fabricated LPs in the same way as the CLPs but using a different RIE chemistry that produces rougher sidewalls. This resulted in a batch of LPs with an azimuthal variation of ?50 nm in the disk radius (
LPs with Defined Boundary Defects
[0083] To further improve upon these results, we artificially introduced sub-wavelength semicylindrical defects with a negative (notch) or positive (bump) curvature. Simulation results illustrate that P.sub.tot(0?), which is almost entirely due to out-of-plane scattering from the boundary defect, increases with increasing defect size (
[0084] Experimentally we induced a notch or a bump with a diameter of 200 nm in microdisks using electron-beam lithography and roughness-inducing RIE processes. The resulting nanostructure is shown in
[0085] Notched LPs with rough sidewalls (
LPs Coated with a Scattering Layer (scLPs)
[0086] An alternative approach to achieving omnidirectional emission is to incorporate extra-cavity inhomogeneities. This could be realized by coating the microdisks with nanoparticles with large refractive index but low absorption loss. We chose silicon nanoparticles (SiNPs) due to their high refractive index of 3.48 and nearly zero imaginary part at near-infrared wavelengths. In a 3D FEM model, SiNPs were randomly placed on top of a microdisk and a thin silica coating layer was applied. The simulation result confirmed a strong light scattering effect of the monolayer of SiNPs (
[0087] To realize this design, we devised a novel top-down fabrication method (
[0088] In this experiment, an InGaAsP wafer with a gain bandwidth of ?1400-1500 nm was used. The output emission of an scLP in hydrogel typically features a single peak with a FWHM of 0.25 nm (
Continuous Cell Tracking Using OLPs
[0089] To demonstrate the detection reliability of omnidirectionally-emitting LPs for cellular tracking, ?10.sup.5 OLPs (scLPs) and CLPs (cLPs) were fabricated and separately transferred into cell media for HeLa cell coculture. Within 12 hours of incubation in vitro, both CLPs and OLPs were efficiently internalized by cells through the non-specific process of macropinocytosis. The orientation of loaded LPs was observed to vary continuously within the cells, resulting in random disk orientations at any given moment.
[0090] Using a custom-modified confocal microscope, bright-field images and lasing emission of LPs in cells were obtained as ground-truth data for tracking CLPs and OLPs in live Hela cells (
[0091] Next, we acquired time-lapse maps of several LPs of each type over a period of 2 hours. Because of the random-walk movement of LPs inside the cytoplasm, we scanned the focal plane in the z-direction to obtain Z-stack lasing maps and bright-field images every 3 min for 2 hours. Since LPs have single-mode emission with sub-nanometer linewidth (
[0092] Thus various embodiments of highly omnidirectional LPs have been demonstrated which have a min-max ratio R??5.7 dB, low threshold, narrow linewidth, and single-mode lasing, which enable reliable cell tagging and continuous cell tracking. We expect OLPs to enhance tracking reliability in applications including deep tissue imaging, where intrinsic tissue scattering does not overcome the low signal collection efficiency from flat disks (See below). The scattering elements introduced at the boundary and flat surface were effective, directing up to 20-32% (s=0.20-0.32) of the collected laser emission to all directions.
[0093] To enable long-term operation in aqueous biological environments, the semiconductor LPs may need an additional protective layer. The simulated results in
[0094] The high-brightness omnidirectional emission significantly improves the SNR of LPs, resulting in reliable spectral identification and spatial tracking without increasing exposure times. OLPs allow for continuous and high-speed tracking of single cells, which, combined with the massive spectral multiplexing capability of LPs, enables the study of cellular heterogeneity at the single-cell level in large-scale 3D biological specimens. Besides cell tracking, omnidirectionality will facilitate other applications of LPs, such as cellular and biochemical sensing and single-cell analysis in microfluidics, by ensuring high SNR.
Fabrication and Transfer of LPs
[0095] Microdisk resonators were fabricated starting from epitaxially-grown III-V semiconductor wafers consisting of a 300-nm-thick buffer layer of undoped InP, a 200-nm-thick active gain material layer of InGaAsP, and a 100-nm-thick capping layer of undoped InP over an InP substrate.
[0096] Defect LPs by e-beam lithography: Microdisk lasers with nanoscale protrusions or indentations were fabricated on the semiconductor wafers. The patterns were defined by 100 keV electron-beam lithography (JBX6300FS, JEOL) on a negative-tone resist (SU-8, 50% dilution), and transferred to the semiconductor by reactive-ion etching (Oxford Plasmalab 100 ICP) using a mixture of chlorine and argon. The remaining resist was removed by oxygen and fluoroform plasma treatment, and ultrasonic agitation in an N-methyl-2-pyrrolidone-based organic solvent at elevated temperatures (Microposit Remover 1165, Dow Chemicals). Corresponding control samples with circular shapes were fabricated by the same method. For the on-pillar disks, the supporting pillars were undercut by wet chemical etching in diluted HCl. During this last step, the capping layer is also removed. Samples with intentional surface roughness were fabricated following a similar process flow, but using hydrogen bromide chemistry during RIE.
[0097] Control LPs (cLPs) and scLPs by optical lithography: First, the InP capping layer was removed by etching in 3:1 HCl:H.sub.2O for 10 s. Cleaning of the surface was then performed using acetone, isopropyl alcohol (IPA) and water followed by O.sub.2 plasma (30 s, 100 W, 40 sccm O.sub.2) (SCE 106, Anatec Ltd). Next, 15 nm of SiO.sub.2 was deposited by plasma-enhanced chemical vapor deposition (PECVD) (Surface Technology Systems). Silicon nanoparticles (30-50 nm, US Research Nanomaterials, Inc) in IPA were filtered using a centrifuge filter (pore size: 450 nm), and particle aggregations were broken up by a probe sonicator (Fisher Scientific). Immediately before spinning the silicon nanoparticles, the individual chips were cleaned using O.sub.2 plasma (60 s, PE-25, Plasma Etch Inc.). The newly deposited silica layer was wetted with IPA and spread uniformly across the chip at a spin speed of 2000 rpm for 45 s (Laurell Technologies Corporation). 20 ?l of Si nanoparticles suspended in IPA was dynamically dispensed at 600 rpm before increasing the spin speed to 3000 rpm where it was held for a time of 120 s, during which the IPA fully dried. During this spin-coating step, silicon nanoparticles aggregates approximately a hundred nanometers in scale form on the wafer surface (
[0098] Next, a second 250-nm-thick layer of SiO2 was deposited by PECVD to fully incorporate the nanoparticles into the silica shell. The surface was then cleaned using the O.sub.2 plasma (120 s, Matrix 105). To enhance photoresist adhesion to the SiO2 film, an adhesion promoter (Omnicoat MicroChem) was used before spin-coating (Headway Research, Inc.) the surface with a 3 ?m-thickness layer of photoresist (SU8-2002 MicroChem). Soft baking procedures followed the manufacturer's guidelines. The 2.5 ?m-diameter circles of SU8 photoresist (Density: ?3.2 million/cm.sup.2) were then defined using a projection exposure tool (MLA150, Heidelberg Instruments) at a dose of 1500 mJ/cm.sup.2 at a wavelength of 375 nm. A two-step post-exposure bake was used, consisting of 60 s at 65? C. followed by 180 s at 95? C. on a contact hotplate. The resist was developed for 60 s in SU8 Developer (MicroChem). To smoothen the sidewalls of the resist and harden it for dry etching, a further bake at 190? C. for 10 minutes was performed on a contact hotplate. The residual photoresist was removed using a 90 s descum at 100 W, 40 sccm O.sub.2 (SCE 106, Anatec Ltd). Next, inductively coupled reactive ion etching (ICP-RIE) using a fluorine-based chemistry was performed (Surface Technology Systems) to define columns consisting of Si nanoparticles embedded in the silica film. Any remaining SU8 resist was subsequently removed using O.sub.2 plasma ashing (Matrix 105) for 10 minutes at 220? C. The Si/SiO2 columns were used as a hard mask for an III-V ICP-RIE process which etched depth of approximately 1 ?m using a chlorine-based chemistry (PlasmaPro 100 Cobra 300, Oxford Instruments).
[0099] The corresponding control samples with a silica-capping layer were prepared with the same method without spinning the silicon nanoparticles. For completely detaching the microdisks, the substrates were wet-etched face down in 3:1 HCl:H.sub.2O solution inside a 1 ?m pore centrifuge filter for 30 s and filtered thoroughly by at least 3 repeated cycles of centrifugation and resuspension (via ultrasonication) using ultrapure water.
Optical Characterization
[0100] For optical characterizations and imaging of microdisks, a laser-scanning LASE microscope modified from a commercial confocal microscope (Olympus FV3000) was used. A pump laser (Spectra Physics VGEN-ISP-POD, 1060-1070 nm, pulse duration 3 ns, repetition rate 2 MHZ) with the output power controlled by an acoustic optical modulator and measured by an external Photodetector, was coupled to a side port of the laser-scanning unit of the microscope. The day-to-day variation in the measurement of absolute pump power is up to 30%. The emission from microdisks was collected from the same port and relayed by a dichroic mirror to a NIR spectrometer using an InGaAs linescan camera (Sensor Unlimited 2048L). 100 lines/mm grating (0.6-nm resolution over 1150-1600 nm, exposure time: 0.1 ms) was used for threshold characterization, and a 500 lines/mm grating was used for high-resolution linewidth characterization (0.2-nm resolution, 150-nm span, exposure time: 0.1 ms). In both cases, a NIR-optimized, 20?, 0.45-NA objective (Olympus IMS LCPLN20XIR) were used. The high-resolution lasing mapping images were acquired with a 100?, 0.85-NA objective (Olympus IMS LCPLN100XIR) and the NIR spectrometer with the 100 lines/mm grating (0.6-nm resolution over 1150-1600 nm, exposure time: 0.1 ms).
Numerical Simulation of Far-Field Pattern
[0101] The modeling of passive microdisk resonance was conducted via a series of three-dimensional finite-element simulations (COMSOL Multiphysics 5.3a). We set the refractive indices of the microdisk and hydrogel to be 3.445 and 1.334 respectively. The optical absorption of bulk semiconductor material and laser gain are not considered here. The shape and size of the disk agree with that of the semiconductor laser particles we used in our experiment (obtained by SEM). The thickness of the disk is 200 nm, the diameter of defect LPs and corresponding control LP made by e-beam lithography is 2 ?m, and the diameter of scLPs and corresponding control LPs are 2.5 ?m. The simulation region was set with perfectly matched layer boundary conditions in all directions. The distance to the perfectly matched layer boundaries as well as the meshing size were chosen after a series of convergence tests. We used the eigen-frequency study (Physics: Radio Frequency, frequency domain) and the far-field domain plug-in to calculate the far-field pattern of WGM mode. The randomly distributed nanoparticles for scLPs were generated by an application-builder module. The calculated intensity pattern (|E.sub.far(?,?)|.sup.2) was exported, and a MATLAB script was used to calculate output pattern through the integration over the acceptance solid angle ?=2?[1?cos(sin.sup.?1(NA/n))]=0.37 steradian (Eq. (3)). Finally, the output pattern P.sub.tot(?) was normalized by the total output energy.
Cell-Culture Experiments
[0102] HeLa human cervical cancer cells (ATCC) were cultured and maintained with Dulbecco's modified Eagle medium (DMEM) supplemented with 10% (v/v) fetal bovine serum (FBS) and 1% (v/v) penicillin-streptomycin. Cells were seeded in 8 well-chambered glass dishes (Cellvis) at a density of 15,000 cells/cm.sup.2. After 24 hours, 60,000 scLPs were added to one of the culture wells, and 60,000 control LPs were added to a control well, along with the requisite quantity of 10?PBS to ensure isotonicity of the final solutions. After 1 hour, the cell media was aspirated and replaced with a fresh volume. The cells were then incubated (Thermo Scientific Heracell 240i) with the LPs at 37? C. and 5% CO.sub.2 for 8 hours to give sufficient time for LP uptake. During imaging, cells were incubated using a microscope stage top incubator (Tokai Hit).
[0103] Cell tracking experiments were performed by acquiring time-lapse data every 3 minutes over a total period of 2 hours. During the measurement, cells were placed in a temperature-controlled cell-culture incubator. Six regions were defined: three from the scLPs well and three from the control well. Each region, consisting of 320?320?7 voxels corresponding to a volume of 212?212?21 ?m.sup.3, was scanned with an NIR pump laser (Spectra Physics VGEN-ISP-POD, pulse duration 3 ns, repetition rate 2 MHz, pulse energy 160 pJ), using a pixel dwell time of 20 ?s. Brightfield images were recorded simultaneously with the acquisition of spectral LP emission. For each microdisk, the integrated intensity of the lasing peak was calculated for all spectral frames associated with the disk. Orientations were obtained by analyzing the brightfield images using ImageJ and the orientation angle was then associated with the maximum integrated intensity of each disk's lasing peak.
[0104] Fluorescent imaging was obtained by washing the cells three times with PBS, fixed with 4% paraformaldehyde/PBS (Fisher Scientific), permeabilized with 0.1 Triton X-100/PBS (Fisher Scientific) and incubated with AlexaFluor 594-Phalloidin (Thermo Fisher) for actin staining and NucBlue Fixed Cell Stain (Thermo Fisher Scientific) for nuclear staining, following manufacturer guidelines.
Far-Field Modeling of WGM Resonance
[0105] A scalar diffraction theory of light emanating from a microdisk of radius R into the far-field is given in the spherical coordinates (r, ?, ?), as:
[0106] where k=n?/c is the wave number, w is the angular frequency, n is the refractive index of external environment of the microdisk, F is the Fourier transform of the near-field distribution f(z) on the cylindrical surface ?=R in cylindrical coordinate (?, ?, z), and H.sup.(2).sub.m is the Hankel function of the second kind.
[0107] Considering a typical semiconductor microdisk laser (refractive index 3.445, radius R=1 ?m, and thickness of 200 nm), the m=10th-order TE WGM at the resonant wavelength of 1270 nm is obtained by a 3D FEM simulation (
[0108] Experimentally, the output emission is collected by a lens with a finite numerical aperture (NA). The power collected from a microdisk that is tilted with respect to the viewing axis by an angle ? is given by
[0109] where the integration is performed over the solid angle defined by a cone with half angle ? sin(NA/n) centered on a.
[0110] The ratio R of the minimum and maximum intensities as a function of NA
[0111] To quantify the angle dependence of P.sub.signal, we calculate the ratio R of the minimum and maximum collected powers from the result of Eq. 6. Note that R is a strong function of the NA of light collection.
[0112] In this work, we consider a LP with R>0.01 as being omnidirectional, and R>0.1 as highly omnidirectional. These conditions could be achieved with a CLP when NA>1.1 and NA>1.2, respectively. Using such high NA, however, may not be allowed in certain instruments, nor be a desirable solution because its diffraction-limited volume at the focus would become much smaller than the size of an LP, reducing the collection efficiency and causing intensity variations depending on the focal position. For LPs with a size of D and wavelength of ?, the maximum NA without significantly losing collection efficiency is ??/D. For D=2 ?m and ?=1270 nm, the collection NA should be less than 0.64. As heuristic approximates, for NA<0.7 we find P.sub.signal(a, NA)/|sin ?|.sup.q, where q?18-18*NA and R<?60 dB.
Scattering Model
[0113] The nanoscale surface roughness, boundary deformations or external particles could scatter part of emitted and intracavity light to directions out of the disk plane by elastic scattering. The Rayleigh-scattered intensity P.sub.sc(?) should have the maximum when ?=0? and the minimum at 90? because the electric field of the TE mode is polarized primarily in the plane of the disk (
[0114] While a conventional LP predominantly emits in the radial direction, scattering predominantly radiates orthogonally to this plane about the ?=0? axis, which we define as the +z axis. Notice that we can rewrite the angle dependence of the scattering radiation in terms of the spherical unit vector {right arrow over (r)}=sin ? cos ?{right arrow over (x)}+sin ? sin ?{right arrow over (y)}+cos ?{right arrow over (z)}.
[0115] To account for rotation of the microdisk LP, we use a standard rotation matrix to rotate {right arrow over (r)} about the x-axis by some angle ? to yield a new vector
[0116] Therefore, we expect the number of scattered photons collected by our optical setup for a disk tilted from horizontal by an angle ? to be given by
[0117] where ?.sub.0 defines the collection angle of the objective. Evaluating this integral gives
[0118] where going from the first to second line we have used the paraxial approximation cos x=1?x.sup.2/2. This suggests that a sinusoidally quadratic emission pattern retains the general form of its angle dependence when its emission is collected by a paraxial optical system, i.e.
[0119] Combining the in-plane emission from the microdisk and the out-of-plane scattering from the perturbations, the total pattern of OLP can be expressed as
[0120] where P.sub.0(?) is the intrinsic emission of the lasing mode in the perturbed LP, P.sub.sc(?) denotes the intensity pattern arising from scattering objects, and s represents the fraction of light scattered. If the perturbation to the lasing mode is small, P.sub.0(?) would be close to P.sub.signal. The Rayleigh-scattered intensity P.sub.sc(?) should have the maximum at ?=0? and the minimum at 90?. The original and scattered profiles are thus complementary and could constitute omnidirectional emission for sufficiently large s. With appropriate normalization factors, Eq. (13) may be written as, for NA<0.7:
[0121] where c.sub.0=?.sup.4? sin.sup.18? d?/?.sup.4? sin.sup.q? d??0.75 for NA=0.45 (q=10) and c.sub.1=?.sup.4? sin.sup.18? d?/?.sup.4? (1+cos.sup.2?) d??0.21, c.sub.1/c.sub.0=?4? sin.sup.q? d?/?.sup.4? (1+cos.sup.2?) d??0.28. Putting these values into Eq. (14), we find the min-max ratio to be:
[0122] The criteria of R >0.01 and R >0.1 are satisfied when s >0.018 and s >0.16, respectively.
scLPs Obtained by Chemical Functionalization
[0123] We have developed silica coating on LPs by a modified Stober method. Therefore, we can also adsorb scatterers onto LP templates by a chemical bonding method, which has widely been used to conjugate various nanoparticles and biomolecules onto silica surface with chemical modifications. Firstly, a numerical simulation was performed to illustrate the feasibility of this approach. As an example, 47 nanospheres with a diameter of 200 nm are randomly distributed on the surface of a LP with a 50-nm-thick silica gap, as shown in the device models (
[0124] In the experiment, we used commercially-available TiO.sub.2 nanospheres functionalized with carboxyl groups as scatterers on silica coated LPs. The scLP production process is described in
Methods of scLPs Obtained by Chemical Functionalization.
[0125] Silica coating: Silica coating of the microdisks was performed by a modified Stober process. A typical silica coating with a thickness of 50 nm is as follows: Microdisks (about 105 LPs/ml) were suspended in 670 ?l of ethanol:H.sub.2O solution (80 v/v % ethanol). Next, 60 ?l of 40 mM tetraethyl orthosilicate (TEOS) in ethanol, and 45 ?l of ammonium hydroxide solution (28 v/v % NH.sub.4OH) were added, and the microdisk solution was shaken vigorously at 1,400 rpm. for 1 h at room temperature. To harden the silica shell and improve chemical stability, the temperature was increased to 70? C. and the solution was mixed for an additional 2-12 hours. Then, the microdisks were filtered out by a transwell centrifuge filter with a pore size of 1 ?m. To remove the small silica nanoparticles, the microdisks in the transwell centrifuge filter were sonicated for 5-10 mins in DI water and thoroughly centrifuge-filtered 3-4 times. Amino functionalization: The silica-coated microdisk was suspended in 950 ?l of ethanol solution. Then, 40 ?l of NH.sub.4OH and 10 ?l of (3-aminopropyl)-triethoxysilane (APTES) were added, and the microdisk solution was shaken vigorously at 1,400 r.p.m. overnight at room temperature. The suspension of microdisks was then transferred to a 1 ?m-pore centrifuge filter, and filtered thoroughly by at least three repeated cycles of centrifugation and resuspension (via ultrasonication) using ethanol and DI water.
[0126] TiO.sub.2 nanoparticle coating: Carboxylated titania nanoparticles with a diameter of 200 nm (1010 nanoparticles/ml, Microspheres-Nanospheres company) in water was firstly filtered using a centrifuge filter with a pore size of 1 ?m to remove the aggregated nanoparticles. Carboxylated TiO.sub.2 particles and amino-functionalized microdisks were separately dispersed in buffer solution (300 ?l). Buffer solution refers to MES aqueous solution (10 mM, pH=5). A microdisk solution was then added to the TiO.sub.2 particles solution with ultrasonic treatment and placed on a shaker for 5 minutes. A buffer solution (200 ?l) containing N-(3-dimethylaminopropyl)-N-ethylcarbodiimide Hydrochloride (EDC, 25 mg) and N-hydroxysuccinimide (NHS, 25 mg) was added and placed on a shaker for another 3 hours. Finally, the suspension of nanoparticle-coated microdisks was then transferred to a 1 ?m-pore centrifuge filter, and filtered thoroughly by at least five repeated cycles of centrifugation and resuspension (via ultrasonication) using DI water.
[0127] Effect of deep tissue scattering on angle-dependent collection efficiency.
[0128] In applications in which microdisk LPs are imaged deep within biological tissues, intrinsic scattering of light from the tissue itself may affect the angle-dependent collection efficiency of the LP. To investigate this phenomenon, an open-source Monte-Carlo simulation platform was used. By defining a directional emitter of the theoretical form |E.sub.far(?)|.sup.2=sin.sup.18(e) using custom C code, we were able to simulate disk emission for a variety of angles between ?=0 and ?=90?. The tissue scattering properties were chosen to be consistent with typical values for brain tissue at 1270 nm with a scattering coefficient ?.sub.s=72 cm.sup.?1 and anisotropy g=0.9. The absorption coefficient ?.sub.a=1.1 cm.sup.?1 was set to be that of water.
[0129]
[0130] The results are shown in
[0131] It will be appreciated by those skilled in the art that while the disclosed subject matter has been described above in connection with particular embodiments and examples, the subject matter is not necessarily so limited, and that numerous other embodiments, examples, uses, modifications, and departures from the embodiments, examples, and uses are intended to be encompassed by the claims attached hereto. The entire disclosure of each patent and publication cited herein is hereby incorporated by reference, as if each such patent or publication were individually incorporated by reference herein.
[0132] Various features and advantages are set forth in the following claims.