Compressive sensing for mid-infrared spectroscopy & imaging

Abstract

In at least one example of the present disclosure, a device can include a sample stage configured to hold a sample, pulsed laser source configured to produce a pulsed light in the mid-infrared (IR) region, and a polarizer configured to receive the pulsed light. The device can further include a plurality of optical components, an active multiplexing device (AMD), a detector configured to receive the pulsed light, and a data processing unit configured to generate an image.

Description

COMPRESSIVE SENSING FOR MID-INFRARED SPECTROSCOPY& IMAGINGCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit of priority pursuant to 35 U.S.C. § 119(e) of US. provisional patent application No. 63 / 689,540 entitled “COMPRESSIVE SENSING FOR MID-INFRARED SPECTROSCOPY & IMAGING,” filed on August 30, 2024, which is hereby incorporated by reference in its entirety.FIELD

[0002] The described embodiments relate generally to microscope systems, and more particularly, to a microscope for obtaining a mid-infrared (IR) absorbance and circular dichroism (CD) spectroscopic image.BACKGROUND

[0003] Uncovering extraterrestrial life within the Solar System is profoundly shaped by our understanding of terrestrial biology and its distinctive biosignatures. A key characteristic of all known life on Earth is homochirality. Homochirality is the exclusive presence of left-handed (L) amino acids and right-handed (D)sugars. Chirality is a fundamental property in myriad, biological and chemical processes, ranging from the regulation of metabolic pathways to molecular recognition, enzymatic activity, and maintaining structural integrity of the molecules. It is u niversally acknowledged as a critical element for the inception or initial evolution of life. Interestingly, analyses of meteorites have shown varying L-enantiomeric excesses, hinting at prebiotic chiral influences. In stark contrast bacteria utilize both L and non-proteinogenic D-amino acids, crucial for constructing bacterial biomolecules and contributing to organic material in deep ocean waters. This distinctive chirality in biological versus non-biological materials underscores the importance of chirality as a biosignature. Consequently, large L- or D- enantiomeric excesses in chiral amino acids and sugars stands as a compelling marker for the presence of current or past life on other planets or meteorites or comets . However, due to the complexities involved in in-situ analysis of complex organics inextraterrestrial contexts, returning samples to Earth has been the predominant method fpr validating the origins of chiral asymmetry and identifying other potential biosignatures. The applications of chiral imaging extend beyond astrobiology and hold significant promise in the fields of histopathology and pharmacology . Vibrational Circular Dichroism (VCD) spectroscopy can determine the absolute configuration of chiral molecules as well as identify macromolecules such as collagen, amyloid fibrils, and DNA. This capability is crucial for disease detection; for instance, the misfolding and aggregation of specific proteins, detectable through chiral imaging, can indicate neurodegenerative diseases such, as Alzheimer’s. Moreover, chiral imaging not only facilitates disease detection but also enables the monitoring of treatment efficacy. thereby providing a valuable platform for evaluating drag performance. Given that over 50% of marketed drugs am chiral compounds. where enantiomers can possess identical chemical stractures but exhibit different pharmacological, toxicological, arid pharmacokinetic profiles, VCD spectroscopy plays a vital role in. drag safety and development.

[0004] Compared to terrestrial techniques for chirality sensing, only a handful of current device technologies have been validated for space use. Traditional methods, such as mass spectrometry, are effective in identifying simple organic compounds but lack the capability to deliver spatially-resolved chirality information for structurally complex molecules like carbohydrates and lipids. Current mid-IR imaging systems can experience challenges, such as low signal-to-noise ratios (SNR) mid prolonged acquisition times that are exacerbated by scanning across broad bandwidths. Therefore, there is a need for a device offering a refined solution for prec ise, fo situ, spatial imaging of chirality with a high SNR and shorter acquisition times.SUMMARY

[0005] Disclosed herein may be a device including a sample stage configured to hold a sample, pulsed laser source configured to produce a pulsed light in the mid- infrared (IR) region, and a polarizer configured to receive the pulsed light. The device can further include a plur ality of optical components, an active multiplexing device (AMD), a detector configured to receive the pulsed light, and a data processing unit configured to generate an image. In one example, the sample stage defines an aperture, wherein the aperture of the sample stage configured to allow the pulsed light to pass through the thickness of the sample stage. The plurality of the optical components can include a beam expander, a mirror, and a beam splitter. The device can further include a photoelastie modulator (PEM), wherein the PEM configured to convert a linear polarization of the pulsed light to a right-handed and left-handed polarized state. In one example, the pulsed laser source including a quantum cascade laser (QCL). The detector including a photovoltaic immersion mercury cadmium telluride defector (PVI MCT). In one example, the AMD including a digital micromirror device (DMD). In another example, the detector further including a Vibrational Circular Dichroism (VCD) signal detector. The device further including a second detector, wherein the second detector including a reference detector. The device can finther include a second stage configured to translate the sample stage relative to the pulsed laser source.

[0006] Also disclosed may be a microscope for obtaining a mid-IR absorbance can circular dichroism (CD) can include a sample stage configured to hold a sample, and the stage defining an aperture. Tire microscope further including a quantum cascade laser (QCL ) configured to produce a pulsed fight, a polarizer configured to receive the pulsed light, a DMD, and a PEM. The inicroscope further including a beam splitter configured to split the pulsed light into a first pulsed light and a second pulsed light, a first detector configured to receive the first pulsed light, and a second detector configured to receive the second pulsed light. The: microscope including a, data processing mrit configured to generate an image based on the first pulsed light received by the first detector and the second pulsed light received by the second detector . In one example, the QCL configured to produce a pulsed light producing a light within a 3-13 micrometer wavelength. Thefirst detector including a VCD signal detector, and the second detector including a reference: detector. The fest detector and fee second detector including a PVI MCT. The aperture o f fee sample stage can be configured to allow the pulsed light to pass through the thickness of fee sample stage, The PEM configured to convert the linear polarization of fee pulsed light to a right-handed and left-handed polarization state;

[0007] In another aspect, a method is disclosed, the method including, producing a pulsed light in the mid-IR region with a specific pulse repetition rate, directing the pulsed light toward an AMD, and transmitting the pulsed light to a sample stage and a sample. The mefeod including splitting fee pulsed, light into a first pulsed light and a second pulsed light, and collecting the first pulsed light into a first detector and a second pulsed light into a second detector. The method further including processing the first pulsed light and fee second pulsed light data, and generating an image of the sample surface. In one example, the method including traversing fee pulsed light about fee sample stage, modulating a linear polarization of the pulsed light into a righ t-handed and left-handed polarized state . The method further including detecting the change in the absorption of feeright-handed versus fee left-handed circularly polarized light, calculating the VCD of the detected changes, and generating an image of the sample surface including detecting fee changes of the calculated VCD.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The disclosure will be readily understood by the following detailed description in conjunction with the accompanying drawings. wherein like reference numerals designate like structural elements, and in which:

[0010] FIG. 1 illustrates a perspective view of one example of the device;

[0011] FIG. 2 illustrates a perspective view of one example of the device:

[0012] FIG. 3 illustrates a comparison of current technologies image generation versus one example of image generation of the device; and

[0013] FIG. 4 illustrates a flowchart of generating an image on one example of the device.

[0014] DETAILED DESCRIPTION

[0015] The disclosed instruments, systems, md methods introduce a revolutionary leap in measurement technology, engineered for the nondestructive, rapid, in-situ capture of spatial absorbance and chirality data, some factors useful in identifying chemical composition and enantiomeric excess, respectively, relevant for biosensing applications. Possible samples for analysis using: the disclosed instruments, systems, and methods vary from complex biological matriees such as stromatolites, and endolithic bacteriaVarchaeal communities within the pore spaces of rock to proteins, and chiral drugs.

[0016] The disclosed instruments, systems, and methods transcend limitations of existing technology, offering refined solutions, which may be tailored for precise, in-situ spatial imaging of chirality. The disclosed technology may be particularly usefill at uncovering prebiotic chemistry and understanding evolutionary dynamics on potentially habitable planetary bodies. The proposed instruments, systems, and methods may, in many embodiments , integrate mid-infrared chiral imaging, in one example utilizing an active multiplexing device such as digital micromirror device (DMD), a quantum cascade laser (QCL) source, and single-pixel detection techniques. In many embodiments, the disclosed instruments, systems, and methods may span a broad spectral range, for one example a range of about 3-13 μm, in other embodiments the spectral range may be somewhat larger or broader. The disclosed configruatians may help to overcome challenges posed by traditional Vibrational Circular Dichroism (VCD) technique, including low signal-to-noise ratios (SNRs), low sensitivity , and / or limited spatial resolution, In one embodiment, this may be accomplished by exploiting the unique advantages of QCL-based VCD spectroscopy for high-precision chirality imaging.

[0017] The disclosed instruments, systems, and methods may, in some cases, be distinguished by their ability to operate across multiple contrast mechanisms, which may be invaluable for analyzing both structural and fonctional chracteristics of cells, especially in diverse applications from space exploration to terrestrial medical pathology. The disclosed instruments, systems, and methods provide for adaptable operational modes. Adaptable operational modes may, in many embodiments, allow comprehensive analyses of both liquid and solid samples, enhancing applicability to a range ofextraterrestrial and terrestrial environm ents, such as the icy moons of Enceladus and Europa or the rocky landscapes of Mars . Additionally, die versatile capabilities of these:technologies may be particularly useful for studying microscopic, localized changes in tissue, thus extending tile broad applicability of the present instruments, systems, and methods to disease detection and identification.

[0018] Applican' s development of the presently disclosed instruments, systems, and methods offer various benefits including, but not limited to: fl) significantly advancing life detection technologies, while adhering to the NASA Astrobiology Roadmap by acquiring multiple distinct biosignatures for a robust assessment of potential life, and (2) advancing mid-IR imaging technologies, facilitating fogh-resolution, rapid, and comprehensive spectroscopic analysis: of biological samples, thereby driving progress in histopathology, immunology, and phamiacology'.

[0019] Applicant's disclosed instruments, systems, and methods stand at the forefront of extraterrestrial biosignature and terrestrial disease detection, by, for example, integrating absorbance imaging with high-precision chiroptical spectroscopy. Applicant’s disclosure extends beyond bulk enantiomeric analysis to provide spatial distribution of chirality -- a fundamental indicator of life - the disclosed instruments, systems and methods equip Users to probe the nuances of habitable enviroments and human physiology.

[0020] The disclosed instruments , systems, and methods offer unmatched spatial sensitivity and non-des tractive analysis capabilities, while greatly surpassing existing technologies like ChiralSpec, GC-MS, and MILA. Applicant’s disclosed technology effectively handles a wide range of chemical compositions, including, without limi tation amino acids and carboxylic acids (two key biom arkers of extant life) and those in aqueoussolutions, often found in space environments.

[0021] The lack of effecti ve tools for site-specific chirality imaging necessitates innovative solutions. Addressing existing challenges in acquisition speed, and spatial resolution, may enable precise extraction of scientifically significant parameters like sample chirality. Leveraging prior advancements in chirality imaging, Applicant’s technology demonstrates capabilities beyond traditional mid-infrared vibrationalspectrometers (both absorbance and circular dichroism) to enable imaging. Instead of using a mechanical scanning system to enable imaging that is common with tabletop microscope designs. Applicant’s innovation is based on an implementation design by integrating either a passive or an active multiplexing device (for example, a digital micromirror device, spatial light modulator and any other devices) to enable single- element detection with structured illumination in the mid-IR regime for both absorbance and chirality mapping via VCD.

[0022] The disclosed instruments, systems, and methods possess a unique capability to visualize high-resolution (~2 μm at λ = 3 μm) chirality maps, an achievement that is surprisingly beyond the reach of current techniques. Furthermore , the disclosed instruments, systems, and methods bypasses the need for large moving components, like stages in conventional raster scanning microscopes, by adopting structured ilumination and single-pixel detection strategies. Ibis streamlines the disclosed system’s arChitectiire, paving the way for additional miniaturization , while enhancing its reliability and sfiudiness, making it exceptionally well-suited for the rigors of space exploration.

[0023] Reference will now be made in detail to representative embodiments, including embodiments illustrated in the accompanying drawings. It should be understood that the descriptions presented herein are not intended to limit the embodiment to one preferred embodiment. To the contrary, it is intended to cover alternatives, modifications, and equivalents as can be included within the spirit and scope of the described embodiments as defined by the appended claims.

[0024] The following disclosure relates to an imaging device, more specifically to a mid- infrared (IR) spectroscopy imaging device. Mid-IR imaging is pivotal m detecting biological samples with unique spectra fingerprints. Mid-IR spectroscopy is an analytical technique used to identify funtion gmups and typical bonds of organic molecules by analyzing the vibrations associated wi th them in the mid-IR region of the electromag neticic spectrum. Mid-IR can most commonly be between 2.5 μm-15 μm Current mid-IR imaging systems can experience challenges, such as low signal-to-noise ratios (SNR) and prolonged acquisition times that are exacerbated by scanning across broad bandwidths. However, traditional methods, such as mass spectroscopy, are limited to identifyingsimple organic compounds. Vibrational Circular Dichroism (VCD) spectroscopy measures spatially resolved chirality data that is essential for observing stmctaally complex molecules like carbohydrates and lipids.

[0025] The present disclosure introduces a system that integrates mid-IR absorbance and Circular dichroism (CD) imaging, enabling multiple measurement modalities. The disclosed method and device overcome traditional mid-IR systems challenges by incorporating sparce signal recovery, that significantly reduces the number of measurements required while maintaining a high SNR, therefore increasing the efficiency, performance, and versatility or biological applications.

[0026] In at least one example, a device for creating a mid-IR absorbance and CD spectroscopic image can include a sample stage configured to hold a sample. In one embodiment, the sample can be an enantiomeric sample, wherein the chirality arises from molecular or structural conformations. In one example, the stage can define an aperture, such that the aperture can allow light to pass through the sample stage. The quantum cascade laser (QCL) can be configured to produce a pulsed light The device can further include a polarizer, a digital micromirror device (DMD) and a photoelastic modulator (PEM). In this way, the a PEM can convert a linear polarization of the pulsed light to a right-handed and a left-handed polarized state. In one example, a beam splitter of the device can slit he pulsed light into a first pulsed light and a second pulsed light. In this example, the device can include a first detector and a second detector, such that a fest pulsed light can be received by a fest detector and a second pulsed light can be received by a second detector. A data processing unit can be configured to generate an image based on the first pulsed fight received by the first detector and the second pulsed light received by the second detector. The device configured to include a DMD can be advantageous as its part of the sparse signal recovery strategies to increase the SNR and lower acquisition time .

[0027] In at least one example, a method of generating an image from nfid-IR absorbance and CD spectroscopic imaging disclosed herein. The method including, providing a pulsed light in the mid-IR. region with a specific pulse repetition rate, anddirecting the pulsed light toward an AMD. From the AMD the pulsed light can bedirected toward a beam, splitter configured to slit the pulsed light into a first pulsed light and second pulsed, light. The first pulsed light can be transmitted to a sample stage and a sample. The pulsed light can tr averse through the sample and the sample stage and collect the first pulsed light into a first detector. The second pulsed light can he refracted by a mirror and directed into a second detector. In one example, the data of the first pulsed light and the second pulsed light can be processed in such a way to generate an image of the sample surface. This method can be advantageous as the method is configured to increase the SNR and lower the acquisition time.

[0028] These and other examples are discussed below with reference to FIGS. 1 through 4. However, those skilled in the art will readily appreciate that the detailed description given herein with respect to these Figures is for explanatory purposes only and should not. be construed as limiting. Furthermore as used herein, a system, a method, an article, a component, a feature, or a sub-featare including at least one of a first option, a second option, or a third option should be understood as referring to a system, a method, an article, a component, a feature, or a sub-feature that can include one of each listed option (e.g., only one of the first option, only one of the second option, or only one of the third option), multiple of a single listed option (e.g., two or more of the first option), two options simultaneously (e.g. , one of the first option and one of the second option), or combination thereof (e.g,, two of the first option and one of the second option).

[0029] FIG. 1 illustrates a perspective view of one example of the device 100. The device 100 can include a sample stage 102 that can be configured to hold a sample, not illustrated in FIG. 1 . In one example, the sample can be an enantiomeric sample. In at least one example, the sample Stage 102 can define an aperture 103. Tire device 100 can include a pulsed laser source 104 that can be configured to produce a pulsed light in the mid-IR region with. a specific pulse rate. The pulsed laser source 104 can inc lude to be a semiconductor laser such as an edge emitting laser, vertical-cavity surface-emitting laser, a quantum cascade laser, an interband cascade laser, a tunable coherent laser, a. fiber laser, or the like. In one example, the pulsed laser source 104 can produce a pulsed light producing a light within a 3- 13 μm wavelength. In at least one example, the device 100 can further include a second stage, not illustrated in FIG. L such that the second stage isconfigured to translate the sample stage 102 relative to the pulsed laser source 104. The device 100 can include a polarizer 106 configured to receive the pulsed light fiom the pulsed laser source 104. la one example, a polarizer 106 can be an optical filter that lets light waves of specific polarization pass through while blocking light waves of other polarizations, A& the pulsed light .passes through the polarizer 106, the pulsed light can pass through a beam expander 108, In one example, foe beam expander 108 can take the pulsed light and expand the width of the pulsed light.

[0030] In the embodiment shown in FIG. 1, as the pulsed light is expanded via the beam expander 108 the light can reflect from a mirror 110. In one example, the minor 110 can include a rotatable mirror, a beam-steering mirror, rotating prisms, piezoelectric oscillators, or any Suitable optical component to adjust the pointing angle of the pulsed light. In one example, the mirror 110 can direct the pulsed light into an active multiplexing device (AMD) 112. In one example, the AMD 112 can include a digital micromirror device (DMD), a spatial tight modulator, a timable filter, or the like . In one example, the AMD 112 can include a DMD, as illustrated in FIG . 2, such that the DMD can provide an array of microminrcsrs that can be articulated, and tire DMD can enable structured illumination of the sample using binary (on / off) pixelated patterns for collecting both absorbance and VCD images.

[0031] In one example, the device 100 can include a polarization modulator 114. The polarization modulator 114 can transform a linear polarization into a right-handed and left-handed circularly polarized states that are oscillating at a specified modulating fiequency through augmentation. In one example, the polarization modulator 114 can including a photoelastic modulator (PEM), as illustrated in FIG. 2, an acousto-optic, and electro-optic, a Berek tunable waveplates, or the like, in another example, more modulation techniques can include intensity, phase, or spatial tight modulation. As the pulsed light travels from the AMD 112 through the polarization modulator 114 and can enter a beam splitter 116. The beam splitter 116 can split the pulsed light into a fast pulsed light 117 and a second pulsed light 119.

[0032] In one example, the first pulsed li ght 117 can exit the beam splitter 116 and interact with the sample stage 102 and the sample. As illustrated in FIG. 1, the first prisedlight 117 can enter the aperture 103 and travel through the thickness of the sample stage 102. As the first pulsed light 117 exits the sample stage 102 it can then interact with a convex lens 121 as to focus the first pulsed light 117. The device 100 can include a first detector 118. Thefocused first pulsed light 117 can be received by the first detector 118. The device 100 can further include a second detector 120. In one example, as the second pulsed light 119 exits the beam splitter 116 it can be adjusted by a mirror to be directed into the second detector 120. In one example the first detector 118 and the second detector 112 can include a photovoltaic immersion mercury cadmium telluride detector (PVI MCT), a Schotky barrier detector, a platinum silicide detector, a gallium indium antimonide strain layer superlattices detector, a Side heterojunction detector, or any suitable detector. In one example, the first detector 118 comprises a VCD signal detector and the second detector 120 comprises a reference detector. In at least one example, the device 100 can further include a data processing unit 122 configured to generate an image based on the first pulsed light 117received by the first detector 118 and the second pulsed light 119 received by the second detector 120.

[0033] FIG. 2 illustrates a perspective view of one example of the device 200. The device 200 can include a similar layout and components such as the device 100, of FIG.1, discussed above. For example, the device 200 includes a sample stage 202, a pulsed laser source 204, a polarizer 206, a mirror 110, an AMD 112 illustrated as a DMD in FIG.2, a PEM 114, a beam splitter 116, a fest and second detectors 218, 220, and a da ta processing unit 222. As illustrated in FIG. 2, the device 200 does not include a, beam expander 108, as illustrated in FIG. 1 . In at least one example, the device 200 can include an Objective lens 224to focus a pulsed light form a pulsed laser source 204, In this way, the pulsed light can raster across a sample with the focused pulsed .light rather fen the fight cover the entirety of the Sample, as illustrated in FIG; 1. The device 200 can further include a convex lens 226 such that the fecused light leaving the sample stage 202 can be expanded.

[0034] FIG. 3 illustrates a comparison of current technologies image generation versus one example of image generation of the device. As illustrated by FIG. 3, the first image 301 can be an original image captured. The acquisition time can be longer as its based ona traditional method of collecting and generating an linage. The second image 303 can illustrate a reconstructed image with 20% of the measurements as compared to the fest image 301. For an image generated such as illustated in the second image 303, the acquisition time can be 50x fester than collecting the original image. The graph 305 can illustrate the modulation transfer curves for original and reconstructed images from 20% of measurements with 50x faster acquisition rate.

[0035] FIG. 4 illustrates a flowchart 400 of generating an image on one example of the device. The method can include producing a pulsed light in the mid-IR region with a specific pulse repetition rate (Block 402). In this way, a pulsed light can be produced by a QCL 104 , as illustrated in FIG. 1. The method can include directing the pulsed light toward an AMD (Block 404). The pulsed light can be directed by the minor 110 illustrated in FIG . 1, The pulsed light can be transmitted to the sample stage and a sample (Block 406). In at least one example, the method can further include traversing the pulsing light about the sample stage, such as the light can raster about the sample. In one example, the method can include modulating a linear polarization of the pulsed light to a right-handed and a left-handed circularly polarized light. The pulsed light can then be split into a fest pulsed light and a second pulsed light via a beam splitter (Block 408). The first pulsed light can be directed to a first detector and the second pulsed light can be split from, the beam splitter to a second detector (Block 410). In this way, the first detector comprises a VCD signal detector and the second detector comprises a reference detector. Tire method further comprising processing the first pulsed light and the second pulsed Iight data from the first and second detectors (Block 412). The method can further include detecting change in absorption of the right-handed versus the left-handed circularly polarized light and calculating the VCD of the detected changes. In this way, the method can further include generating an image of the sample surface from the first pulsed light received in the first detector arid the second pulsed light received in the second detector (Block 414).

[0036] The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the described embodiments. However, it will be apparent to one skilled hi the art that the specific details are notrequired in order to practice the described embodiments. Thus, the foregoing descriptions of the specific embodiments described herein are presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the embodiments to the precise forms disclosed. It. will be apparent to one of ordinary skill in the art that many modifications and variations are possible in view of the above teachings

Claims

CLAIMSWhat is claimed is:

1. A device, the device: comprising: a sample stage configured to hold a sample; a pulsed laser source configured to produce a pulsed light in the mid- infrared (IR) region; a polarizer configured to receive the pulsed light; a plurality of optical components; an active nmltiplexing device (AMD); a detector configured to receive the pulsed light; and a data processing unit configured to generate an image.

2. The device of claim 1 , wherein the sample stage defines an aperture.

3. Die device of claim 2. wherein the aperture of the sample stage configured to allow the pulsed light to pass through the thickness of the sample stage.

4. The device of any one of claims 1-3, wherein the plurality of optical components include: a beam expander: a mirror; and a beam splitter.

5. The device of any one of claims 1 -4, further including a photoelastic modulator (PEM).

6. The device of claim 5, wherein the PEM configured to convert a linear polarization of the pulsed light to a right-handed and a left-handed polarized, state.

7. The device of any one of claims 1-6, wherein the pulsed laser source comprises a quantum cascade laser (QCL).

8. The device of any one of claims 1-7, wherein the detector comprises a photovoltaic immersion mercury cadmium telluride detector (PVI MCT).

9. The device of any one of claims 1-8, wherein the AMD comprises a digital micromirror device (DMD).

10. The device of any one of claims 1-9, wherein the detector comprises a Vibrational Circular Dichroism (VCD) signal detector.

11. The device of any one of claims 1 -10. further comprising a second detector,12. The device of claim I I, wherein the second detector comprises a reference detector.

13. The device of any one of claims 1-12, further comprising a second stage configured to translate the sample stage relative to the pulsed laser source,14. A microscope for obtaining a mid-infrared (IR) absorbance and circular dichroism (CD) spectroscopic image, the microscope comprising: a sample stage configured to hold a sample, the stage defining an aperture; a quantum cascade laser (QCL) configured to produce a pulsed fight; a polarizer configured to receive the pulsed light; a mirror; a digital micromirror device (DMD); a photoelastic modulator (P.EM). a beam splitter configured to split the pulsed light into a first pulsed light and a second: pulsed fight; a first detector configured to receive the first pulsed light; a second detector configured to receive the second pulsed light; anda data processing unit configured to generate an image based on the first pulsed light received by the first detector and the second pulsed light received by the second detector.

15. The microscope of claim 14, wherein the quantum cascade laser configured to produce a pulsed light producing a light within a 3-13 micrometer wavelength.

16. The microscope of any one of claims 14-15, wherein: the first detector comprises a Vibrational Circular Dichroism (VCD) signal detector; and the second detector comprises a reference detector.

17. The microscope of claim 16, wherein the first detector and the second detector comprising a photovoltaie inversion rnercury cadmium telluride detector (PVI MCT).

18. The microscope of any one of claims 14-17, wherein the aperture of the sample stage configured to allow the pulsed light to pass through the thickness of the sample stage.

19. The microscope of any one of claims 14-18, wherein the PEM configured to convert a linear polarization of the pulsed fight to a right-handed and a left-handed polarized state.

20. A method, the method comprising: producing a pulsed fight in tire mid-infrared (IR) region with. a specific pulse repetition rate; directing the pulsed light toward an active multiplexing device (AMD); splitting the pulsed light into a fest pulsed light and a second pulsed fight; transmitting the pulsed light to a sample stage and a sample; collecting the first pulsed light into a first detector and a second pulsed light into a second detector; processing the first pulsed light and the second pulsed light data; and generating an image of the sample surface.

21. The method, of claim 20, further comprising traversing the pulsed light about the sample stage.

22. The method of claim 21 , further comprising modulating a linear polarization of the pulsed light to a right-handed and a left-handed polarized state.

23. The method of claim 22, further comprising detecting the change in the absorption of the right-handed versus the left-handed circularly .polarized light.

24. The method of claim 23, further comprising calculating the Vibrational Circular Dichroism (VCD) of the detected changes.

25. The method of claim. 24, wherein the generating an image of the sample surface further comprises detecting the changes of the calculated VCD.

Images