A single particle spectroscopy system comprising: differential numerical aperture optics for emitted and scattered light; at least one quantum cascade laser source 102, wherein the at least one QCL source 102 is configured to deliver light to the single particle to thereby induce resonant mid-infrared absorption in the particle or in an analyte within the particle; wherein the differential numerical aperture optics focus the light from the at least one QCL source 102 through the single particle resulting in an illumination pattern; a handling system 118 that presents a single particle to the at least one QCL source 102; a mid-infrared detection facility 104 for detecting the transmitted mid-infrared wavelength light and scattered mid-infrared wavelength light from the particle; and a processor configured to determine a characteristic of the particle based on the transmitted mid-infrared wavelength light and scattered mid-infrared wavelength light from the particle, characterized in that: the handling system 118 comprises a manifold or a microfluidic flow architecture, the handling system 118 includes a carrier substrate in which the single particle is disposed for presenting the single particle to the at least one QCL source 102, the characteristic of the particle is selected from the group consisting of chemical composition, shape, size, volume, density, orientation, position, velocity, and a combination thereof. differential numerical aperture optics for emitted and scattered light; at least one quantum cascade laser source 102, wherein the at least one QCL source 102 is configured to deliver light to the single particle to thereby induce resonant mid-infrared absorption in the particle or in an analyte within the particle; wherein the differential numerical aperture optics focus the light from the at least one QCL source 102 through the single particle resulting in an illumination pattern; a handling system 118 that presents a single particle to the at least one QCL source 102; a mid-infrared detection facility 104 for detecting the transmitted mid-infrared wavelength light and scattered mid-infrared wavelength light from the particle; and a processor configured to determine a characteristic of the particle based on the transmitted mid-infrared wavelength light and scattered mid-infrared wavelength light from the particle, characterized in that: the handling system 118 comprises a manifold or a microfluidic flow architecture, the handling system 118 includes a carrier substrate in which the single particle is disposed for presenting the single particle to the at least one QCL source 102, the characteristic of the particle is selected from the group consisting of chemical composition, shape, size, volume, density, orientation, position, velocity, and a combination thereof. the handling system 118 comprises a manifold or a microfluidic flow architecture, the handling system 118 includes a carrier substrate in which the single particle is disposed for presenting the single particle to the at least one QCL source 102, the characteristic of the particle is selected from the group consisting of chemical composition, shape, size, volume, density, orientation, position, velocity, and a combination thereof.