Raman spectrum detection method and system with sensitivity and response speed

Abstract

Most of existing Raman spectrum detection technologies are used for qualitative detection of substances, and since Raman scattering is 10-14 orders of magnitude smaller than Rayleigh scattering and 2-3 orders of magnitude smaller than fluorescence scattering, exciting light with large energy needs to be focused on a detected substance, and contradiction of sensitivity, response speed and generated damage exists in quantitative detection of living bodies. The method has the main innovation points that 1, the size and the position of an exciting light spot are controlled by adopting a control function, so that the injury to a living body is greatly reduced; 2, high-precision Raman spectrum data is collected by adopting point light spot long-time integration, precision Raman spectrum data is collected by adopting surface light spot short-time integration, and sensitivity and speed are considered by adopting a statistical and deep learning calibration function; 3, high-multiple scattered light energy is collected by adopting a condensation receiver so as to increase the detection sensitivity by two orders of magnitude; and 4, the system efficiency is optimized by adopting off-axis light paths of exciting light and scattered light. Embodiments of Raman spectroscopy detection for an in vitro diagnostic device (IVD) are provided.

Description

technical field [0001] The present invention relates to the field of optical metrology and laser biology, in particular to scattered light detection and sensors, especially to the method and system composition of Raman spectrum detection with both sensitivity and response speed, such as IVD (English) for non-invasive human body Name: In Vitro Diagnostic products, abbreviation: IVD, Chinese abbreviation: in vitro diagnostic products) in vitro blood glucose, hormone and other detection products. Background technique [0002] 1. Summary of key issues [0003] The traditional Raman spectrometer is usually used for qualitative measurement of detection substances, and it is rare for quantitative measurement or even for human detection. The reasons for this are: [0004] 1. Spot position problem [0005] Because the excitation light is irradiated with the detection substance in a focused way, the focused spot is very small. For the non-uniform detection substance, due to the lim...

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Problems solved by technology

In addition, for human body detection, the focused laser spot is more or less harmful to human tissue, especially for scenes that require continuous detection, the damage problem is more serious

[0006] 2. Resolution problem

[0007] Because Raman scattering accounts for a very small amount in all scattered light, according to information, Raman scattered light is 10 to 14 orders of magnitude smaller than Rayleigh scattered light, and 2 to 3 orders of magnitude smaller than fluorescence scattered light! Although people use filters to prevent Rayleigh scattered light with the same wavelength as the excitation light in the spectral light path, and use differential excitation light and its differential algorithm to eliminate fluorescence scattered light, the existing high-precision Raman spectrometer, although used for integration The AD converter usually uses 16bit, and the resolution can reach 1 / 65536, but its actual maximum resolution is far less than this order of magnitude. For the solution content, it is only 1%, and the glucose content in human venous blood In detection, its lowest concentration is about 0.04%, which is far beyond the resolution requirement

[0008] 3. Sensitivity problem

These solutions are not suitable for the detection of human body or living organisms, whether for skin or internal tissues, due to the large damage caused.

[0010] 4. Response speed problem

This is acceptable for low-speed measurements, but for high-speed measurements, such a sampling time cannot be supported

For example, if the pulse is used to verify the blood sugar value, since the pulse cycle is less than 1 second, and the integration time is greater than 10 seconds, it is impossible to verify the blood sugar value through the pulse

[0012] 5. Coaxial work problem

[0045] 1. An optical probe is only designed, and it is not proposed that the reflective cavity should be designed to converge the excitation light or scattered light to the light-concentrating receiver. At the same time, the content of the invention and the embodiments have never proposed the problem of converging scattered light energy to improve detection sensitivity

[0046] 2. The emission of incident light and the reception of scattered light only adopt the coaxial method, not the off-axis method, which results in the inability to realize the independent design of the light-condensing receiver lens, so that the function of collecting scattered light cannot be realized

[0049] 1. The entrance angle of the focused light of CPC is small, the maximum limit is no more than ±30 degrees, and the hemispherical angle of ±90 degrees of scattered light cannot be achieved.

[0050] 2. The angle of light focused at the bottom of the CPC is too large. Due to the small critical angle of total reflection of the optical fiber, the actual effective concentration ratio is not high, and the concentration contribution rate is small

[0051] 3. The axial length of CPC is too large, which is not conducive to the miniaturization of components

[0060] 1. The excitation light method in the form of focused spot is more harmful to living tissue and is not suitable for living body detection

[0061] 2. Can not take into account the measurement sensitivity and response speed

[0062] 3. The maximum sensitivity of the current Raman spectroscopy detection method for mixed substances is only 1%, which is too low to complete the detection of ultra-low and ultra-trace levels

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