A microarray spectral scanning analysis system based on spatiotemporal continuous temperature gradient

Abstract

This invention discloses a microarray spectral scanning analysis system based on a spatiotemporally continuous temperature gradient, belonging to the fields of spectral analysis and precision automation technology. It includes a sample reservoir, a sample cell, a sample introduction module, a temperature control module, an optical path module, a motion device, and a spectral detection and analysis unit. The sample cell corresponds to the outlet end of the sample introduction module and serves as a sample carrier accessory for detection. The sample introduction module establishes the sample introduction relationship between the sample cell and the sample reservoir by closing or opening one or more channels, or by spotting or injecting samples. The temperature control module uses real-time or time-sharing detection during temperature increase. The spectral detection and analysis unit is used for axial scanning detection relative to the sample cell. This invention can, with the aid of a single device, simultaneously or almost simultaneously measure three spectral characteristics of the sample, including any combination of light scattering, fluorescence, and absorbance. Furthermore, it can obtain information such as molecular interactions, stability, particle size, dispersion, aggregation, and viscosity through mathematical models or calculations.

Description

Technical Field

[0001] This invention relates to the field of optical scanning technology, specifically a microarray spectral scanning analysis system based on a spatiotemporal continuous temperature gradient. Background Technology

[0002] Microfluidics (chip) technology is a rapidly maturing technology that has been successfully commercialized in various sub-fields, such as digital PCR instruments, protein chips, nucleic acid chips, and cell sorting. Microfluidics integrates basic operational units of biological, chemical, and pharmaceutical sample preparation, reaction, separation, and detection onto a micrometer-scale chip, automating the entire analytical process. It is a scientific technology characterized by the manipulation of fluids at the micrometer scale, also known as a laboratory-on-a-chip. Sample separation and mixing, as well as high-sensitivity spectral detection, represent a significant application potential of microfluidics. Currently, drug screening primarily utilizes compound or small molecule library screening, molecular simulation, fluorescence detection technology, flow cytometry, molecular interaction techniques, and other molecular analysis methods. While these methods are diverse, their inherent limitations restrict their application to a wide range of samples and conditions, including throughput, cost, sensitivity, and unsuitability for large-volume samples. Furthermore, they are influenced by the size, conformational sensitivity, and solution environment of different drug molecules. Summary of the Invention

[0003] The purpose of this invention is to provide a microarray spectral scanning analysis system based on a spatiotemporal continuous temperature gradient to solve the problems in the background art.

[0004] To achieve the above objectives, the present invention provides the following technical solution: A microarray spectral scanning analysis system based on a spatiotemporally continuous temperature gradient includes a sample reservoir, a sample cell, an injection module, a temperature control module, an optical path module, a motion device, and a spectral detection and analysis unit. The sample reservoir corresponds to the inlet of the injection module and is used for sample preparation. The sample cell corresponds to the outlet of the injection module and is used as a sample carrier accessory for detection. The injection module establishes the injection relationship between the sample cell and the sample reservoir by closing and opening one or more channels (including but not limited to miniature one-way valves). The temperature control module establishes a continuous temperature gradient for the micro-region sample in the sample cell through real-time detection during temperature increase. The optical path module performs optical detection on the micro-region sample in the sample cell using single or combined methods of fluorescence, dynamic and static light scattering, and absorption light detection. The motion device is used for the corresponding interaction between the sample reservoir and the sample cell. The spectral detection and analysis unit is used for axial scanning detection relative to the sample cell, and analyzes the changes of the sample with environmental conditions or different treatments based on the micro-region characteristics of the sealing liquid-sample-sealing liquid.

[0005] Based on the above technical solutions, the present invention also provides the following optional technical solutions: In one alternative: the sample introduction module can introduce samples manually or semi-automatically via injection or negative pressure. Alternatively, for axially non-closed sample cells, the sample and isolation liquid can be injected point by point or multiple points simultaneously via pipetting or injection to achieve sample arrangement. The sample cell with multiple micro-area arrays can be loaded into the instrument for detection manually or automatically.

[0006] In one alternative: the sample cell is circular or square; the inner length of the sample cell is preferably no more than 200 mm; the sample cells are arranged in a straight line, a ring, or other shapes.

[0007] In one alternative: the optical path module includes a light source and a detector, wherein the light source is one of LED, laser or composite spectrum, and the wavelength is 200-400nm or 500-900nm, or a single or multiple wavelength band combination; the detector is a single or combined type detector of PMT, APD, CMOS and CCD.

[0008] In one alternative: the dynamic and static light scattering illumination unit is a laser; the fluorescent illumination unit is an LED or a laser; and the absorption light detection preferably uses a composite spectrum illumination unit.

[0009] In one alternative: the spectral detection and analysis unit can also obtain the changes in spectral information of the sample with respect to the environment or different treatments based on the change in the peak value of the signal.

[0010] In one alternative: the spectral detection and analysis unit also reflects changes in the properties of the sample by detecting changes in fluorescence and / or absorption light as the sample environment or different treatments change.

[0011] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. The sample cell in this invention can perform spectral analysis of time-temperature gradients and continuous spatial temperature gradients, and the establishment and utilization of continuous spatial temperature gradients to obtain temperature values; the high light transmittance and high openness of a sample cell spatial structure can be used to obtain spectral analysis with multiple functions. 2. Array scanning is used to obtain the signal mobility-concentration-time-space relationship by observing the changes in sample migration with temperature, and further to obtain the characteristics of the sample and / or interaction characteristics; 3. The present invention can use a single device to simultaneously or almost simultaneously measure three spectral characteristics of a sample, including any combination of light scattering, fluorescence, and absorbance, and further obtain information such as molecular interactions, stability, particle size, dispersion, aggregation, and viscosity through mathematical models or calculations. Attached Figure Description

[0012] Figure 1 This is a schematic diagram of the system framework structure in one embodiment of the present invention; Figure 2 This is a schematic diagram of the optical principle of a laser particle size analyzer. Figure 3 This is a diagram illustrating the principle of dynamic light scattering. Figure 4 This is a schematic diagram of the excitation and fluorescence emission process of molecules; Figure 5 This is a schematic diagram of the scattering signal from mixed particles. Figure 6 This is a schematic diagram of dynamic light scattering. Figure 7 This is a schematic diagram of a single sample cell structure; Figure 8 This is a schematic diagram showing the arrangement of multiple sample cells; Figure 9 This is a schematic diagram of the sample cell detection. Detailed Implementation

[0013] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. In the drawings or description, similar or identical parts are referred to by the same reference numerals, and in practical applications, the shape, thickness, or height of each component may be enlarged or reduced. The embodiments listed in this invention are merely illustrative and not intended to limit the scope of the invention. Any obvious modifications or changes made to this invention do not depart from the spirit and scope of the invention.

[0014] In one embodiment, such as Figure 1 As shown, a microarray spectral scanning analysis system based on a spatiotemporally continuous temperature gradient includes a sample reservoir, a sample cell, an injection module, a temperature control module, an optical path module, a motion device, and a spectral detection and analysis unit. The sample reservoir corresponds to the inlet of the injection module and is used for sample preparation. The sample cell corresponds to the outlet of the injection module and is used as a sample carrier accessory for detection. The injection module establishes the injection relationship between the sample cell and the sample reservoir by closing or opening one or more channels. The temperature control module establishes a continuous temperature gradient for the micro-region sample in the sample cell by real-time or time-sharing detection during temperature increase. The optical path module performs optical detection on the micro-region sample in the sample cell using single or combined methods of fluorescence, dynamic and static light scattering, and absorption light detection. The motion device is used for the corresponding interaction between the sample reservoir and the sample cell, and also for spectral detection of the micro-region in the sample cell. The spectral detection and analysis unit is used for axial scanning detection relative to the sample cell, and analyzes the changes of the sample with the environment or different treatments based on the micro-region characteristics of the sealing liquid-sample-sealing liquid.

[0015] In one embodiment, such as Figure 1As shown, the sample injection module can be used manually or semi-automatically via injection or negative pressure to inject the sample, and the sample cell with multiple micro-area arrays can be loaded into the instrument for detection manually or automatically. In one embodiment, such as Figure 1 As shown, the sample cell is preferably suitable for molecular experiments, with a small inner diameter or inner side length (not greater than 3 mm), preferably square or circular, and further can be other shapes such as polygons; the length and outer diameter are not limited according to experimental requirements, preferably the length is not greater than 200 mm and the outer diameter is not greater than 5 mm; the sample cell is preferably made of transparent material; multiple sample cells are arranged to form a sample cell array. The sample cell is preferably axially closed. If nutrient delivery or culture of the sample is required, the sample cell can also be open with openings or slits to allow the sample to interact with the outside world. Furthermore, for cultured samples, the device including the sample cell can be placed in the culture environment, such as an incubator, thermostat, or pressure chamber. The sealing liquid is an oil that is insoluble in water and resistant to temperature, such as silicone oil. Since all the sealing liquids in a sample cell are of the same type, after spectral scanning, the sealing liquid characteristic signal, continuous identical signals of the same length as the sealing liquid, or signals that are the same or basically the same in each sample cell are considered as the sealing liquid. The sealing liquid signal is not processed by subsequent data calculation. Only the sequence of the sealing liquid signal is used as the sample interval and micro-region location for judgment.

[0016] like Figure 7 As shown, the blocking liquid 8 and sample 9 are spaced apart in a single sample cell 4, realizing the micro-region characteristics of blocking liquid-sample-blocking liquid, thus forming N micro-region samples in the sample cell 4. By moving the detection head from one end of the sample cell 4 to the other, the detection of multiple micro-region samples can be achieved, such as... Figure 8 As shown, the arrangement of multiple sample cells 4 can effectively improve detection efficiency.

[0017] In one embodiment, such as Figure 1 As shown, the temperature control module has a temperature sensor and a control unit. The temperature sensor is used to sense the temperature of the sample in the micro-area of ​​the sample cell and feed the temperature back to the control unit in real time. The control unit adjusts the temperature. Furthermore, the temperature of any point in the sample cell can be directly calculated using parameters such as sensor temperature, sample cell and thermally conductive material, and micro-area position. Preferably, a semiconductor TEC semiconductor heating and cooling module is used to maintain the sample micro-area array at different or the same temperature. Preferably, a gradient temperature control method is used for the sample micro-areas to obtain signal differences at various temperatures in different micro-areas. The sample cell temperature is monitored and fed back using a high-sensitivity temperature sensor. Alternatively, a Z-shaped arrangement of heating wires along the sample cell axis can be used to achieve an overall temperature gradient or to set the temperature of one or more micro-areas.

[0018] In one embodiment, such as Figure 1 As shown, the optical path module includes a light source and a detector. The light source is one of LED, laser, or composite spectrum illumination unit, preferably a single or multiple band combination of 200-400nm and 500-900nm. Further, the corresponding band is matched according to the characteristics of the sample to be detected (such as fluorescence band). Dynamic and static light scattering preferably use LED or laser, preferably a single or multiple band combination of 200-900nm. Dynamic and static light scattering preferably share the same illumination source, but separate illumination sources can be provided. Absorption light detection preferably uses composite spectrum (such as pulsed xenon lamp, xenon lamp, halogen lamp, tungsten lamp), preferably a single or multiple band combination of 200-700nm. Fluorescence and dynamic / static light scattering preferably share the same light source, but independent light sources can also be used. like Figure 9 As shown, illumination light sources 10 are provided on both sides of the sample cell 4, and detection light source 11 is moved from one side of the sample cell 4 to the other side to realize detection. The circular sample cell can ensure that no other components occupy the space within a 180-degree or larger angle range, thereby providing sufficient space for the simultaneous layout of different detection optical paths.

[0019] The detector is a single type or a combination of PMT, APD, CMOS, and CCD detectors. Preferably, light scattering techniques are used for photodetection of the sample, such as static light scattering, combined with... Figure 2 As shown, Figure 2 The static light scattering device includes a laser 1, a spatial filter 2, a collimating lens 3, a sample cell 4, a Fourier lens 6, and a photodetector 7. The laser beam from the laser 1 is filtered by the spatial filter 2 and collimated by the collimating lens 3 before entering from one side of the sample cell 4 and exiting from the other side. The outer wall of the sample cell 4 is a transparent glass wall perpendicular to the incident light. When there are no sample particles 5 to be measured in the sample cell 4, the parallel light is emitted from the sample cell 4 and focused by the Fourier lens 6 to the center of the photodetector 7. When there are sample particles 5 in the sample cell 4, the laser light scatters, and a portion of the light diffuses outward at a certain angle to the optical axis. For small dispersed particles, the scattering angle of the scattered light is related to the particle size, and the scattered light will be focused onto the photodetector 7, which is arranged according to the scattering angle. Dynamic light scattering methods, such as Figure 3A typical setup includes, in sequence: a laser 1; a focusing lens 12 to focus the laser beam onto the center of a sample cell 4; the sample cell 4; a classic 90-degree focusing lens for collecting scattered light; and a photomultiplier tube 13, mounted at a fixed angle to receive the scattered light. Assuming the sample in the sample cell is completely homogeneous, the scattered light signal received by the photomultiplier tube 13 will be constant and will not change over time. However, due to impacts from surrounding molecules in the liquid, fine particles constantly undergo random Brownian motion. This Brownian motion causes the signal received by the photomultiplier tube 13 to fluctuate continuously. When the sample particle size is small, the Brownian motion is fast, and the fluctuations in the scattered light signal are correspondingly rapid; conversely, when the particle size is large, the fluctuations are the opposite. This allows for the measurement of particle size by observing the instantaneous changes in the scattered light signal.

[0020] In one embodiment, such as Figure 1 As shown, the sample loading method of the injection module is as follows: The injection module can inject any sample from the sample reservoir into the sample cell. Through cross-injection and the injection control module, the composition of a single sample cell can be changed (e.g., mixing of two or more samples). Furthermore, by cross-injecting the sample with a sealing liquid (e.g., oil), the samples in the sample cell are separated, allowing for the formation of various micro-region samples within a single sample cell. Furthermore, one or both ends of the sample cell are sealed to limit changes in the composition or volume of the micro-region sample caused by changes in the external environment (e.g., pressure, temperature, electric field). Furthermore, to prevent overlap between the sealing liquid and the sample signal, the specific signal of the sealing liquid is separated by using its spectral characteristics and / or by adding characteristic signal components to the sealing liquid, while also avoiding the influence of sealing liquid residue on the micro-region sample. In one embodiment, such as Figure 1 As shown, the sample storage cell has multiple cells forming a sample storage cell array, which is preferably a centrifuge tube or a multi-well plate, and may further be other shapes of liquid storage cells. The sample storage cells are movable relative to the injection module so that multiple or single sample storage cells can be injected. In one embodiment, such as Figure 1 As shown, the module also includes a liquid collection tank for collecting waste liquid and cleaning fluid; and for centralized collection of waste liquid; In one embodiment, such as Figure 1As shown, the spectral detection and analysis unit preferably uses axial scanning detection relative to the sample cell. Based on the micro-region characteristics of the blocking liquid-sample-blocking liquid, one or more types of signals, including light scattering, fluorescence, and absorption, exhibit a phenomenon of no-weak-strong-weak-no (or no signal-signal-no signal-signal...) changes. Therefore, the changes in sample performance with environmental conditions or different treatments, including interaction strength, can be obtained based on changes in signal strength (or presence / absence). Furthermore, changes in the peak value of the signal can also indicate changes in the sample performance with the environment or different treatments. Further, the corresponding sample signal can be obtained through the correspondence between the moving distance and the micro-region. After further signal analysis, the changes in fluorescence and / or absorption with the sample environment or different treatments reflect changes in sample properties, such as the absorption reflecting the spatial structure, integrity, and purity of nucleic acids or proteins; and the fluorescence reflecting the spatial structure and interaction of fluorescent molecules or labeled molecules.

[0021] Most biomolecules possess characteristic absorption spectra, fluorescence spectra (such as those with intrinsic spontaneous fluorescence characteristics or exogenous fluorescent labels), and light scattering (including dynamic and static light scattering). This product is based on light scattering technology (including dynamic light scattering and static light scattering) and micro-area array continuous spatiotemporal temperature control technology. Light scattering is an effective technique for detecting particle size, dispersion, and other properties of molecules from submicron to nanometer scale.

[0022] Microfluidics technology is a rapidly maturing technology that has been successfully commercialized in various sub-fields, such as digital PCR instruments, protein chips, nucleic acid chips, and cell sorting. Currently, drug screening primarily utilizes compound or small molecule library screening, molecular simulation, fluorescence detection, flow cytometry, molecular interaction techniques, and other molecular analysis methods. While these methods are diverse, their inherent characteristics limit their application due to constraints such as throughput, cost, sensitivity, and unsuitability for large sample volumes. Furthermore, their widespread use is influenced by the size, conformational sensitivity, and solution environment of different drug molecules. Using conventional capillaries, axially open capillaries, or other shaped sample cells (e.g., capillaries with one-third removed) is preferable as the preferred sample cell method, allowing for control over sample size, cost, and throughput.

[0023] Fluorescence is the light emitted by an object after it has absorbed short-wavelength illumination and stored energy, which is then emitted as longer-wavelength light. During the absorption of incident light, photon energy is transferred to the molecules, exciting them. Electrons transition from lower to higher energy levels, forming excited-state molecules. Excited-state molecules are unstable and can return to their ground state through radiative transitions (fluorescence, phosphorescence) and non-radiative transitions (vibrational relaxation, internal conversion, external conversion, intersystem crossing). Fluorescence is the photon radiation produced when a molecule transitions from the lowest vibrational energy level of its first excited singlet state to any vibrational energy level of its ground state. Fluorescence radiation energy is lower than the excitation energy, and the fluorescence wavelength is longer than the excitation wavelength (see diagram). Figure 4 When a substance is irradiated and absorbs light, electrons within the molecules transition from the ground state S0 to a higher energy level S2, becoming excited. Molecules in the excited state are unstable; they first transfer some energy to surrounding molecules through internal energy conversion, returning to the lowest electronically excited vibrational energy level S1 (called the first-order electronically excited vibrational energy level). Molecules in this energy level release the remaining energy by emitting corresponding photons, returning to the ground state S0 vibrational energy level, thus producing fluorescence. Because some energy is consumed before fluorescence emission, fluorescence follows the principle that the emission wavelength is greater than the excitation wavelength: λ2' > λ2 > λ1 (Stockes shift); λ1: absorption wavelength 1; λ2: absorption wavelength 2 (internal energy conversion); λ2': emission wavelength (fluorescence).

[0024] Dynamic and / or static light scattering, when used for sample detection, obeys wavelength characteristics. The most common static light scattering—Mie scattering—and dynamic light scattering—Rayleigh scattering are both wavelength-dependent. In the former, the scattering intensity is inversely proportional to the square of the wavelength, while in the latter, it is inversely proportional to the fourth power of the wavelength. In both cases, the shorter the wavelength, the stronger the scattering. The development of optoelectronics and computing technology has made light scattering a routine method in molecular research. Laser light scattering includes two main parts: static and dynamic scattering. In static light scattering, by measuring the angle and concentration dependence of the average scattered light intensity, the weight-average molecular weight Mw, root-mean-square cyclotron radius Rg, and second virial coefficient A2 of the polymer can be obtained. In dynamic light scattering, a digital correlator is used to record the fluctuations in scattered light intensity over time, obtaining the time correlation function, the characteristic relaxation time τ, and subsequently the translational diffusion coefficient PDi and the hydrodynamic radius R.

[0025] In practical applications, Mie scattering and static Rayleigh scattering are classic theoretical applications of static light scattering. For particles suspended in a liquid, Mie scattering establishes a functional relationship between light intensity and angle, thus providing information on particle size and shape. For polymer solutions, the dependence of light intensity on angle and concentration (i.e., concentration dependence and angle dependence) can be used with Zimm plots (or other similar methods) to obtain absolute weight-average molecular weight, second virial coefficient, root-mean-square radius of gyration, and other parameters. Dynamic Light Scattering (DLS) is based on elastic light scattering, Brownian motion, and dynamic Rayleigh scattering. Also known as Photon Correlation Spectroscopy (PCS) or quasi-elastic scattering, DLS measures the fluctuation of light intensity over time. DLS technology for measuring particle size has advantages such as accuracy, speed, and good repeatability, and has become a routine characterization method in drug, biomolecule, and nanomaterial research. The Brownian motion of particles causes fluctuations in light intensity. The speed of this motion depends on the particle size and the viscosity of the medium; smaller particles and lower medium viscosity result in faster motion. When light passes through a solution, particles scatter the light. Detecting the light signal at a set angle yields the result of the superposition of multiple scattered photons. The instantaneous light intensity is not a fixed value but fluctuates around a certain average value. However, the amplitude of this fluctuation is related to the particle size. (See...) Figure 2 , Figure 3 , Figure 5 , Figure 6 .

[0026] The static light scattering theory formula is as follows: Where: K: optical constant, K=4π 2 (dn / dc) 2 n0 2 / (N A λ0 4 R: Rayleigh factor, R=Ir 2 / I0; Weight-average molecular weight; R g : Root mean square radius of gyration; A2: Second virial coefficient; n: Refractive index of the solvent; C: Concentration of solute molecules (g / mol); n0: Refractive index of the standard liquid; dn / dc: Ratio of the refractive index of the solution to its concentration change; N A λ: Avogadro's constant; λ0: wavelength of incident light; I: intensity of incident light; I0: intensity of scattered light; r: distance from the light source to the measurement point.

[0027] This product preferentially uses highly sensitive fluorescence and light scattering signals for the analysis of molecular interactions, structural composition and changes; based on changes in particle size or molecular weight or the peak migration rate of the sample with temperature gradient, molecular change characteristics or molecular interaction characteristics can be calculated or inverted.

[0028] The above description is merely a specific embodiment of this disclosure, but the scope of protection of this disclosure is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this disclosure should be included within the scope of protection of this disclosure. Therefore, the scope of protection of this disclosure should be determined by the scope of the claims.

Claims

1. A microarray spectral scanning analysis system based on a spatiotemporally continuous temperature gradient, characterized in that, The system includes a sample storage tank, a sample cell, an injection module, a temperature control module, an optical path module, a motion device, and a spectral detection and analysis unit. The sample storage tank corresponds to the inlet of the injection module and is used for sample preparation. The sample cell corresponds to the outlet of the injection module and serves as a sample carrier accessory for detection. The injection module establishes the injection relationship between the sample cell and the sample storage tank by closing or opening one or more channels. The temperature control module uses real-time or time-sharing detection during temperature increase to establish a continuous temperature gradient for the micro-region sample in the sample cell. The optical path module detects the optical signal of the micro-region sample in the sample cell using single or combined methods of fluorescence, dynamic and static light scattering, and absorption light detection. The motion device is used for the corresponding interaction between the sample storage tank and the sample cell. The spectral detection and analysis unit is used for axial scanning detection relative to the sample cell, and analyzes the changes of the sample under different environmental conditions or treatments based on the micro-region characteristics of the sealing liquid-sample-sealing liquid.

2. The microarray spectral scanning analysis system based on a spatiotemporal continuous temperature gradient according to claim 1, characterized in that, The sample introduction module can introduce samples manually or semi-automatically via injection or negative pressure. It can also arrange samples and isolation liquid by simultaneously injecting them point by point or multiple points into axially non-closed sample cells through pipetting or injection. The sample cells with multiple micro-area arrays can be loaded into the instrument for detection manually or automatically.

3. The microarray spectral scanning analysis system based on a spatiotemporal continuous temperature gradient according to claim 1, characterized in that, The sample cell is circular or square in shape; the inner length of the sample cell is preferably no more than 200 mm; the sample cells are arranged in a straight line, a ring or other shapes.

4. The microarray spectral scanning analysis system based on a spatiotemporal continuous temperature gradient according to claim 1, characterized in that, The optical path module includes a light source and a detector. The light source is one of LED, laser, or composite spectrum illumination unit, and the wavelength is 200-400nm or 500-900nm, or a single or multiple wavelength band combination. The detector is a single or combined type of detector such as PMT, APD, CMOS, and CCD.

5. The microarray spectral scanning analysis system based on a spatiotemporal continuous temperature gradient according to claim 4, characterized in that, Dynamic and static light scattering are achieved using lasers; the fluorescent illumination unit is either an LED or a laser; and the absorption light detection preferably uses a composite spectral illumination unit.

6. The microarray spectral scanning analysis system based on a spatiotemporal continuous temperature gradient according to claim 1, characterized in that, The spectral detection and analysis unit can also obtain the spectral information of the sample as it is subjected to different environments or treatments based on the change in the peak value of the signal.

7. The microarray spectral scanning analysis system based on a spatiotemporal continuous temperature gradient according to claim 6, characterized in that, The spectral detection and analysis unit also reflects changes in the properties of the sample by detecting changes in fluorescence and / or absorption light as the sample environment or different treatments change.

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