MXPA00009167A - Method and device for analysing the three-dimensional distribution of a component in a sample - Google Patents

Abstract

A device for and a method of analysing a sample, comprising:a sample positioning unit (1) for positioning a sample (3);a radiation generating unit (16) for providing at least one beam of electromagnetic radiation to each of first and second surfaces of the sample (3);an imaging unit (23) for providing at least one image from radiation transmitted through each of the first and second surfaces (3a, 3b) of the sample (3);a detector unit (25) for capturing the images provided by the imaging unit (23) and generating signals corresponding thereto;and an analysing unit (61) for operating on the signals received from the detector unit (25) and generating signals representative of the three-dimensional distribution of at least one component in the sample (3).

Description

METHOD AND DEVICE FOR ANALYZING THE THREE-DIMENSIONAL DISTRIBUTION OF A COMPONENT IN A SAMPLE The present invention concerns a device for and a method of analyzing a sample, in particular a tablet, a capsule or a bulk powder.

EP-A-0767369 describes a device for analyzing a sample by measuring the transmission using infra-red radiations nearby. This device, however, is capable of providing only limited information regarding the content of a sample, typically the amount of a particular component in a sample, and can not provide detailed information, for example, regarding the three-dimensional distribution. of one or more components in a sample.

It is a purpose of the present invention to provide a device for and a method of analyzing a sample, in particular a tablet, capsule or bulk powder and especially a tablet or capsule of the multiple unit tableting system, which is capable of providing information as for the three-dimensional distribution of one or more components in the sample.

REF.122934 Indeed the present invention provides a device for analyzing a sample, comprising: a unit for placing samples to place a sample; a radiation generating unit for providing at least one beam of electromagnetic radiation for each of the first and second surfaces of the sample; an imaging unit for providing at least one image from the radiation transmitted through each of the first and second surfaces of the sample; a sensor unit for capturing the images provided by the imaging unit and generating the signals corresponding thereto; and an analysis unit for working on the signals received from the detector unit and generating signals representative of the three-dimensional distribution of at least one component in the sample.

Preferably, the sample placement unit comprises a slide guide through which the displays that are in use pass.

In one embodiment, the sample placement unit is configured in such a way that ours are moved in a slow way through the sliding guide.

In another embodiment, the sample placement unit is configured in such a way that the samples are moved continuously through the sliding guide.

In one embodiment at least one of the radiation beams is collimated.

In another embodiment, at least one of the radiation beams is convergent.

In another embodiment, at least one of the radiation beams is divergent.

In one embodiment the principal axis of at least one of the radiation beams is substantially normal to the respective surface of the sample.

In another embodiment, the main axis of at least one of the radiation beams is at an angle to the respective surface of the sample.

In one embodiment at least one of the radiation beams is dimensioned to radiate substantially all of the respective surface of the sample.

In another embodiment, at least one of the radiation beams is dimensioned to irradiate an area smaller than that of the respective surface of the sample.

In a preferred embodiment the radiation generating unit is configured to move, with at least one of the radiation beams in use in at least one direction being in use and thus to sweep at least one of the radiation beams on substantially all of the respective surface of the sample.

Preferably the first and second surface of the sample are opposite oriented surfaces.

Preferably, at least one of the radiation beams is visible light.

Preferably, at least one of the radiation beams is infra-red radiation.

More preferably, the infra-red radiation is in the near infra-red region.

Even more preferably, infra-red radiation has a frequency in the range corresponding to wavelengths from 700 to 1700 nm, particularly from 700 to 1300 nm.

Preferably, at least one of the radiation beams is X-ray radiation.

Preferably, the radiation generating unit comprises at least one radiation source and at least one optical element.

Preferably, the radiation generating unit further comprises a mobile diffuser in the output line of each radiation source.

Preferably, the radiation generating unit comprises a polarizer in the output line of each radiation source.

In a preferred embodiment, the radiation generating unit comprises the first and second associated radiation sources and optical elements, each of the radiation sources providing at least one radiation beam for respectively irradiating the first and second surfaces of the sample.

In any one or each of them, the radiation sources comprise a laser, preferably a diode laser.

In any other modality or in each of them, the radiation sources comprise a light emitting diode.

Preferably, the imaging unit comprises at least one optical element for providing at least one radiation image transmitted through each of the first and second surfaces of the sample.

More preferably, the imaging unit comprises at least one polarizer for polarizing the radiation transmitted through each of the first and second surface of the sample.

More preferably, the imaging unit additionally comprises at least one beam splitting device for providing a plurality of images of different frequency or single frequency band, of radiation transmitted through each of the first and second surface of the sample.

In one embodiment, the beam splitting device comprises a frequency-dependent beam splitting device, which together with at least one optical element provides a plurality of images of different frequency or band of single frequencies of radiation transmitted through each of the first and second surfaces of the sample.

In another embodiment, the beam splitting device comprises a non-frequency dependent beam splitting device, which separates the radiation transmitted through each of the first and second surfaces of the sample into a plurality of components, and a plurality of filters for filtering each of the respective components to provide radiation of different frequency or band of unique frequencies, the beam splitting device and the filters together with at least one optical element that provides a plurality of images of different frequency or band of frequencies unique to the radiation transmitted through each of the first and second surfaces of the sample.

In a further embodiment the beam splitting device comprises a transmission network, which together with at least one optical element provides a plurality of images of different frequency or single frequency band of the radiation transmitted through each of the first and second surfaces of the sample.

In yet another embodiment, the beam splitting device comprises a prismatic array, which separates the radiation transmitted through each of the first and second surface of the sample in a plurality of components, and a plurality of filters to filter each of them. the respective components, to provide radiation of different frequency or single frequency band, the prismatic reticulate and the filters together with at least one optical element that provide a plurality of images of different frequency or single frequency band of the radiation transmitted through each of the first and second surfaces of the sample.

In still a further embodiment, the beam splitting device comprises a plurality of lenses, which separate the radiation transmitted through each of the first and second surfaces of the sample in a plurality of components., and a plurality of filters for filtering each of the respective components to provide radiation of different frequency or single frequency band, the lenses and filters together with at least one optical element that provide a plurality of images of different frequency or band of single frequencies of radiation transmitted through each of the first and second surfaces of the sample.

Preferably, the detector unit comprises at least one detector.

In one embodiment, the detector unit comprises a single detector.

In another embodiment, the detector unit comprises a plurality of detectors.

In a preferred embodiment, the at least one detector is a two-dimensional network detector.

In another preferred embodiment each detector is a sub-network of a network detector.

In a preferred embodiment, the at least one detector is a one-dimensional network detector.

In one embodiment the detector unit is configured in such a way that, in use the or at least one detector is moved to capture the images provided by the imaging unit.

Preferably, at least one detector comprises one of a CMOS microelement, a CCD microelement or a focal plane network.

The present invention also provides a method of analyzing a sample, comprising the steps of: providing a sample; irradiating the first and second surface of the sample each with at least one beam of electromagnetic radiation; forming images with the radiation transmitted through each of the first and second surfaces of the sample; capture the image formed with the radiation and generate signals that correspond to it; and working on the signals corresponding to the image formed with the radiation and generating signals representative of the three-dimensional distribution of at least one component in the sample.

In one embodiment, the sample is stationary during irradiation.

In another embodiment, the sample is in motion during irradiation.

In one embodiment at least one of the radiation beams is collimated.

In another embodiment, at least one of the radiation beams is convergent.

In a further embodiment at least one of the radiation beams is divergent.

In one embodiment the principal axis of at least one of the radiation beams is substantially normal to the respective surface of the sample.

In another embodiment the main axis of at least one of the radiation beams is at an angle to the surface of the sample.

In one embodiment at least one of the radiation beams is dimensioned to radiate substantially the respective surface of the sample.

In another embodiment, at least one of the radiation beams is dimensioned to irradiate an area smaller than that of the respective surface of the sample and the respective surface of the sample is irradiated substantially entirely by the scanning of at least one of the beams of radiation on it.

In a further embodiment at least one of the radiation beams is dimensioned to irradiate an area smaller than that of the respective surface of the sample and the respective surface of the sample is irradiated substantially completely by the movement of the sample to be swept by at least one of the radiation beams on the a.

Preferably, at least one of the radiation beams is in the form of a line.

Preferably the first and second surfaces of the sample are opposite oriented surfaces - Preferably, the radiation comprises a single frequency, a single frequency band, a plurality of single frequencies or a plurality of frequency bands.

In one embodiment at least one of the radiation rays is continuous.

In another embodiment at least one of the radiation beams is pulsed.

Preferably, the frequency or frequency band of the radiation in each pulse is different.

Preferably, at least one of the radiation beams is visible light.

Preferably, at least one of the radiation beams is infra-red radiation.

More preferably, the infra-red radiation is in the near infra-red region.

Even more preferably, infra-red radiation has a frequency in the range corresponding to wavelengths from 700 to 1700 nm, particularly from 700 to 1300 nm.

Preferably, at least one of the radiation beams is X-ray radiation.

Preferably, the step of forming images with the radiation comprises the step of providing a plurality of images of different frequency or band of single frequencies from radiation transmitted through each of the first and second surfaces of the sample.

A preferred embodiment of the present invention will now be described below by way of example with reference to the appended drawings, in which: Figure 1 schematically illustrates the elements of an analysis device according to a preferred embodiment of the present invention.

Figure 2 schematically illustrates the unit for placing the sample of the device of Figure 1; Figure 3 schematically illustrates the radiation generating unit of the device of Figure 1; Fig. 4 schematically illustrates the imaging unit and the detector unit of the device of Fig. 1; Fig. 5 illustrates schematically an alternative imaging unit for the device of Fig. 1; Fig. 6 illustrates schematically a first form of beam splitting device for the image forming unit of Fig. 5; Fig. 7 schematically illustrates a second form of beam splitting device for the image forming unit of Fig. 5; Fig. 8 schematically illustrates a third form of the beam splitting device for the image forming unit of Fig. 5; Fig. 9 schematically illustrates a fourth form of the beam splitting device for the imaging unit of Fig. 5; Fig. 10 illustrates schematically a fifth form of beam splitting device for the image forming unit of Fig. 5; Figure 11 illustrates an image generated by the analysis unit from the radiation transmitted through the first surface of a first sample; Figure 12 illustrates an image generated by the analysis unit from the radiation transmitted through the second surface of the first sample; Figure 13 illustrates an image generated by the analysis unit, from the radiation transmitted through the first surface of a second sample; Figure 14 illustrates an image generated by the analysis unit, from the radiation transmitted through the second surface of the second sample; Figure 15 illustrates an intensity histogram as a function of the shadow of gray corresponding to the image of Figure 13; Figure 16 illustrates an intensity histogram as a function of the shadow of gray corresponding to the image of Figure 14; Fig. 17 illustrates schematically an alternative of detector unit for the device of Fig. 1; Fig. 18 illustrates schematically an alternative of radiation generating unit for the device of Fig. 1; Figure 19 schematically illustrates another alternative of radiation generating unit for the device of Figure 1; Fig. 20 schematically illustrates a further alternative of radiation generating unit, an alternative of imaging unit and an alternative of detector unit for the device of Fig. 1; Y Figure 21 schematically illustrates a still further alternative of radiation generating unit for the device of Figure 1.

The device comprises a unit for placing the sample 1 for directing a sample 3, in this mode a tablet or capsule, for positioning it and substantially presenting the first 3a and second 3b, surfaces of the same oriented opposite. The sample positioning unit 1 comprises a base 5 and a sliding guide 7, in this mode a tubular section formed of a transparent material for electromagnetic radiation, through which the samples 3 are passed., either continuously in which case the respective sample 3 is in motion during the analysis, or in a leisurely manner, in which case each respective sample 3 is per stationary turn during the analysis. The sample placement unit 1 additionally comprises the first and second protective plates 12 and 13 which are disposed respectively adjacent to the first and second surfaces 3a, 3b of the sample 3. Each of the protective plates 12, 13 includes a opening 14, 15 that define a window through which radiation can pass. In practice, the openings 14, 15 in the protective plates 12, 13 are dimensioned to be of slightly smaller dimension than the first and second surfaces 3a, 3b of the sample 3. In this way, all radiation passing to a unit of Imaging 23 must pass through the openings 14, 15 in the protective plates 12, 13 and consequently the mass of the sample 3, with the protective plates 12, 13, which thus act as a blocking for any radiation external of the openings 14, 15 in them.

The device further comprises a radiation generating unit 16 for the generation of electromagnetic radiation with which to irradiate the sample 3. In this embodiment the radiation generating unit 16 is configured to provide radiation having a pre-determined frequency band. In a particularly preferred embodiment, the radiation generating unit 16 is configured to provide radiation having a narrow frequency band, preferably in the near infrared region. In alternative embodiments, the radiation generating unit 16 may be configured to provide radiation comprising a single frequency, a plurality of single frequencies or a plurality of frequency bands, each preferably narrowband. In addition, the radiation can be either continuous or impulse.

The radiation generating unit 16 comprises at least one radiation source 17 and a plurality of optical elements 18, 19, 20, 21a, 21b, 21c, 22a, 22b, 23a, 23b, 23c, 23d, including a polarizer 18, a diffuser 19, a beam splitting device 20, first to third mirrors 21a, 21b, 21c, first and second lenses 22a, 22b and first to fourth protective plates 23a, 23b, 23c, 23d, which allow measurements of the Transmission are taken in both directions through the sample 3, that is, from the first surface 3a to the second surface 3b and vice versa, and reflectance measurements are made from both surfaces of the sample 3, that is, from the first and second surfaces 3a, 3b. In this embodiment the polarizer 18 is included in the output line of at least one radiation source 17 to provide fully polarized radiation. In this embodiment, the diffuser 19, typically a rotary or vibratory element, is disposed at the outlet line of at least one radiation source 17 to prevent staining that may occur when at least one radiation source 17 is, for example, a To be. In a particularly preferred embodiment, the radiation generating unit 16 additionally comprises a fiber bundle (not illustrated) by which radiation is provided to the imaging unit 23. In particularly preferred embodiments at least one radiation source 17 may comprise any of a visible light source, such as an arc lamp, an X-ray source, a laser, such as a diode laser, or a light emitting diode (LED). In a particularly preferred embodiment, the radiation generating unit 16 comprises a plurality of radiation sources 17, typically a superposition of light emitting diodes or diode lasers, with which the sample 3 can be selectively irradiated. In this embodiment, the radiation generating unit 16 is configured to provide collimated radiation beams which respectively are oriented at an angle with and uniformly radiating, substantially the entire area of the first and second surfaces of the sample, 3. This configuration advantageously causes, at higher incident angles, that in the absence of the sample 3, the radiation will not pass to the imaging unit 23 and subsequently to a detector unit 25, which could cause damage to them. In a particularly preferred embodiment the additional device comprises non-reflective elements (not shown) towards which the radiation is directed when the sample 3 is not present. In an alternative embodiment the radiation generating unit 16 may be configured to provide collimated radiation beams which are oriented substantially orthogonally towards the first and second surfaces 3a, 3b of the sample 3. In a further alternative embodiment the radiation generating unit 16 it may be configured to provide convergent radiation beams whose point of convergence is located beyond the first and second surfaces 3a, 3b of the sample 3 to which the radiation is provided. In yet a further alternative embodiment, the radiation generating unit 16 may be configured to provide beams of divergent radiation.

As will be described later, at least one radiation source 17, the beam splitting device 20, the mirrors 21a, 21b, 21c and the shield plates 23a, 23b, 23c, 23d are functionally configured so that the detector unit 25 captures the respective transmission and reflectance images. In a first configuration, at least one radiation source 17 provides radiation to only the first surface 3a of the sample 3 via the beam splitting device 20 and the first mirror 21a, with radiation that is prevented from passing to the second surface 3b of the sample 3 by the second protective plate 23b and the radiation reflected from the first surface 3a of the sample 3 which is blocked by the third protective plate 23c. In this way, the detector unit 25 is provided with a radiation image transmitted through the sample 3 in the direction from the first surface 3a to the second surface 3b. In a second configuration, at least one radiation source 17 provides radiation to only the first surface 3a of the sample 3 via the beam splitting device 20 and the first mirror 21a, with radiation whose passage is prevented to the second surface 3b of the shows 3 by the second protective plate 23b and the radiation transmitted through the sample 3 in the direction from the first surface 3a to the second surface 3b which is blocked by the fourth protective plate 23d. In this way, the detector unit 25 is provided via the second and third mirrors 21b, 21c of a radiation image reflected from the first surface 3a of the sample 3. In a third configuration, at least one radiation source 17 provides radiation via the beam splitting device 20 to only the second surface 3b of the sample 3, with radiation whose passage is prevented to the first surface 3a of the sample 3 by the first protection plate 23a and the radiation reflected from the second surface 3b of the shows 3 which is blocked by the fourth shield plate 23d. In this way, the detector unit 25 is provided via the second and third mirrors 21b, 21c of a radiation image transmitted through the sample 3 in the direction of the second surface 3b towards the first surface 3a. In a fourth configuration, at least one radiation source 17 provides radiation via the beam splitting device 20 to only the second surface 3b of the sample 3, with radiation whose passage is prevented to the first surface 3a of the sample 3 by the first protective plate 23a and the radiation transmitted through the sample 3 in the direction of the second surface 3b towards the first surface 3a which is blocked by the third protective plate 23c. In this way, the detector unit 25 is provided with a radiation image reflected from the second surface 3b of the sample 3. In use, the radiation is selectively provided, preferably either simultaneously or alternatively, to the first and second surfaces 3a , 3b of the sample 3 so that the detector unit 25 captures the respective transmission and reflectance images.

The additional device comprises an imaging unit 23 and a detector unit 25, the imaging unit 23 provides a radiation image received from the sample 3 towards the detector unit 25. As illustrated in figure 4, the unit image formation 23 comprises a polarizer 26 to completely polarize the received radiation and at least one optical element 27, in this mode at least one lens, and the detector unit 25 comprises at least one detector 29 to capture the image formed with the radiation . In this embodiment, at least one detector 29 comprises a bi-dimensional network detector, particularly a CMOS microelement, a CCD microelement or a network in the focal plane. In a particularly preferred embodiment, at least one detector 29 comprises an InGaAs camera. In a particularly preferred embodiment the image forming unit 23 additionally comprises a fiber bundle (not shown) whereby the image formed with the radiation is provided to at least one detector 29. In a most preferred embodiment each discrete fiber or a group of fibers in the beam is coupled to an independent detector '29.

In a particularly preferred embodiment, in order to provide additional information for the three-dimensional distribution of one or more components in the sample 3, the device is configured to analyze the sample 3 using radiation of a plurality of different frequency or band of unique frequencies, each a preferably narrow band.

In one embodiment, the radiation generating unit 16 can be selectively configured to provide radiation of different frequency or band of unique frequencies with which the sample 3 is irradiated. In practice, this can be achieved by configuring the radiation generating unit 16 to provide radiation pulses, each of which at a different frequency or single frequency band, and to activate the detector unit 25 with each pulse. In irradiation, the sample 3 with the radiation of each respective single frequency or frequency band, the detector unit 25, receives a plurality of independent images which are then worked by the one analysis unit 61 as will be described later.

In another embodiment, as illustrated in Figure 5, the image forming unit 23 may additionally comprise a beam splitting device 31 for providing two or more images of different frequency or frequency band unique to the detector unit 25. Wherever two or more images are provided to the detector unit 25, the detector unit 25 comprises either a corresponding number of detectors 29 or a single detector 29 in which each image is provided on its turn. In a mode where a plurality of detectors is employed, the sensors 29 may be provided with a single microelement having a plurality of sub-networks each of which defines a detector 29. The beam splitting device 31 may take many shapes. In one form, as illustrated in Figure 6, the beam splitting device 31, comprises a frequency-dependent beam splitting device 33, which separates the image I, received from at least one lens 27 in a first image Ii of a first frequency or frequency band and a second I2 image of a second frequency or frequency band. In another form, as illustrated in Figure 7, the beam splitting device 31 comprises a non-frequency dependent beam splitting device 35 that separates the received image I from at least one lens 27 into two equivalent components, a first filter 37 for filtering one of the components to provide a first image Ii of a first frequency or frequency band and a second filter 39 for filtering the other component to provide a second image I2 of a second frequency or frequency band. In a further form, as illustrated in FIG. 8, the beam splitting device 31 comprises a transmission lattice 41, which separates the received image I from at least one lens 27 in a first image Ii of a first frequency or frequency band. frequencies and a second I2 image of a second frequency or frequency band. In yet another form, as illustrated in FIG. 9, the beam splitting device 31 comprises a prismatic array 43, which separates the received image I from at least one lens 27 into two equivalent components, a first filter 45 for filtering one of the components for providing a first image Ii of a first frequency or frequency band and a second filter 47 for filtering the other component to provide a second image I2 of a second frequency or frequency band. In still yet another additional form, as illustrated in FIG. 10, the beam splitting device 31 comprises the first, second and third lenses 49, 51, 53 which respectively separate the received image I from at least one lens 27 in FIG. first, second and third equivalent components, a first filter 55, for filtering the first component to provide a first image Ii of a first frequency or frequency band, a second filter 57 for filtering the second component to provide a second image 12 of a second frequency or frequency band and a third filter 59 for filtering the third component to provide a third image I3 of a third frequency or frequency band.

The device further comprises an analysis unit 61 comprising processing means (not shown) for working on the signals received from one or more detectors 29 to extract relevant information as signals. The extracted signals may be provided on a screen (not shown) to expose one or more two-dimensional images which are in part representative of the three-dimensional distribution of one or more components in a sample 3, such as an active ingredient. or an excipient in a pharmaceutical sample. By way of example, FIGS. 11 and 12 respectively illustrate images generated from radiation transmitted through the first and second opposite facing surfaces 3a, 3b, of a first sample 3 including a component evenly distributed in a conveyor matrix and FIGS. and 14 respectively illustrate images generated from radiation transmitted through the first and second surfaces 3a, 3b oppositely oriented from a second sample 3 which includes a component distributed non-uniformly in a carrier matrix (with the component being confined to a thickness adjacent to the first surface 3a of the sample 3). In these images, the brighter or more intense regions are representative of the component. As will be obvious to the naked eye, the image in Figure 14, which is of radiation transmitted through the second surface 3b of the second sample 3, includes regions of non-discrete light and is representative that no component is present adjacent to the second surface 3b of the sample 3. Indeed, figures 13 and 14 clearly show that to determine the three-dimensional distribution of a component in a sample it is not sufficient to form the image from the radiation transmitted in a single direction through a sample. The extracted signals are then converted into the respective gray scale vectors that are mathematically representative of the extracted and provided signals for the generation of, for example, histograms which are representative of the intensity as a function of the gray scale. In the images of figures 11 to 14, each image is an 8-bit image, but of course to improve the resolution of each image it could, for example, be a 24-bit image. By way of example, figures 15 and 16 represent respectively histograms corresponding to the transmission images from the second sample 3 as illustrated in figures 13 and 14. As a measure of the homogeneity of a sample 3, analysis techniques of Monovariable or multivariable images can be applied to the histograms; principal component analysis, partial least square analysis or neural set analysis that are common multivariate image analysis techniques. Such a measurement, when calibrated, can be correlated to the three-dimensional distribution of a component in a sample 3. These converted signals can then be provided to the sample manufacturing equipment 3 for process control, such as control of mixing systems and the selection of the sample. In this preferred embodiment, independent histograms are generated from unique images generated from radiation transmitted through the respective surfaces 3a, 3b of a sample 3. In an alternative embodiment the images generated from each transmission measurement could be interleaved and work with them as a single histogram. In another alternative mode the histograms could be generated from a plurality of images generated from each transmission measurement, then they could be worked with said histograms independently or interleaved before working with them.

In a first mode of use, when the samples 3 are in continuous movement through the slide guide 7 of the sample placement unit 1, the radiation generating unit 16 is activated so as to irradiate each respective sample 3 when it is at a predetermined position in front of it with radiation of a single frequency or band of frequencies or with radiation comprising a plurality of frequencies or bands of unique frequencies. In a particularly preferred embodiment, the radiation generating unit 16 is activated by the reception of a signal from a sensor (not shown) which confirms the predetermined position of the respective sample 3. At the same time, the detector unit 25 detects the radiation images received from the sample 3 and the analysis unit 61 extracts as signals the relevant information which is representative of the three-dimensional distribution of one or more components in the sample 3, said The extracted signals are then converted and used additionally.

In a second mode of use, when the samples 3 are moved slowly through the slide guide 7 of the sample placement unit 1, the radiation generating unit 16 is activated so as to irradiate each respective sample 3 when is stationary in a pre-determined position in front of it with radiation of a single frequency or band of frequencies or with radiation comprising a plurality of frequencies or single frequency bands. Otherwise, the device operates as in the first embodiment described above.

In the preferred embodiment described above, the radiation generating unit 16 is configured to radiate substantially the entire area of each of the first and second surfaces 3a, 3b of the sample 3 and at least one detector 29 in the detector unit 25, which is a detector with two-dimensional network, captures the image of the complete sample at the same moment. It will be appreciated, however, that other configurations are possible.

In one modification, as illustrated in Figure 17, the device comprises the same radiation generating unit 16 as in the preferred embodiment described above, but instead of being a two-dimensional network detector at least one detector is a detector 29 with mono-dimensional network, particularly a CMOS microelement, a CCD microelement or a focal plane network, which is of sufficient length to capture the image of the sample in one direction and is moved in the orthogonal direction to capture the sample image complete in a given base time. In this embodiment, the detector unit 25 includes a plate 63 which includes a narrow slot 65, which extends in one direction, through which the radiation in use passes and behind which at least one detector 29 is placed, with less a detector 29 and the plate 63 that are moved together in unison in the orthogonal direction to capture the image of the entire sample at a given base time.

In another modification as illustrated in FIG. 18, the device comprises the same detector unit 25 as in the preferred embodiment described above, but instead of the radiation generating unit 16 which is uniformly configured to radiate substantially the first and second one. surfaces 3a, 3b of the sample 3, the radiation generating unit 16 is configured to generate a radiation line in a direction which is in use in scanning in the orthogonal direction on the respective surfaces 3a, 3b of the sample 3. In this embodiment the radiation generating unit 16 includes on the input line of the beam splitting device 20 a plate 67 including a narrow slot 69 extending in a direction through which the radiation in use is provided, when the plate 67 is in use moved in the orthogonal direction, so as to substantially sweep the entire area of the surfaces. respective bands 3a, 3b of sample 3, with the radiation line. In this embodiment, at least one detector 29 in the detector unit 25 may comprise either single or two-dimensional network detectors. When at least one detector 29 is a detector with a one-dimensional network, the detector unit 25 has the same configuration as the first modification described above and the plate 63 in the detector unit 25 is in use moved in the orthogonal direction in unison together with the plate 67 in the radiation generating unit 16 to capture the image of the complete sample at a given time base.

In a further modification, as illustrated in Figure 19, the device comprises the same detector unit 25 as in the preferred embodiment described above, but instead of the radiation generating unit 16 which is configured to radiate substantially uniformly and completely the first and second surfaces 3a, 3b of sample 3, the radiation generating unit 16 is configured to generate a radiation line in one direction. In this embodiment, the slide guide 7 of the sample placement unit 1 is configured so that each sample 3 moves therethrough in relation to the radiation line. In this way, the entire area of the respective surfaces 3a, 3b of the sample 3 is substantially swept with the radiation line. In this embodiment the radiation generating unit 16 includes a plate 71 disposed in the input line of the beam splitting device 20 which includes a narrow slot 73 extending in a direction through which the radiation in use is provided. In this way, the image of the complete sample is captured at a determined base time when the sample 3 is moved through the slide guide 7 of the placement unit of the samples 1 in relation to the line of the passing radiation through the slot 73 in the plate 71. In this embodiment at least one detector 29 in the detector unit 25 may comprise either a mono or two-dimensional detector. When at least one detector 29 is a one-dimensional network detector, the detector unit 25 has the same configuration as in the first modification described above, but the plate 63 and at least one detector 29 in the detector unit 25 are fixed in position such that the slot 65 in the plate 63 and at least one detector 29 in the detector unit 25 are in alignment with the slot 73 in the plate 71 in the radiation generating unit 16.

In the preferred embodiment described above, the radiation generating unit 16 is configured to provide radiation from the sample 3 commonly to the imaging unit 23. As illustrated in FIG. 20, in a modification the radiation generating unit 16 is configured, by omission of the second and third mirrors 21b, 21c and the third and fourth protection plates 23c, 23d, to independently provide both, the radiation transmitted through the sample 3 in the direction from the second surface 3b to the first surface 3a and the radiation reflected from the first surface 3a of the sample 3 and both the radiation transmitted through the sample 3 in the direction from the first surface 3a to the second surface 3b and the reflected radiation from the second surface 3b of the shows 3. Correspondingly, the imaging unit 23 comprises a first polarizer 26a and at least u n first optical element 27a, in this mode at least one lens, to receive both, the radiation transmitted through the sample 3 in the direction from the second surface 3b to the first surface 3a and the radiation reflected from the first surface 3a of the sample 3 and a second polarizer 26b and at least one second optical element 27b, furthermore, in this embodiment at least one lens, to receive both radiations transmitted through the sample 3 in the direction from the first surface 3a to the second surface 3b and the radiation reflected from the second surface 3b of the sample 3, and the detector unit 25 comprises at least a first detector 29a for receiving the image formed by radiation by at least a first lens 27a and at least a second detector 29b for receiving the image formed by radiation by at least a second lens 27b. In a first configuration, at least one radiation source 17 via the beam splitting device 20 and the first mirror 21a provide radiation to the first surface 3a of the sample 3, with radiation that is prevented from passing through the second surface 3b of the sample 3 by the second protective plate 23b. In this way, at least one first detector 29a in the detector unit 25 is provided with a radiation image reflected from the first surface 3a of the sample 3 and at least one second detector 29b in the detector unit 25 is provided with an image of radiation transmitted through the sample 3 in the direction from the first surface 3a to the second surface 3b. In a second configuration, at least one radiation source 17 provides radiation via the beam splitting device 20 to the second surface 3b of the sample 3, with radiation that is prevented from passing to the first surface 3a of the sample 3 by the first protection plate 23a. In this way, at least one first detector 29a in the detector unit 25 is provided with a radiation image transmitted through the sample 3 in the direction from the second surface 3b to the first surface 3a and at least one second detector 29b in the detector unit 25 is provided with an image of radiation reflected from the second surface 3b of the sample 3. In use, the radiation is selectively provided, preferably simultaneously or alternatively, to the first and second surfaces 3a, 3b of the sample 3 to so that the detector unit 25 captures the respective transmission and reflectance images.

In the preferred embodiment described above, the radiation generating unit 16 is configured so that at least one radiation source 17 provides radiation to both, the first and second surfaces 3a, 3b of the sample 3. In a modification, as shown in FIG. illustrated in Figure 21, the radiation generating unit 16 comprises at least a first radiation source 17a which is configured to provide radiation to the first surface 3a of the sample 3 to take a measurement of the transmission from the sample 3 in the direction from the first surface 3a to the second surface 3b of the sample 3 and a measurement of the reflectance from the first surface 3a of the sample 3 and at least one second radiation source 17b which is configured to provide radiation to the second surface 3b of the sample 3 to take a measurement of the transmission from the sample 3 in the direction from the second surface 3b to the first surface 3a of the sample 3 and a measurement of the reflectance from the second surface 3b of the sample 3. The radiation generating unit 16 additionally comprises a plurality of optical elements 18a, 18b, 19a, 19b, 21a, 21b, 22a, 22b, 23a, 23b, which include the first and second polarizers 18a, 18b, the first and second diffusers 19a, 19b, the first and second mirrors 21a, 21b, the first and second lenses 22a, 22b and the first and second shield plates 23a, 23b, which allow transmission measurements to be made in both directions through the sample 3 and the reflectance measurements are made from both surfaces 3a, 3b of the sample 3. As will be described later, at least a first radiation source 17a, at least a second radiation source 17b, the first and second mirrors 21a, 21b and the first and second protection plates 23a, 23b are functionally configured to that the detector unit 25 capture the respective transmission and reflectance images. In a first configuration, at least a second radiation source 17b does not provide radiation to the second surface 3b of the sample 3 and at least a first radiation source 17a provides radiation to the first surface 3a of the sample 3, with the reflected radiation by the first surface 3a of the sample 3, which is blocked by the first protective plate 23a. In this way, the detector unit 25 is provided with a radiation image transmitted through the sample 3 in the direction from the first surface 3a to the second surface 3b. In a second configuration, at least a second radiation source 17b does not provide radiation to the second surface 3b of the sample 3 and at least a first radiation source 17a provides radiation to the first surface 3a of the sample 3, with the transmitted radiation through the sample 3 in the direction from the first surface 3a to the second surface 3b which is blocked by the second protection plate 23b. In this way, the detector unit 25 is provided via the first and second mirrors 21a, 21b of a radiation image reflected from the first surface 3a of the sample 3. In a third configuration, at least a first radiation source 17a does not provide radiation to the first surface 3a of the sample 3 and at least one second radiation source 17b provides radiation to the second surface 3b of the sample 3, with the radiation reflected from the second surface 3b of the sample 3 being blocked by the second protection plate 23b. In this way, the detector unit 25 is provided via the first and second mirrors 21a, 21b of a radiation image transmitted through the sample 3 in the direction from the second surface 3b to the first surface 3a. In a fourth configuration, at least a first radiation source 17a does not provide radiation to the first surface 3a of the sample 3 and at least a second radiation source 17b provides radiation to the second surface 3b of the sample 3, with the transmitted radiation through the sample 3 in the direction from the second surface 3b towards the first surface 3a which is blocked by the first protective plate 23a. In this way, the detector unit 25 is provided with a radiation image reflected from the second surface 3b of the sample 3. In use, the radiation is selectively provided, preferably simultaneously or alternatively, to the first and second surfaces 3a, 3b of Sample 3 so that the detector unit 25 captures the respective transmission and reflectance images.

Finally, of course, the present invention has been described in its preferred embodiment and can be modified in many different ways without departing from the scope of the invention as defined in the appended claims.

It is noted that in relation to this date the best method known by the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.

Having described the invention as above, it is claimed as property in the following:

Claims (63)

REGVINDICATIONS

1. A device for analyzing a sample, which is characterized in that it comprises; a unit for placing samples to place a sample; a radiation generating unit for providing at least one beam of electromagnetic radiation to each of the first and second surfaces of the sample; an imaging unit for providing at least one image from the radiation transmitted through each of the first and second surfaces of the sample; a detector unit for capturing the images provided by the imaging unit and generating signals corresponding thereto; and an analysis unit for working on the signals received from the detector unit and generating signals representative of the three-dimensional distribution of at least one component of the sample.

2. The device according to claim 1, characterized in that the unit for placing the samples comprises a sliding guide through which the samples in use pass.

3. The device according to claim 2, characterized in that the unit for placing the samples is configured so that the samples are moved in a slow manner through the sliding guide.

4. The device according to claim 2, characterized in that the sample positioning unit is configured so that the samples are moved continuously through the sliding guide.

5. The device according to any one of claims 1 to 4, characterized in that at least one of the radiation beams is collimated.

6. The device according to any one of claims 1 to 4, characterized in that at least one of the radiation beams is convergent.

7. The device according to any one of claims 1 to 4, characterized in that at least one of the radiation beams is divergent.

8. The device according to any one of claims 1 to 7, characterized in that the main axis of at least one of the radiation beams is substantially normal to the respective surface of the sample.

9. The device according to any one of claims 1 to 7, characterized in that the main axis of at least one of the radiation beams is at an angle with the respective surface of the sample.

10. The device according to any of claims 1 to 9, characterized in that at least one of the radiation beams is dimensioned to radiate substantially and completely the respective surface of the sample.

11. The device according to any one of claims 1 to 9, characterized in that at least one of the radiation beams is designed to irradiate an area smaller than that of the respective surface of the sample.

12. The device according to claim 11, characterized in that the radiation generating unit is configured so that, in use, it moves at least one of the radiation beams in at least one direction and thus sweeps with at least one of the beams of radiation. radiation over substantially all of the respective surface of the sample.

13. The device according to any of claims 1 to 12, characterized in that the first and second surfaces of the sample are opposite oriented surfaces.

14. The device according to any of claims 1 to 13, characterized in that at least one of the radiation beams is visible light.

15. The device according to any of claims 1 to 13, characterized in that at least one of the radiation beams is infra-red radiation.

16. The device according to claim 15, characterized in that the infra-red radiation is in the infra-red region nearby.

17. The device according to claim 16, characterized in that the infra-red radiation has a frequency in the range corresponding to the wavelengths from 700 to 1700 nm.

18. The device according to claims 1 to 13, characterized in that at least one of the radiation beams is X-ray radiation.

19. The device according to any of claims 1 to 18, characterized in that the radiation generating unit comprises at least one radiation source and at least one optical element.

20. The device according to claim 19, characterized in that the radiation generating unit additionally comprises a mobile diffuser in the output line of each radiation source.

21. The device according to claim 19 or 20, characterized in that the radiation generating unit additionally comprises at least one polarizer in the output line of each radiation source.

22. The device according to any of claims 19 to 21, characterized in that the radiation generating unit comprises a first radiation source, a second source of radiation and associated optical elements, each of the radiation sources provided by a beam of radiation to respectively irradiate the first and second surfaces of the sample.

23. The device according to any of claims 19 to 22, characterized in that any or each of the radiation sources comprises a laser.

24. The device according to any of claims 19 to 22, characterized in that any or each of the radiation sources comprises a light emitting diode.

25. The device according to any one of claims 1 to 24, characterized in that the imaging unit comprises at least one optical element for providing at least one radiation image transmitted through each of the first and second surfaces of the sample.

26. The device according to claim 25, characterized in that the imaging unit additionally comprises at least one polarizer for polarization of the radiation transmitted through each of the first and second surfaces of the sample.

27. The device according to claim 25 or 26, which is characterized in that the imaging unit additionally comprises at least one beam splitting device for providing a plurality of images of different frequency or band of single frequencies of radiation transmitted through each of the first and second waveform surfaces. the sample.

28. The device according to claim 27, characterized in that the beam splitting device comprises a frequency-dependent beam splitting device, which together with at least one optical element provides a plurality of images of different frequency or band of unique frequencies. of radiation transmitted through each of the first and second surfaces of the sample.

29. The device according to claim 27, characterized in that the beam splitting device comprises a non-frequency dependent beam splitting device, which separates the radiation transmitted through each of the first and second surfaces of the sample in a plurality of components, and a plurality of filters for filtering each of the respective components to provide radiation of different frequency or single frequency band, the beam splitting device and the filters together with at least one optical element that provides a plurality of images of different frequency or band of single frequencies of the radiation transmitted through each of the first and second surfaces of the sample.

30. The device according to claim 27, characterized in that the beam splitting device comprises a transmission network, which together with at least one optical element provides a plurality of images of different frequency or band of unique frequencies of the transmitted radiation to through each of the first and second surfaces of the sample.

31. The device according to claim 27, characterized in that the beam splitting device comprises a prismatic arrangement, which separates the radiation transmitted through each of the first and second surfaces of the sample into a plurality of components, and a plurality of filters to filter each of the respective components to give radiation of different frequency or band of unique frequencies, the prismatic array and the filters together with at least one optical element that provide a plurality of images of different frequency or band of unique frequencies of the radiation transmitted through each of the first and second surfaces of the sample.

32. The device according to claim 27, characterized in that the beam splitting device comprises a plurality of lenses, which separate the radiation transmitted through each of the first and second surfaces of the sample in a plurality of components, and a plurality of filters for filtering each of the respective components to give radiation of different frequency or single frequency band, the lenses and the filters together with at least one optical element that provide a plurality of images of different single frequency or frequency band from the radiation transmitted through each of the first and second surfaces of the sample.

33. The device according to any one of claims 1 to 32, characterized in that the detector unit comprises at least one detector.

34. The device according to claim 33, which is characterized in that it comprises a single detector.

35. The device according to claim 33, which is characterized in that it comprises a plurality of detectors.

36. The device according to claim 34 or 35, characterized in that the or at least one detector is a bi-dimensional network detector.

37. The device according to claim 35, characterized in that each detector is a sub-network of a network detector.

38. The device according to claim 34 or 35, characterized in that the at least one detector is a one-dimensional network detector.

39. The device according to any of claims 33 to 38, characterized in that the detector unit is configured so that in use at least one detector is moved to capture the images provided by the imaging unit.

40. The device according to any of claims 33 to 39, characterized in that at least one detector comprises one of a CMOS microelement, a CCD microelement or a focal plane network.

41. A method of analyzing a sample, which is characterized in that it comprises the steps of: provide a sample; irradiating the first and second surfaces of the sample each with at least one beam of electromagnetic radiation; forming images with the radiation transmitted through the first and second surfaces of the sample; capture the images formed with the radiation and generate signals corresponding to them; and working on the signals corresponding to the images formed with the radiation and generating signals representative of the three-dimensional distribution of at least one component in the sample.

42. The method according to claim 41, characterized in that the sample is stationary during irradiation.

43. The method according to claim 41, characterized in that the sample is mobile during irradiation.

44. The method according to any of the claims 41 to 43, which is characterized in that at least one of the radiation beams is collimated.

45. The method according to any of claims 41 to 43, characterized in that at least one of the radiation beams is convergent.

46. The method according to any of claims 41 to 43, characterized in that at least one of the radiation beams is divergent.

47. The method according to any of claims 41 to 46, characterized in that the main axis of at least one of the radiation beams is substantially normal to the respective surface of the sample.

48. The method according to any one of claims 41 to 46, characterized in that the main axis of at least one of the radiation beams is angled with the respective surface of the sample.

49. The method according to any of claims 41 to 48, characterized in that at least one of the radiation beams is dimensioned to radiate substantially the entire surface of the specimen.

50. The method according to any of claims 41 to 48, characterized in that at least one of the radiation beams is dimensioned to irradiate a smaller area than that of the respective surface of the sample and the respective surface of the sample is substantially irradiated , completely by scanning at least one of the radiation beams on it.

51. The method according to any of claims 41 to 48, characterized in that at least one of the radiation beams is sized to irradiate an area smaller than that of the respective surface of the sample and the respective surface of the sample is irradiated substantial, completely by movement of the sample to sweep at least one of the radiation beams on it.

52. The method according to claim 50 or 51, characterized in that at least one of the radiation beams is in the form of a line.

53. The method according to any of claims 41 to 52, which is characterized in that the first and second surfaces of the sample are opposite oriented surfaces.

54. The method according to any of claims 41 to 53, characterized in that the radiation comprises a single frequency, a single frequency band, a plurality of single frequencies or a plurality of frequency bands.

55. The method according to any of claims 41 to 54, characterized in that at least one of the radiation beams is continuous.

56. The method according to any of claims 41 to 54, characterized in that at least one of the radiation beams is per pulse.

57. The method according to claim 56, characterized in that the frequency or frequency band of the radiation in each pulse is different.

58. The method according to any of claims 41 to 57, characterized in that at least one of the radiation beams is visible light.

59. The method according to any of claims 41 to 57, characterized in that at least one of the radiation beams is infra-red radiation.

60. The method according to claim 59, which is characterized in that the infra-red radiation is in the near infra-red region.

61. The method according to claim 60, characterized in that the infra-red region has a frequency in the range corresponding to the wavelengths from 700 to 1700 nm.

62. The method according to any of the claims 41 to 57, which is characterized in that at least one of the radiation beams is X-ray radiation.

63. The method according to any of claims 41 to 62, characterized in that the step of forming images with the radiation comprises the step of providing a plurality of images of different frequency or band of unique frequencies of the radiation transmitted through each one of the first and second surfaces of the sample.