The present disclosure relates to an optical system for a sample processing instrument such as a flow cytometer/analyzer, and in particular to an optical system including multiple light sources and a sample processing instrument including the optical system.
This section only provides background information related to the present disclosure, which is not necessarily the prior art.
A sample processing instrument is generally used to analyze liquid samples including small suspended particles (e.g., biological particles, non-biological particles) or cells and/or to sort the particles or cells therein. A laser diode is often used as the light source for the optical system of the sample processing instrument. The beam emitted from the laser diode is focused inside the detection channel of the flow cell of the sample processing instrument. When a particle or cell in the sample is passing through the detection channel, it is illuminated by the light beam, thereby emitting fluorescent or scattered light for detection.
Due to a large divergence of the laser diode (also referred to herein as a laser light source), the beam emitted from the laser diode is required to be collimated. The size of the collimated laser beam decides the size of the beam focused within the flow cell. Therefore, the consistency of the laser beams is very important for the detection of samples. For example, for the same batch of sample processing instruments, the consistency of sample analysis results is very important. For example, it may be desired to have consistency of laser beams with the same wavelength in different sample processing instruments. Moreover, for a single sample processing instrument having multiple laser light sources, it may sometimes be desired to have consistency (e.g., in size or focusing position) of beams emitted from all the laser sources.
However, a laser diode is manufactured with a certain divergence tolerance, and different laser diodes have different divergence tolerances. To meet the requirements of detection, a laser diode is selected with a specific divergence tolerance. In addition, when consistency of the laser beams is not good, the laser module may need to be updated or replaced. Thus, the labor time of the laser diode is wasted, and the cost is too high.
A general summary of the present disclosure is provided in this section, rather than the full scope of the present disclosure or a comprehensive disclosure of all features of the present disclosure.
In view of the above problems of the existing optical system of the sample processing instrument, an object of the present application is to provide an optical system and a sample processing instrument including a reshaping device. The light emitted from the laser light source can be shaped by the reshaping device so that the reshaped beam has a desired size in a predetermined direction. It is also possible to reshape the light emitted from at least one laser light source by the reshaping device so that multiple laser beams have the same size in a predetermined direction, thereby improving the detection performance.
The optical system according to the present disclosure is adapted to sample processing instruments. For example, the optical system according to the present disclosure can enable the beams of various laser sources in a single sample processing instrument using the optical system to have a uniform size after reshaping. For example, the optical system according to the present disclosure can enable the size of the beam reshaped by the optical system to be the same as the size of the beam of a certain laser source of another different sample processing instrument.
According to an aspect of the present disclosure, there is provided an optical system for a sample processing instrument including a flow cell having a detection channel for passage and detection of a sample. The optical system includes: a laser source; a collimating device configured to collimate light beam emitted from the laser source; a focusing lens configured to focus the light beam coming from the laser source on a point within the detection channel; and a reshaping device disposed between the collimating device and the focusing lens and configured to reshape a light spot of the collimated light beam. The reshaping devices includes a first prism pair including two prisms, and the two prisms are adjustable relative to each other, so that the light beam of the laser source has a predetermined size in a first direction.
According to the optical system of the present disclosure, the beams of all laser light sources of a same sample processing instrument can have the same size through the reshaping devices, or the beam reshaped by the optical system can have the same size as the beam of a laser source of any other sample processing instrument. It is thus possible to avoid replacing laser light sources or laser modules whose divergence angles do not meet the requirements. In this way, more laser light sources can be adapted to the sample processing instrument, thereby significantly reducing costs and saving time.
In some embodiments according to the present disclosure, the reshaping device further includes a second prism pair including two prisms. The two prisms are adjustable relative to each other, so that the light beam of the laser source has a predetermined size in a second direction perpendicular to the first direction.
In some embodiments according to the present disclosure, the two prisms of the prism pare or each prism pair can be rotated and/or translated relative to each other.
In some embodiments according to the present disclosure, the two prisms of the prism pare or each prism pair are made of the same material.
In some embodiments according to the present disclosure, the material has a refractive index ranging from 1.4 to 1.8.
In some embodiments according to the present disclosure, each of the two prisms of the prism pare or each prism pair has an incident surface where the light beam enters the prism and an exit surface where the light beam exits the prism, and the two prisms of the prism pare or each prism pair are arranged to have the same incident angle at the incident surfaces and the same exit angle at the exit surfaces with respect to the same light beam.
In some embodiments according to the present disclosure, the two prisms of the prism pare or each prism pair have the same structure.
In some embodiments according to the present disclosure, an angle between the incident surface and the exit surface of each prism is in the range of 20° to 45°.
In some embodiments according to the present disclosure, an anti-reflection film is coated on the incident surface and/or the exit surface.
In some embodiments according to the present disclosure, the anti-reflection film on one of the incident surface and the exit surface is designed or selected for an incident angle or an exit angle of 0° to 10°, and the anti-reflection film on the other of the incident surface and the exit surface is designed or selected for an incident angle or an exit angle of 40° to 60°.
In some embodiments according to the present disclosure, the prism pare or each prism pair is configured such that the size ratio of the light beam after exiting the prism pair to the light beam before entering the prism pair is between 0.5 and 2.75.
In some embodiments according to the present disclosure, a focus adjustment device is provided between the laser source and the focusing lens, and the focus adjustment device is configured to adjust focus of the light beam emitted from the laser source to a predetermined position within the detection channel.
In some embodiments according to the present disclosure, the focus adjustment device is composed of two optical parts, and the distance between the two optical parts is adjustable. Each of the two optical parts is selected from one of a convex lens, a concave lens, a cylindrical lens, a doublet lens, or a lens group.
In some embodiments according to the present disclosure, the optical system includes a plurality of laser sources emitting the light beams having mutually different wavelengths, and a beam-combination mirror is provided between each laser source and the focusing lens.
In some embodiments according to the present disclosure, the reshaping devices and the focus adjustment devices are disposed between each laser light sources and the respective beam combiners.
A sample processing instrument is provided according to another aspect of the present disclosure. The sample processing instrument includes the above optical system and a flow cell. The flow cell has the detection channel through which a liquid sample flows, and the optical system is configured to detect particles in the liquid sample.
The above and other objects, features and advantages of the present disclosure will be more fully understood from the detailed description given below and the accompanying drawings, which are given by way of illustration only and therefore are not considered to limit the present disclosure.
The features and advantages of one or more embodiments of the present disclosure will become more readily understood from the following description with reference to the accompanying drawings in which:
The following detailed description of the present disclosure is for explanation only and is by no means intended to limit the present disclosure and the applications or usages thereof. The implementations described in this specification are not exhaustive and are merely some of many possible implementations. Exemplary embodiments may be embodied in many different forms and should not be construed as limiting the scope of the present disclosure. In some example embodiments, well-known processes, well-known device structures, and well-known technologies may not be described in detail.
The optical system and sample processing instrument according to the present disclosure are suitable for detection or sorting of liquid samples containing biological particles (e.g., extracellular vesicles) or non-biological particles (e.g., beads). The optical system and the sample processing instrument according to the present disclosure will be described below with reference to the accompanying drawings. In several drawings, similar reference numerals refer to similar parts and components.
In the sample processing instrument 1, the sheath fluid and the sample are delivered to the flow cell 20 through fluid piping (not shown). In the flow cell 20, the sheath fluid wraps the sample, so that the particles P contained in the sample can flow through the detection channel 21 of the flow cell 20 in a single row linearly. The light beams emitted by the light sources in the optical system 10 are focused on a point within the detection channel 21. When the sample is flowing through the detection channel 21, the particles P contained in the sample pass through the focal point of the light beams and are irradiated by the light beams at the focal point. Under the illumination of the light beams, the particles P may emit fluorescent light or scattered light. By collecting the fluorescence or scattered light emitted from the particles P, and by processing and analyzing the signals of the fluorescence or scattered light, the information of the detected particles P can be obtained.
Herein, for the convenience of description, the extension axis of the detection channel 21 of the flow cell 20 (i.e., the flow direction of the sample) is defined as the Z axis; the central axis (or optical axis) of the light beam focused in the detection channel 21 is defined as the Y axis; and the axis perpendicular to the Z axis and Y axis is defined as the X axis.
The optical system 10 shown in
In the example shown, two laser light sources 11a to 11d are arranged in parallel. It should be understood that the number, type, and arrangement of laser light sources are not limited to the specific example shown, but may be changed as required. For example, the optical system may include three, four, or any other suitable number of laser light sources.
The optical system 10 further includes a focusing lens 19. The light beams emitted from light sources 11a and 11b are focused via focusing lens 19 on the same detection position in detection channel 21 of flow cell 20, and the detection position may be referred to as the focus point or interrogation point.
The optical system 10 further includes collimating devices 12a and 12b. The collimating devices 12a and 12b are used for collimating the light beams emitted by the laser light sources 11a and 11b, respectively. The light beams emitted from the laser light sources 11a and 11b are generally divergent with a certain angle. The light beams emitted from the laser light sources 11a and 11b can be changed into parallel light beams with a desired size by the collimating devices 12a and 12b.
The optical system 10 further includes reshaping devices 14a and 14b. The reshaping devices 14a and 14b are arranged between the respective collimating devices 12a and 12b and the focusing lens 19. The reshaping devices 14a and 14b are used to reshape the collimated light beams so that the light spot focused on the particle P has a uniform size in the X-axis direction.
Laser light sources (laser diodes) are manufactured with a certain divergence tolerance, and different laser diodes have different divergence tolerances. Even after the beams are collimated by the collimating devices 12a and 12b, the collimated beams still have size differences. The reshaping devices 14a and 14b can eliminate or reduce the size difference between the collimated beams. In the embodiment shown in
The optical system 10 further includes focus adjustment devices 16a and 16b. The focus adjustment devices 16a and 16b are provided between the respective laser light sources 11a and 11b and the focusing lens 19. The focus adjustment devices 16a and 16b are used to adjust the focus of the light beams emitted from the laser light sources 11a and 11b to a predetermined position (for example, the center position in the Y-axis direction) within the detection channel 21, that is, adjust the waist position of the focused beam in the Y-axis direction. The specific structures of the focus adjustment devices 16a and 16b will be described in detail later with reference to
The optical system 10 further includes beam combiners 18a and 18b. The beam combiners 18a and 18b are provided between the respective laser light sources 11a and 11b and the focusing lens 19. Each of the beam combiners 18a and 18b is used to reflect the light beam of the corresponding laser light source 11a or 11b, while allowing the light beam of the other laser light source to pass through. The beam combiners 18a and 18b can be selected and arranged according to the wavelengths of the light beams emitted by the corresponding laser light sources 11a and 11b. For example, beam combiner 18a may be configured to reflect light of wavelengths emitted by laser light source 11b; and the beam combiner 18b may be configured to reflect the light of the wavelength emitted by the laser light source 11b and to transmit the light of the wavelength emitted by the laser light source 11a.
The light beams emitted by the light sources 11a and 11b are formed into collinear light beams after being reflected or transmitted by the beam combiners 18a and 18b. A collinear light beam refers to having the same optical axis (optical axis O as shown in
The various components of the optical system according to the present disclosure and the functions of the various components are summarized above with reference to
For example, in the embodiment shown in
For example, in the embodiment shown in
For example, in the embodiment shown in
For example, the laser light sources 11a and 11b may have different arrangements of the same optical components or may have different optical components. For example, the focus adjustment device 16a may be disposed between the laser light source 11a and the reshaping device 13a, and the focus adjustment device 16b may be disposed between the reshaping device 13b and the beam combiner 18b. For example, reshaping devices or focus adjustment devices may be provided only for the laser light source 11a or 11b. For example, the beam combiner 18a may be a mirror having only a reflective function, different from the beam combiner 18b.
The reshaping device 100 according to the present disclosure will be described below with reference to
Referring to
The reshaping device 100 includes a first prism 110 and a second prism 120. The first prism 110 has an incident surface 111 where the incident light beam IB enters the first prism 110 and an exit surface 112 where the incident light beam IB exits the first prism 110. An acute angle θ1 is formed between the incident surface 111 and the exit surface 112. Similarly, the second prism 120 has an incident surface 121 where the light beam enters the second prism 120 and an exit surface 122 where the light beam exits the second prism 120. An acute angle θ2 is formed between the incident surface 121 and the exit surface 122. The acute angle θ1 or θ2 of the first prism 110 or the second prism 120 can change the size ratio of the outgoing light beam OB to the incident light beam IB. In other words, the acute angles θ1 and θ2 of the first prism 110 and the second prism 120 may be designed or selected according to the desired size ratio. For example, the acute angles θ1 and θ2 may be in the range of about 20° to 45°. Optionally, the acute angles θ1 and θ2 may be about 30°.
Furthermore, if the materials of the first prism 110 or the second prism 120 are different, they may have different refractive indexes. Therefore, the material of the first prism 110 or the second prism 120 can also change the size ratio of the outgoing light beam OB to the incident light beam IB. In other words, materials of the first prism 110 and the second prism 120 may be selected according to a desired size ratio. For example, the first prism 110 or the second prism 120 may be made of a material having a refractive index of about 1.4 to 1.8, such as fused silica, N-BK7 or equivalent material, LF5 or equivalent material, SF11 or equivalent material.
The first prism 110 and the second prism 120 may be made of the same material and may have the same structure (especially, the acute angles θ1 and θ2 have the same value). The first prism 110 and the second prism 120 may be oppositely arranged. The incident angles at the incident surfaces 111 and 121 may be the same, and the exit angles at the exit surfaces 112 and 122 may also be the same, thereby ensuring that the propagation direction of the outgoing light beam OB is parallel to the propagation direction of the incident light beam IB.
For ease of description, a base line BL that is perpendicular to the incident light beam IB is introduced. The base line BL is shown in dotted line. The incident surface 111 is deflected by an angle φ with respect to the base line BL. The angle φ is an acute angle and corresponds to the incidence angle of the incident light beam IB relative to the normal direction of incident surface 111. For convenience of description, the angle φ at which the incident surface 111 deflects clockwise with respect to the base line BL is defined as positive (as shown in
The deflection angle φ may be determined based on the deflective index of the prism, the angle formed between the incident surface and exit surface, the size ratio of outgoing beam to incident beam, etc. By determining the deflection angle φ, the prism may be appropriately placed relative to the base line BL (i.e., incident beam) in position.
How to set the prism pair will be described below with reference to
According to the graph of
Then, according to the graph of
The first prism 110 or the second prism 120 is adjustable relative to each other, so that the beams of the corresponding laser light sources have the same size in the first direction as beams of the other laser light sources. Referring to
The first prism and the second prism of each reshaping device (each prism pair) can be rotated relative to each other (as indicated by the arrows in
The first prism and the second prism of each reshaping device may be translated relative to each other. In case that the first prism and the second prism are translated (for example, along the horizontal or vertical direction), the position of the outgoing light beam OB may change (for example, along the direction perpendicular to the light beam), but the size of the outgoing light beam OB may not change substantially.
Since the first prism and the second prism can be adjusted easily or in real time, the reshaping device according to the present disclosure can be applied to various laser light sources and can make the spot projected on the particle have a uniform size in at least one direction.
According to the reshaping device of the present disclosure, an anti-reflection film may also be coated on the incident surface and/or the exit surface of the prism to reduce light beam loss. The anti-reflection film can reduce the intensity of reflected light, thereby increasing the intensity of transmitted light. The anti-reflection film can be designed or selected according to the angle of incidence or angle of exit. For example, the anti-reflection film on one of the incident surface and the exit surface may be designed or selected for an incident angle or exit angle of 0 to 10 degrees, whereas the anti-reflection film on the other of the incident surface and the exit surface may be designed or selected for an incident angle or exit angle of 40 to 60 degrees. In addition to the incident angle and the exit angle, the design or selection of the anti-reflection film may also consider factors such as the wavelength of the laser light source, the material of the prism, or the angle between the incident surface and the exit surface.
The focus adjustment device 500 according to the present disclosure will be described below with reference to
Referring to
In
In
In the example shown in
The light beam incident to the focus adjustment device 500 may be parallel, or may be divergent. Thus, the focus adjustment device 500 may be provided at any suitable position between the laser light source and the focusing lens, for example, between the laser light source and the beam combiner in
As described above, the focusing spots of the light beams of multiple laser light sources can have the same size in the predetermined direction by the reshaping device, or the light beams of multiple laser light sources can be focused on the same predetermined position (i.e., the desired interrogation point) by the focus adjustment device, so that the detection accuracy can be improved.
It should be understood that the adjustment or movement of the optical device described above can be done manually, or can be done electronically using a computing device (e.g., a controller) associated with one or more actuators coupled to the optical device.
It should be understood that the reshaping device or the focus adjustment device can be integrated with the laser light source in the laser module, or can be set independently of the laser module.
The optical system of the sample processing instrument should not be limited to the specific examples described herein or shown in the drawings, but may vary according to actual detection requirements. For example, optical elements can be replaced, reduced or added depending on detection performance requirements.
Although the present application has been described with reference to exemplary embodiments, it should be understood that the present application is not limited to the specific embodiments described and illustrated herein. Without departing from the scope defined by the claims, those skilled in the art can make various changes to the exemplary embodiments. Provided that there is no contradiction, the features in the various embodiments can be combined with each other. Alternatively, a certain feature in the embodiment may also be omitted.
Number | Date | Country | Kind |
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202210115333.3 | Jan 2022 | CN | national |
Filing Document | Filing Date | Country | Kind |
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PCT/CN2023/072062 | 1/13/2023 | WO |