Microfluidic chip and detection system for assessing the biological effects of radioactive particles

Abstract

The present disclosure discloses a microfluidic chip, comprising: at least one fixing device and at least one microfluidic channel; the at least one fixing device is located on the microfluidic chip and used for fixing radioactive particles; the at least one microfluidic channel is arranged on the microfluidic chip and used for culturing at least one of microorganisms, cells or biological tissues; the distance between each microfluidic channel and the first fixing device is different; the first fixing device is any one of the at least one fixing device; the radiation information of at least one of microorganisms, cells or biological tissues in the at least one microfluidic channel is used for confirming the influence of the radioactive particles placed in the at least one fixing device on at least one of microorganisms, cells or biological tissues with different distances from the radioactive particles.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to the field of radioactive particle detection and evaluation, in particular to a microfluidic chip and a detection system for accurately evaluating the biological dose-effect relationship of radioactive particle therapy at different radiation distances. BACKGROUND

[0002] The radioactive particles emit rays with radiation, which have important uses in various fields; in particular, the rays with radiation can directly act on DNA to break DNA chains, and can also ionize the liquid in cell tissues to generate free radicals; therefore, it is an urgent technical problem to evaluate the radiation performance of radioactive particles and understand the influence of radioactive particles on cells or microorganisms. SUMMARY

[0003] The present disclosure provides a microfluidic chip and a detection system for evaluating the biological radiation effect of radioactive particles to at least solve the above technical problems.

[0004] According to an aspect of the present disclosure, a microfluidic chip is provided, comprising: at least one fixing device and at least one microfluidic channel;

[0005] The at least one fixing device is located on the microfluidic chip and is used to fix radioactive particles;

[0006] The at least one microfluidic channel is arranged on the microfluidic chip and is used to culture at least one of cells, microorganisms, and biological tissues;

[0007] The distance between each microfluidic channel and the first fixing device is different; the first fixing device is any one of the at least one fixing device;

[0008] The radiation information of at least one of cells, microorganisms, and biological tissues in the at least one microfluidic channel is used to confirm the influence of the radioactive particles placed in the at least one fixing device on at least one of cells, microorganisms, and biological tissues at different distances from the radioactive particles.

[0009] In the above scheme, the at least one microfluidic channel has one of the following shapes:

[0010] Linear, curved, or zigzag;

[0011] The distance between adjacent two microfluidic channels is the same or different.

[0012] In the above scheme, the two ends of each microfluidic channel are respectively provided with an inlet and an outlet.

[0013] In the above scheme, a communication structure is arranged between adjacent two microfluidic channels.

[0014] The fluid in at least one microfluidic channel flows into different microfluidic channels through the communication structure.

[0015] In the above solution, the first fixing device and the at least one microfluidic channel are located on the same horizontal plane.

[0016] Alternatively, the first fixing device and the at least one microfluidic channel are located on different horizontal planes.

[0017] In the above solution, the first fixing device is arranged inside a first microfluidic channel of the at least one microfluidic channel, and in the case that there is fluid in the first microfluidic channel, the radioactive particle is in contact with the fluid in the first microfluidic channel, or the radioactive particle is not in contact with the fluid in the first microfluidic channel.

[0018] In the above solution, the cells include at least one of human cells, animal cells, or plant cells.

[0019] The microorganisms include at least one of bacteria, yeast, intestinal microorganisms, soil microorganisms, viruses, microalgae, viruses, microalgae, nematodes, fruit flies, or zebrafish larvae.

[0020] The biological tissues include at least one of biological biopsy tissues, organoids, or 3D cell cultures.

[0021] According to another aspect of the present disclosure, a detection system for evaluating the biological radiation effect of radioactive particles is provided, including a microfluidic chip, a radiation detector, and a radioactive particle.

[0022] The radioactive particle is arranged in the microfluidic chip and is used to emit radiation.

[0023] The microfluidic chip is arranged with at least one of cells, microorganisms, or biological tissues.

[0024] The radiation detector is used to detect the radiation information of at least one of the cells, microorganisms, or biological tissues in the microfluidic chip after being irradiated by the radiation.

[0025] In the above solution, the microfluidic chip includes at least one fixing device and at least one microfluidic channel.

[0026] The at least one fixing device is arranged on the microfluidic chip and is used to fix the radioactive particle.

[0027] The at least one microfluidic channel is arranged on the microfluidic chip and is used to culture at least one of cells, microorganisms, or biological tissues.

[0028] The distance between each microfluidic channel and the first fixing device is different, and the first fixing device is any one of the at least one fixing device.

[0029] In the above aspect, the at least one microfluidic channel is one of the following shapes:

[0030] a straight line, a curve or a broken line;

[0031] The distance between the adjacent two microfluidic channels is the same or different.

[0032] In the above aspect, the first fixing device and the at least one microfluidic channel are located on the same horizontal plane.

[0033] Alternatively, the first fixing device and the at least one microfluidic channel are located on different horizontal planes.

[0034] In the above aspect, the first fixing device is arranged inside a first microfluidic channel of the at least one microfluidic channel, and in the case that there is a fluid in the first microfluidic channel, the radioactive particle is in contact with the fluid in the first microfluidic channel, or the radioactive particle is not in contact with the fluid in the first microfluidic channel.

[0035] In the above aspect, the system further comprises a fluid operation device.

[0036] The fluid operation device is connected to the inlet or outlet of the at least one microfluidic channel included in the microfluidic chip, and is used for at least one of injection, mixing and collection of fluid.

[0037] The fluid is used for culturing at least one of cells, microorganisms or biological tissues in the microfluidic channel.

[0038] In the above aspect, the system further comprises a detection device.

[0039] The detection device is used for detecting characteristic information of at least one of cells, microorganisms or biological tissues in the at least one microfluidic channel.

[0040] In the above aspect, the characteristic information at least includes one of the following:

[0041] activity information, metabolic information, cell proliferation information, cell number information, pH value information, oxygen distribution information and apoptosis information.

[0042] The microfluidic chip and the detection system for evaluating the biological radiation effect of radioactive particles provided by the present disclosure, the radioactive particles are arranged in the microfluidic chip for emitting rays; at least one of cells, microorganisms or biological tissues is placed in the microfluidic chip; the radiation detector is used for detecting the radiation information of at least one of cells, microorganisms or biological tissues in the microfluidic chip after being radiated by the rays; the microfluidic chip comprises at least one fixing device and at least one microfluidic channel; the at least one fixing device is located on the microfluidic chip and used for fixing the radioactive particles; the at least one microfluidic channel is arranged on the microfluidic chip and used for culturing at least one of cells, microorganisms or biological tissues; the distance between each microfluidic channel and the first fixing device is different; the first fixing device is any one of the at least one fixing device. The radiation performance of the radioactive particles can be accurately evaluated.

[0043] It should be understood that the content described in this part is not intended to identify key or important features of the embodiments of the present disclosure, nor to limit the scope of the present disclosure. Other features of the present disclosure will become apparent from the following description. BRIEF DESCRIPTION OF DRAWINGS

[0044] The accompanying drawings are used to better understand the present scheme and do not limit the present disclosure. Among them:

[0045] Figure 1 An optional flow diagram of the microfluidic chip provided by the embodiments of the present disclosure is shown;

[0046] Figure 2 Another optional flow diagram of the microfluidic chip provided by the embodiments of the present disclosure is shown;

[0047] Figure 3 An optional structural diagram of the detection system for evaluating the biological radiation effect of radioactive particles provided by the embodiments of the present disclosure is shown;

[0048] Figure 4 An optional application diagram of the detection system for evaluating the biological radiation effect of radioactive particles provided by the embodiments of the present disclosure is shown;

[0049] Figure 5 An application flow diagram of the detection system for evaluating the biological radiation effect of radioactive particles provided by the embodiments of the present disclosure is shown. DETAILED DESCRIPTION

[0050] Exemplary embodiments of the present disclosure are described herein with reference to the accompanying drawings, which are cited by way of example only. The various details of the embodiments of the present disclosure are described with reference to the accompanying drawings, which are cited by way of example only. Therefore, those of ordinary skill in the art should recognize that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of the present disclosure. Also, descriptions of well-known functions and structures are omitted in the following description for clarity and conciseness.

[0051] Radiation therapy is one of the main means of tumor treatment. There are various ways of radiation therapy, for example, alpha particles, beta particles (positrons and negative electrons), gamma rays generated by a nuclide probe can be used for radiation therapy; X-rays, gamma rays, proton beams generated by large medical instruments can also be used for radiation therapy, and different radiation sources have different medical physical properties. Among them, the principle of radioactive particle tumor treatment is to use the radiation physical properties of radioactive isotopes for treatment. Since the tissue half-value layer is only 1-2 centimeters (cm), it will not cause internal irradiation to the main organs in the distal end, so radioactive particle implantation therapy has become an effective and widely used brachytherapy method.

[0052] Radioactive particle therapy for tumors, like other radiation therapies, requires detailed radiation planning before surgery to target and kill tumors as accurately as possible while minimizing unnecessary damage to surrounding normal tissues. When developing a radiation therapy plan, the tumor area needs to be outlined based on the case images and case data, and the number of radioactive particles implanted, the position, the distance between the radioactive particles and the tumor or major organs, and other specific plans need to be determined. The development of these plans itself requires a comprehensive understanding of the dose-effect relationship of radioactive particle therapy. In fact, even if the dose-effect of radioactive particle therapy is accurately assessed in advance, some patients still have good therapeutic effects, while others have no significant therapeutic effects. There are many reasons related to this, such as whether the implementation plan of the radiation therapy is most suitable for the case, the bystander effect of radiation therapy, the individual genetic and protein resistance levels of the patient, etc. To better solve the above-mentioned clinical problems, a more accurate and comprehensive understanding of the mechanisms of radioactive particle therapy is needed. Objectively, a method for quantitatively evaluating the dose-effect relationship of radioactive particles for individual treatment is needed.

[0053] In related schemes, the in vivo detection scheme by directly implanting radioactive particles into the human body or mice has many achievements and contributions in therapeutic effect and related biological detection. However, due to the complexity of in vivo research and the influence of multiple factors, it is still difficult to understand the role of certain factors in radioactive particle therapy. At the same time, the number of indicators that can be monitored in in vivo research is relatively limited, and there are also limitations in sampling time points and individual differences of different mice. Therefore, establishing an in vitro model that simulates in vivo conditions and simplifies related influencing factors is beneficial to quickly and directly understand the response of related particle therapy, and provides individualized diagnosis and treatment information for radioactive particle therapy of clinical patients. Through literature retrieval, there is currently no effective in vitro detection system. Therefore, the present disclosure provides a microfluidic chip and a detection system for evaluating the biological radiation effect of radioactive particles, which is used for mechanism research and rapid therapeutic effect evaluation of individualized samples of radioactive particle therapy.

[0054] The biological effect of radioactive particles on living cells at different distances has no non-invasive, quantifiable and sustainable detection and monitoring method. In addition, the response of different individuals to radioactive particle therapy is very different, and even if the particle implantation scheme is accurately planned according to the tumor volume in vivo, sometimes the optimal radiotherapy cannot be achieved.

[0055] In view of the defects in the related art, the embodiments of the present disclosure provide a microfluidic chip and a detection system for evaluating the biological radiation effect of radioactive particles to at least overcome the above-mentioned defects.

[0056] Figure 1 An optional flowchart of a microfluidic chip provided by the embodiments of the present disclosure is shown, Figure 2 Another optional flowchart of a microfluidic chip provided by the embodiments of the present disclosure is shown, which will be described according to each part.

[0057] In some embodiments, the microfluidic chip 100 includes at least one fixing device 101 and at least one microfluidic channel 102. Figure 1 And Figure 2 In the above, three microfluidic channels are shown.

[0058] The at least one fixing device 101 is located on the microfluidic chip 100 and is used for fixing radioactive particles; the fixing device 101 can be a groove on the microfluidic chip 100, and the radioactive particles are fixed on the fixing device 101 by embedding the groove (as shown in Figure 1 The fixing device 101 can also be a protruding device on the microfluidic chip 100, and the radioactive particles are fixed on the fixing device 101 by pasting, embedding or the like.

[0059] The at least one microfluidic channel 102 is arranged on the microfluidic chip 100, and is used for culturing at least one of cells, microorganisms or biological tissues; wherein the at least one microfluidic channel can be a recessed channel embedded in the microfluidic chip 100; or the at least one microfluidic channel can also be a channel fixed on one plane of the microfluidic chip 100 (the bottom of the channel is fixed on the microfluidic chip 100, and the wall of the channel is perpendicular to one plane of the microfluidic chip 100); or the at least one microfluidic channel can be a bonded structure, that is, the at least one microfluidic channel is partially embedded in the microfluidic chip 100 (as shown in the partial view of the microfluidic chip 100), and the other part protrudes from the microfluidic chip 100 (as shown in the partial view of the microfluidic chip 100), and the side wall of the at least one microfluidic channel higher than the microfluidic chip 100 is perpendicular to one plane of the microfluidic chip 100; in this case, the size ratio of the part of the at least one microfluidic channel embedded in the microfluidic chip 100 to the other part higher than the microfluidic chip 100 can be any ratio according to actual needs. Figure 1 and Figure 2 A schematic view of the microfluidic channel embedded in the microfluidic chip 100 is shown.

[0060] The distance between each microfluidic channel 102 and the first fixing device 1011 is different; the first fixing device 1011 is any one of the at least one fixing device 101;

[0061] The radiation information of at least one of cells, microorganisms or biological tissues in the at least one microfluidic channel 102 is used to confirm the influence of the radioactive particles placed in the at least one fixing device 101 on at least one of cells, microorganisms or biological tissues at different distances from the radioactive particles.

[0062] In some embodiments, the at least one microfluidic channel 102 has one of the following shapes: straight line type, curved type or broken line shape; wherein the distance between adjacent two microfluidic channels is the same or different.

[0063] In other embodiments, the at least one microfluidic channel 102 is provided with an inlet and an outlet at two ends respectively; wherein the inlet can be used to inject liquid into the microfluidic channel; and the outlet can be used to collect the liquid in the microfluidic channel. Optionally, the liquid in the at least one microfluidic channel 102 is collected through the outlet, and the characteristic information of at least one of cells, microorganisms or biological tissues in the at least one microfluidic channel is detected. Figure 1 and Figure 2 Only the inlet or outlet of the microfluidic channel located at the outermost side is identified in the figure, and those skilled in the art can understand that the other microfluidic channels are also provided with inlets and outlets; from Figure 1or Figure 2 It can be concluded that two sections of the micro-channel are provided with ports, when one of the ports is an inlet, the other port is an outlet.

[0064] As shown in Figure 1 and Figure 2 , the micro-channel in the figure is of a curved type; it should be understood that Figure 1 and Figure 2 are only schematic and do not serve to limit the protection scope of the micro-fluidic chip provided by the present disclosure.

[0065] In some optional embodiments, a communication structure can also be provided between two adjacent micro-channels 102; the fluid in at least one micro-channel flows into different micro-channels 102 through the communication structure. When the liquid in the micro-channel 102 is detected subsequently, the communication structure between the micro-channels 102 can better simulate the motion state of at least one of the cells, microorganisms or biological tissues in a specific scenario, so as to obtain more accurate detection results.

[0066] Further, if the at least one micro-channel 102 is embedded in the micro-fluidic chip in the form of a groove, the communication structure can be a groove embedded in the micro-fluidic chip; if the at least one micro-channel 102 is a channel fixed on one plane of the micro-fluidic chip 100, the communication structure can be a groove embedded in the micro-fluidic chip (correspondingly, the bottom of the micro-channel is connected with the communication structure, so that the liquid in the micro-channel can flow into the communication structure or flow into other micro-channels through the communication structure); or, the communication structure can also be a channel type structure, connecting two micro-channels through the side wall of the micro-channel (such as providing an opening of an unlimited shape on the side wall of the micro-channel, connecting two micro-channels through the opening and the pipe, groove), the bottom of the communication structure can be fixed on the micro-fluidic chip or can not be fixed on the micro-fluidic chip; if the at least one micro-channel 102 is a bonding structure, the communication structure can be a groove embedded in the micro-fluidic chip, and can also be a channel type structure, connecting two micro-channels through the side wall of the at least one micro-channel; it can also be a combination of the embedded structure and the channel type structure, that is, the communication structure is partially embedded in the micro-fluidic chip and partially connects two micro-channels through the side wall of the micro-channel.

[0067] In some optional embodiments, the first fixing device 101 and the at least one micro-channel 102 are located on the same horizontal plane; or, the first fixing device 101 and the at least one micro-channel 102 are located on different horizontal planes.

[0068] In specific implementation, if the microfluidic chip 100 is a two-dimensional microfluidic chip, the first fixing device 101 and the at least one microfluidic channel 102 are located on the same horizontal plane; or, the first fixing device 101 and the at least one microfluidic channel 102 are located on different horizontal planes.

[0069] As shown in FIG. 1, the first fixing device 101 is a groove embedded in the microfluidic chip 100, and the first fixing device 101 and the at least one microfluidic channel 102 are both embedded in the microfluidic chip 100 through the groove. After the radioactive particle is embedded in the first fixing device 101, it is located on the same horizontal plane as the at least one microfluidic channel 102. Figure 1 As shown in FIG. 2, the first fixing device 101 is fixed on the surface of the microfluidic chip 100, and the at least one microfluidic channel is embedded in the microfluidic chip. The first fixing device 101 and the at least one microfluidic channel 102 are not on the same horizontal plane; the radioactive particle is placed on the microfluidic chip 100 vertically to the plane on which the microfluidic chip 100 is located, and the radioactive particle and the at least one microfluidic channel 102 are located on different horizontal planes. Alternatively, the first fixing device 100 is arranged outside the microfluidic chip 100, such as being suspended or arranged outside the microfluidic chip through a support column, so that the first fixing device 101 and the at least one microfluidic channel 102 are no longer on the same horizontal plane; after the radioactive particle is placed in the first fixing device, it is located above or below the at least one microfluidic channel 102. Figure 2 Further, if the microfluidic chip 100 includes at least one fixing device, the at least one fixing device can all be located on the same horizontal plane as the at least one microfluidic channel 102; or all be located on different horizontal planes from the at least one microfluidic channel 102; or part of them be located on the same horizontal plane as the at least one microfluidic channel 102 and part of them be located on different horizontal planes from the at least one microfluidic channel 102.

[0070] In some embodiments, the first fixing device can also be arranged inside the first microfluidic channel of the at least one microfluidic channel. In the case that there is fluid in the first microfluidic channel, the radioactive particle is in contact with the fluid in the first microfluidic channel, or the radioactive particle is not in contact with the fluid in the first microfluidic channel. The first microfluidic channel can be any one of the at least one microfluidic channel, or a microfluidic channel arranged at the center of the circle corresponding to other microfluidic channels. Further, the first microfluidic channel can be circular, annular or any shape.

[0071]

[0072] ​In some optional embodiments, the first microfluidic channel can be a microfluidic channel arranged at the center of the circle corresponding to other microfluidic channels, and the first microfluidic channel and other microfluidic channels arranged according to the same interval or different intervals can be arranged from the center to the edge of the microfluidic chip. In this case, the first microfluidic channel can be a closed flow field (similar to a pool) of any shape, and the first fixing device is arranged inside the first microfluidic channel. In the case that there is fluid in the first microfluidic channel, the radioactive particle is in contact with the fluid in the first microfluidic channel, or the radioactive particle is not in contact with the fluid in the first microfluidic channel.

[0073] Alternatively, in some optional embodiments, the first microfluidic channel can be any microfluidic channel, and the first fixing device can be arranged inside the first microfluidic channel. In the case that there is fluid in the first microfluidic channel, the radioactive particle is in contact with the fluid in the first microfluidic channel, or the radioactive particle is not in contact with the fluid in the first microfluidic channel.

[0074] In some embodiments, the cells include human cells, animal cells, or plant cells; the microorganisms include bacteria, yeast, intestinal microorganisms, soil microorganisms, viruses, microalgae, nematodes, fruit flies, zebrafish larvae. The biological tissues include biological biopsy tissues, organoids, 3D cell cultures; the 3D cell cultures can include at least one of hydrogel-based cell cultures, 3D cell spheres cultured in Matrigel, 3D cell microspheres, and bioprinted 3D cell cultures.

[0075] Thus, the microfluidic chip provided by the embodiments of the present disclosure includes at least one fixing device and at least one microfluidic channel; the at least one fixing device is arranged on the microfluidic chip and used for fixing radioactive particles; the at least one microfluidic channel is arranged on the microfluidic chip and used for culturing at least one of cells, microorganisms, or biological tissues; the distance between each microfluidic channel and the first fixing device is different; the first fixing device is any one of the at least one fixing device; the radiation information of at least one of cells, microorganisms, or biological tissues in the at least one microfluidic channel is used for confirming the influence of the radioactive particles placed in the at least one fixing device on at least one of cells, microorganisms, or biological tissues at different distances from the radioactive particles, so that the radiation influence of the radioactive particles on at least one of cells, microorganisms, or biological tissues at different distances can be accurately evaluated.

[0076] Figure 3 An optional structural schematic diagram of the detection system for evaluating the biological radiation effect of radioactive particles provided by the embodiments of the present disclosure is shown, which will be described according to each part.

[0077] In some embodiments, the system 200 comprises a microfluidic chip 100, a radiation detector 201, and radioactive particles 202.

[0078] The radioactive particles 202 are arranged in the microfluidic chip 100 to emit radiation, and at least one of cells, microorganisms, or biological tissues is placed (cultured) in the microfluidic chip 100. The radiation detector 201 is used to detect the radiation information of at least one of the cells, microorganisms, or biological tissues placed (or cultured) in the microfluidic chip 100 after being irradiated by the radiation.

[0079] The structure of the microfluidic chip 100 is shown in Figure 1 or Figure 2 which will not be repeated here.

[0080] In some embodiments, the system 200 can further comprise a fluid operation device 203 connected to the inlet and / or outlet of at least one microfluidic channel 102 included in the microfluidic chip 100, for at least one of injection, mixing, and collection of fluid, which is used to culture at least one of cells, microorganisms, or biological tissues in the microfluidic channel.

[0081] In some embodiments, the system 200 can further comprise a detection device 204.

[0082] The detection device 204 is used to detect the characteristic information of at least one of cells, microorganisms, or biological tissues in the at least one microfluidic channel 102. Optionally, the detection device can directly detect the liquid in any of the at least one microfluidic channel 102, and / or at least one of cells, microorganisms, or biological tissues cultured in the liquid; the detection device can also detect the liquid collected from the outlet of at least one microfluidic channel 102 included in the microfluidic chip 100 by the fluid operation device 203, and / or at least one of cells, microorganisms, or biological tissues cultured in the liquid. That is, the detection device 204 can directly perform on-chip detection (the liquid, and / or at least one of cells, microorganisms, or biological tissues cultured in the liquid is still in the at least one microfluidic channel 102); or, the detection device 204 can perform off-chip detection (the liquid, and / or at least one of cells, microorganisms, or biological tissues cultured in the liquid is collected by the fluid operation device 203 to other devices outside the microfluidic chip 100).

[0083] In some embodiments, the characteristic information at least includes one of the following: activity information, metabolic information, cell proliferation information, cell number information, pH value information, oxygen distribution information, and apoptosis information.

[0084] In some embodiments, the radioactive particles can include at least one of the following: cobalt-60, palladium-103, iodine-125, strontium-90 / yttrium-90, cesium-137, iridium-192, gold-198, ruthenium-106, californium-252, radium-226, and radon-222. The radioactive particles can also include other particles with radioactive properties, which are not specifically limited in the present disclosure.

[0085] In some embodiments, the radiation detector 201 can include at least one of the following: a silicon photomultiplier (SiPM), a PIN diode array, a silicon pixel detector, a position sensitive avalanche photodiode (PSAPD), a photomultiplier tube (PMT), a charge-coupled device (CCD), a complementary metal-oxide-semiconductor (COMS), and an X-ray detector. The radiation detector can also include other devices with radiation detection capabilities, which are not specifically limited in the present disclosure. The radiation detector 201 is used to detect the radiation intensity and / or radiation energy of the cells, microorganisms, and biological tissues cultured in the microfluidic chip at different distances from the radioactive particles.

[0086] In some embodiments, the liquid in the microfluidic channel can be the supernatant of the culture collected by the at least one microfluidic channel, which is at least one of the following: a supernatant dissolvent, free DNA, RNA, protein, extracellular vesicle, exosome, etc.

[0087] In some embodiments, the cells, microorganisms, and biological tissues are cultured in the microfluidic channel, wherein the cells include at least one of the following: human cells, animal cells, or plant cells (such as human and animal sperm, eggs, and zygotes, etc.); the microorganisms include at least one of the following: bacteria, yeast, intestinal microorganisms, soil microorganisms, viruses, microalgae, nematodes, fruit flies, or zebrafish larvae; the biological tissues include at least one of the following: biological biopsy tissues, organoids, or 3D cell cultures; the 3D cell cultures can include at least one of the following: hydrogel-based cell cultures, 3D cell spheres cultured in Matrigel, 3D cell microspheres, or bioprinted 3D cell cultures.

[0088] In some embodiments, the detection device 204 can include detection probes (such as fluorescent probes, nuclide probes, etc.), which can be directly placed in the at least one microfluidic channel or in the liquid collected by the fluid handling device. The detection device can also include other probes with imaging, sensing, and detection functions, such as electrochemical sensors (point impedance), SPR sensors, radioimaging devices, and optical detection devices, to obtain various physiological indicators of at least one of the cells, microorganisms, or biological tissues in the microfluidic chip under the radiation of the radioactive particles.

[0089] In some optional embodiments, after the detection device 204 performs the corresponding detection operation, the terminal cells can also be subjected to immunofluorescence staining; and the cells in the microfluidic channel can also be collected for subsequent detection such as DNA and RNA sequencing, genome, proteome, radiation metabolome, etc.

[0090] In some possible embodiments, the detection system 200 for evaluating the biological radiation effect of radioactive particles can further comprise a radiation shielding device for shielding the radiation emitted by the radioactive particles.

[0091] Optionally, the fixing device 101 included in the microfluidic chip 100 can be an elliptical groove, which can be fixed on the microfluidic chip in a manner of being embedded or located on the surface of the microfluidic chip, for fixing the radioactive particles. At least one microfluidic channel with a distance different from that between the fixing device can be arranged around the fixing device; the at least one microfluidic channel can be used for culturing the object (at least one of cells, microorganisms or biological tissues) to be detected. The radiation detector can detect the information of the intensity of radiation received by at least one of cells, microorganisms or biological tissues in different microfluidic channels. At least one of cells, microorganisms or biological tissues cultured in the microfluidic chip can be used for in-situ detection (such as detection of the number, activity, apoptosis and metabolism of at least one of cells, microorganisms or biological tissues), supernatant collection detection (such as radiation metabolomics, extracellular free DNA detection, extracellular vesicle detection, etc.) and terminal analysis detection (such as immunohistochemical staining detection, radiation-related expression analysis detection, etc.). That is, through the detection system 200 for evaluating the biological radiation effect of radioactive particles, the radiation received by the detection object such as cells, microorganisms or biological tissues at different distances can be accurately measured, and the biological response of cells to radiation can be accurately and comprehensively detected through various on-chip and off-chip measurement methods. Meanwhile, the microfluidic channels can be independent or interconnected, and can be used for simulating the response of cells and their microenvironment to the radiation of radioactive particles. The establishment of the method and system will have a platform and tool effect, and lay a foundation for evaluating the dose-effect relationship of radioactive particle therapy and developing new methods based on the platform.

[0092] The detection system 200 for evaluating the biological radiation effect of radioactive particles provided by the embodiments of the present disclosure can be used for evaluating the dose-effect relationship of radioactive particles on individuals, and assisting clinicians in specifying an optimal individualized precise diagnosis and treatment scheme of radioactive particles.

[0093] The following describes application embodiments of the detection system 200 for evaluating the biological radiation effect of radioactive particles.

[0094] Figure 4 An optional application schematic diagram of the detection system for evaluating the biological radiation effect of radioactive particles is shown; Figure 5 An application flow schematic diagram of the detection system for evaluating the biological radiation effect of radioactive particles is shown.

[0095] Step S301, at least one of cells, microorganisms or biological tissues is cultured.

[0096] In some embodiments, at least one of cells, microorganisms or biological tissues is cultured in at least one microfluidic channel included in the microfluidic chip before evaluating the radiation performance of the radioactive particles. For example, Figure 4 A side view of the microfluidic chip 100 is shown, at least one of cells, microorganisms or biological tissues is cultured in the microfluidic channel.

[0097] The specific type and quantity of at least one of cells, microorganisms or biological tissues can be set according to actual needs.

[0098] In some embodiments, the cells include at least one of human cells, animal cells or plant cells (such as human and animal sperm, eggs and zygotes, etc.); the microorganisms include at least one of bacteria, yeast, intestinal microorganisms, soil microorganisms, viruses, microalgae, nematodes, fruit flies or zebrafish larvae; the biological tissues include at least one of biological biopsy tissues, organoids or 3D cell cultures; the 3D cell culture can include at least one of hydrogel-based cell culture, 3D cell spheres cultured by Matrigel, 3D cell microspheres or 3D cell culture bioprinted.

[0099] Step S302, the radioactive particles are placed in the fixing device.

[0100] In some embodiments, the radioactive particles are placed in the fixing device included in the microfluidic chip; optionally, one radioactive particle can be placed in the microfluidic chip, or multiple radioactive particles can be placed in the microfluidic chip.

[0101] In another embodiment, in the case of placing one radioactive particle, the radioactive particle can be placed at the center of the microfluidic chip and fixed on the microfluidic chip through the fixing device at the center of the microfluidic chip.

[0102] The radioactive particles emit rays to irradiate at least one of the cells, microorganisms or biological tissues cultured in the microfluidic chip. Figure 4 The radioactive particles emit γ rays, which are only examples, and other rays with radiation properties can also be used.

[0103] Step S303, setting parameters of the radiation detector.

[0104] In some embodiments, the parameters of the radiation detector are set according to actual needs before radiation detection, and the radioactive particles are imaged or analyzed under different control radiation conditions.

[0105] Step S304, the radiation detector detects at least one of the cells, microorganisms or biological tissues in the microfluidic chip.

[0106] In some embodiments, in the case of quantitative detection, the radiation detector obtains the radiation information of at least one of the cells, microorganisms or biological tissues in the microfluidic chip.

[0107] Step S305, the detection device detects at least one of the cells, microorganisms or biological tissues in the microfluidic chip.

[0108] In some embodiments, in the case of quantitative detection, the detection device obtains the biological state and index of at least one of the cells, microorganisms or biological tissues in the microfluidic chip; optionally, the detection device can include an optical detector or an electrochemical detector.

[0109] In other embodiments, in the case of quantitative detection, the extracellular supernatant is collected from the outlet of the at least one microfluidic channel at a corresponding time through the fluid control device, and the extracellular supernatant is quantitatively analyzed by the detection device.

[0110] In some optional embodiments, the microfluidic chip can be placed in the optical, electrochemical, etc. detector, so that the detection device detects at least one of the cells, microorganisms or biological tissues in the microfluidic chip.

[0111] Step S306, based on the detection results of the radiation detector and the detection device, determining the quantitative evaluation information of the dose-effect relationship of the biological sample treated by the radioactive particles.

[0112] In some embodiments, the radiation dose information of at least one of the cells, microorganisms or biological tissues in different microfluidic channels, the biological index measured in situ of the cells, and the biological information in the extracellular supernatant are quantitatively analyzed to determine the quantitative evaluation information of the dose-effect relationship of the biological sample treated by the radioactive particles.

[0113] As shown in Figure 4 , the pulse information collected by the radiation detector is transmitted to the computer; optionally, the detection results obtained by other detection devices are transmitted to the computer, and based on the detection results of the radiation detector and the detection device, the quantitative evaluation information of the dose-effect relationship of the biological sample treated by the radioactive particles is determined.

[0114] The detection system for evaluating the biological radiation effect of radioactive particles is provided in the present disclosure to assist clinicians in formulating precise diagnosis and treatment plans considering the individual biological and physiological differences of radiotherapy, avoiding unnecessary damage and side effects caused by excessive particle implantation, or the problem of incomplete tumor ablation caused by insufficient particle implantation.

[0115] It should be understood that the steps shown above can be reordered, added, or deleted using various forms of flow. For example, the steps described in the present disclosure can be executed in parallel, sequentially, or in a different order, as long as the desired results of the technical solutions disclosed in the present disclosure can be achieved, which is not limited herein.

[0116] The above specific embodiments do not constitute a limitation on the protection scope of the present disclosure. Those skilled in the art should understand that various modifications, combinations, sub-combinations, and substitutions can be made according to design requirements and other factors. Any modifications, equivalent replacements, and improvements made within the spirit and principles of the present disclosure shall be included in the protection scope of the present disclosure.

Claims

1. A microfluidic chip, characterized by, The microfluidic chip comprises at least one fixing device and at least one microfluidic channel; The at least one fixing device is arranged on the microfluidic chip and used for fixing radioactive particles; The at least one microfluidic channel is arranged on the microfluidic chip and used for culturing at least one of cells, microorganisms or biological tissues; the at least one microfluidic channel is in one of a straight line type, a curved type and a zigzag type; the at least one fixing device is arranged outside the at least one microfluidic channel, and the cells, microorganisms or biological tissues cultured in the microfluidic channel do not contact the radioactive particles fixed on the at least one fixing device; an inlet and an outlet are arranged at two ends of each microfluidic channel, respectively; Distances between each microfluidic channel and the first fixing device are different; the first fixing device is any one of the at least one fixing device; Radiation information of at least one of the cells, microorganisms or biological tissues in the at least one microfluidic channel is used for confirming influences of the radioactive particles placed in the at least one fixing device on at least one of the cells, microorganisms or biological tissues at different distances from the radioactive particles.

2. The microfluidic chip according to claim 1, wherein distances between two adjacent microfluidic channels are the same or different.

3. The microfluidic chip according to claim 1 or 2, wherein a communication structure is arranged between two adjacent microfluidic channels; and fluid in at least one microfluidic channel flows into different microfluidic channels through the communication structure.

4. The microfluidic chip according to claim 1, wherein the first fixing device and the at least one microfluidic channel are located on the same horizontal plane; or the first fixing device and the at least one microfluidic channel are located on different horizontal planes.

5. The microfluidic chip according to claim 1, wherein the cells comprise at least one of human cells, animal cells or plant cells; the microorganisms comprise at least one of bacteria, yeasts, intestinal microorganisms, soil microorganisms, viruses, microalgae, nematodes, fruit flies or zebrafish larvae; and the biological tissues comprise at least one of biological biopsy tissues, organoids or three-dimensional (3D) cell cultures. The microfluidic chip, a radiation detector and radioactive particles are provided; The radioactive particles are arranged in the microfluidic chip and used for emitting rays; The microfluidic chip is arranged with at least one of cells, microorganisms or biological tissues; The radiation detector is used for detecting radiation information of at least one of the cells, microorganisms or biological tissues in the microfluidic chip after the at least one of the cells, microorganisms or biological tissues is radiated by the rays; The microfluidic chip comprises at least one fixing device and at least one microfluidic channel; The at least one fixing device is arranged on the microfluidic chip and used for fixing the radioactive particles; ​ ​ 6. A detection system for assessing the biological effects of radiation seeds, characterized by, ​ ​ ​ ​ ​ ​ The at least one microfluidic channel is arranged on the microfluidic chip and used for culturing at least one of cells, microorganisms and biological tissues; the at least one microfluidic channel is one of a straight line type, a curved type and a broken line type; the at least one fixing device is arranged outside the at least one microfluidic channel, and the cells, microorganisms or biological tissues cultured in the microfluidic channel do not directly contact the radioactive particles fixed on the at least one fixing device; the two ends of each microfluidic channel are respectively provided with an inlet and an outlet; The distance between each microfluidic channel and the first fixing device is different; the first fixing device is any one of the at least one fixing device.

7. The system according to claim 6, characterized in that, The first fixing device and the at least one microfluidic channel are located on the same horizontal plane; Alternatively, the first fixing device and the at least one microfluidic channel are located on different horizontal planes.

8. The system of claim 6, wherein, The system further comprises a fluid operation device; The fluid operation device is connected with the inlet and / or outlet of the at least one microfluidic channel included in the microfluidic chip, and is used for at least one of injection, mixing and collection of fluid; The fluid is used for culturing at least one of cells, microorganisms and biological tissues in the microfluidic channel.

9. The system of claim 6, wherein, The system further comprises a detection device; The detection device is used for detecting characteristic information of at least one of cells, microorganisms and biological tissues in the at least one microfluidic channel.

10. The system of claim 9, wherein, The characteristic information at least includes one of the following: activity information, metabolic information, cell proliferation information, cell number information, pH value information, oxygen distribution information and apoptosis information.

Images