Soft biological micro-robot system and application thereof
By using slender Euglena as soft biological microrobots and controlling their movement with blue light, the problem of manipulating biomimetic soft microrobots in complex environments has been solved, enabling flexible and precise execution of biomedical tasks.
Patent Information
- Application Number
- CN202311724235.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-15
- Publication Date
- 2026-01-16
- Estimated Expiration
- 2043-12-15
AI Technical Summary
Existing biomimetic soft microrobots face challenges in terms of flexibility and precise control during fabrication and actuation, making it difficult to perform tasks in complex environments.
Using slender Euglena as a soft-bodied microrobot, driven by a blue light source, the microrobot's controllable movement, including changes in flagellar oscillation and body deformation, is achieved by controlling the light intensity and duration.
It enables flexible and precise control of soft biological microrobots, allowing them to traverse microfluidic mazes and various confined spaces, thus meeting the needs of biomedical missions.
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Figure CN117798883B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of micro-nano robots, and particularly relates to a soft biological micro-robot system and application thereof. BACKGROUND
[0002] Micro-nano robots are small in size compared with traditional tools, can accurately navigate to biological micro-environments or even areas difficult to reach in the human body for treatment, and thus are highly concerned in the fields of biomedical science and biomedical engineering. Compared with traditional rigid micro-robots, soft micro-robots with deformability and adaptability (changing their own shape to adapt to the environment according to changes in the environment) are particularly promising in performing different tasks in complex environments and winding micro-channels to meet the requirements of biomedical applications. Inspired by soft organisms in nature, researchers have designed various bionic soft micro-robots, such as a magnetic control soft micro-robot prepared by using hydrogel materials inspired by octopus, a light control soft micro-robot prepared by using MXene nanosheet materials inspired by caterpillar, and a light control soft micro-robot prepared by using a new type of polymeric gold nanorod inspired by water strider. However, in order to facilitate preparation and driving, the structure of these bionic soft micro-robots is often greatly simplified, and their performance is greatly compromised. It is still a thorny problem to flexibly and accurately control soft micro-robots. SUMMARY
[0003] The present application aims to provide a soft biological micro-robot system and application thereof, and the soft biological micro-robot system provided by the present application can flexibly and accurately control soft biological micro-robots.
[0004] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions:
[0005] The present application provides a soft biological micro-robot system, comprising a soft biological micro-robot and a blue light source for driving the soft biological micro-robot, wherein the soft biological micro-robot is a slender euglena.
[0006] Preferably, the central wavelength of the blue light source is 440-473 nm.
[0007] Preferably, the illumination intensity of the blue light source is 100-3000 lx.
[0008] Preferably, the system further comprises a simulation motion model, and the simulation motion model comprises a micro-flow maze model or a micro-flow channel model.
[0009] The present application provides the application of the soft biological micro-robot system described in the above technical solutions for non-disease diagnosis or treatment purposes, which comprises: irradiating the soft biological micro-robot by using the blue light source in the soft biological micro-robot system to realize controllable movement of the soft biological micro-robot.
[0010] Preferably, the soft-bodied biological micro-robot satisfies at least one of (a)-(c) during controllable movement:
[0011] (a) the main body of the soft-bodied biological micro-robot does not change in shape and the manner of flagellum swing does not change;
[0012] (b) the main body of the soft-bodied biological micro-robot does not change in shape and the manner of flagellum swing changes;
[0013] (c) the main body of the soft-bodied biological micro-robot changes in shape and the manner of flagellum swing changes.
[0014] Preferably, when the soft-bodied biological micro-robot satisfies (a) during controllable movement, the controllable movement is helical swimming.
[0015] When the helical swimming is performed, the conditions of the irradiation include that the light intensity of the blue light source is 100-200 lx.
[0016] Preferably, when the soft-bodied biological micro-robot satisfies (b) during controllable movement, the controllable movement is polygonal swimming or rotational swimming.
[0017] When the polygonal swimming is performed, the conditions of the irradiation include that the light intensity of the blue light source is 1000-1500 lx, the irradiation is intermittent, the duration of each irradiation is 200-1200 ms, and the time of each stop of irradiation is 100-200 ms.
[0018] When the rotational swimming is performed, the conditions of the irradiation include that the light intensity of the blue light source is 2900-3000 lx, the irradiation is intermittent, the duration of each irradiation is 20α / 3 ms, the α is the rotation angle of the soft-bodied biological micro-robot during each irradiation, and the time of each stop of irradiation is 100-1200 ms.
[0019] Preferably, when the soft-bodied biological micro-robot satisfies (c) during controllable movement, the controllable movement is controllable deformation movement. When the controllable deformation movement is performed, the conditions of the irradiation include that the light intensity of the blue light source is 2900-3000 lx, the irradiation is continuous, and the time of continuous irradiation is 3-20 s.
[0020] The application provides a soft biological micro-robot system, comprising a soft biological micro-robot and a blue light source for driving the soft biological micro-robot, wherein the soft biological micro-robot is a Euglena gracilis. BRIEF DESCRIPTION OF DRAWINGS
[0021] Figure 1 Figure 1 is a morphological diagram of the soft biological micro-robot in Example 1;
[0022] Figure 2 Figure 2 is a diagram of the change in the moving direction of the soft biological micro-robot in Example 1 under the action of the blue light source;
[0023] Figure 3 Figure 3 is a diagram of the deformation of the soft biological micro-robot in Example 1 under the action of the blue light source. DETAILED DESCRIPTION
[0024] The application provides a soft biological micro-robot system, comprising a soft biological micro-robot and a blue light source for driving the soft biological micro-robot, wherein the soft biological micro-robot is a Euglena gracilis.
[0025] The soft biological micro-robot system provided by the application comprises a soft biological micro-robot, and the soft biological micro-robot is a Euglena gracilis. In the application, the length (l) of the Euglena gracilis is preferably 40-50 μm, the width (w) is preferably 9-10 μm, and the Euglena gracilis belongs to the category of Euglenozoa, Euglenida, Euglenida, Euglenidae and Euglena. In the application, the Euglena gracilis mother liquor is centrifuged, and the obtained Euglena gracilis is resuspended in pure water to prepare a soft biological micro-robot solution for standby. In the application, the rotation speed of the centrifugation is preferably 1200-1800 rpm, more preferably 1500 rpm; the time is preferably 5-15 min, more preferably 10 min. In the application, the concentration of the soft biological micro-robot solution is preferably 1.5×10 2 -2.5×10 2 0 / mL, more preferably 2.0×10 2In an embodiment of the present application, the E. gracilis mother liquor is purchased from Wuhan Branch of the Chinese Academy of Sciences Freshwater Algae Culture Collection Center. In an embodiment of the present application, the soft-bodied micro-robot solution is dropped on a glass slide, and then placed on the observation platform of a research-grade inverted microscope, and a blue light source is used to drive the soft-bodied micro-robot, so as to facilitate observation of the movement of the soft-bodied micro-robot.
[0026] The soft-bodied micro-robot system provided by the present application comprises a blue light source for driving the soft-bodied micro-robot. In the present application, the central wavelength of the blue light source is preferably 440-473 nm, and more preferably 450 nm. In the present application, the illumination intensity of the blue light source is preferably 100-3000 lx, and can be 100-200 lx, 1000-1500 lx or 2900-3000 lx. The present application preferably uses a blue light-emitting diode as the blue light source.
[0027] As an embodiment of the present application, the soft-bodied micro-robot system comprises a simulation movement model, and the simulation movement model comprises a microfluidic maze model or a microfluidic channel model, and the microfluidic channel model comprises a 2D microfluidic channel, a 3D microfluidic channel or a curved microfluidic channel. The soft-bodied micro-robot in the present application can not only accurately pass through the microfluidic maze under the irradiation of the blue light source, but also pass through different restricted spaces, such as 2D microfluidic channels, 3D microfluidic channels and curved microfluidic channels. In an embodiment of the present application, the width of the 2D microfluidic channel is 5 μm, and the length is 100 μm; the width of the 3D microfluidic channel is 5 μm, the length is 100 μm, and the depth is 7 μm; and the width of the curved microfluidic channel is 3 μm.
[0028] The movement of Euglena gracilis is random without external light source irradiation, and the soft-bodied biological micro-robot system provided by the application can realize controllable movement (including movement under deformation or non-deformation) of the soft-bodied biological micro-robot through a blue light source, which is closely related to the eyespot, photoreceptor and flagellum of Euglena gracilis. The eyespot acts as a light shielding device, the photoreceptor can absorb light energy and transmit it to the flagellum to change the jumping of the flagellum, and finally cause the movement mode of the soft-bodied biological micro-robot to change. In this regard, Euglena gracilis becomes a soft-bodied biological micro-robot whose movement can be controlled by light. Especially under the irradiation of high-intensity light (such as light intensity of 3000 lx), the movement direction and deformation degree of the soft-bodied biological micro-robot can be controlled by controlling the irradiation time. As shown in the results of the examples of the application, under the condition of light intensity of 3000 lx, when the irradiation time is 400 ms, the rotation angle of the soft-bodied biological micro-robot is 60°, and when the irradiation time increases to 800 ms, 1200 ms, 1600 ms, 2000 ms and 2400 ms, the rotation angle increases to 120°, 180°, 240°, 300° and 360°, respectively. With the continuous increase of the irradiation time, when the irradiation time is 3 s, the main body of the soft-bodied biological micro-robot begins to deform slightly, and the deformation rate is about 15%, when the irradiation time is 5 s, the shape of the main body of the soft-bodied biological micro-robot changes from spindle to spherical, and the deformation rate reaches 100%, and when the irradiation time is 8 s, the shape of the soft-bodied biological micro-robot returns to the original spindle shape, which shows that the soft-bodied biological micro-robot can undergo periodic deformation under high-intensity light irradiation. The soft-bodied biological micro-robot system provided by the application has a simple structure, and can realize flexible and accurate control of the soft-bodied biological micro-robot through only a blue light source. Moreover, the soft-bodied biological micro-robot has high biocompatibility and biodegradability, which lays a foundation for subsequent execution of various complex biomedical tasks.
[0029] The application provides an application of the soft-bodied biological micro-robot system in non-disease diagnosis or treatment, which comprises: irradiating the soft-bodied biological micro-robot by using the blue light source in the soft-bodied biological micro-robot system to realize controllable movement of the soft-bodied biological micro-robot.
[0030] In the application, the soft-bodied biological micro-robot preferably meets at least one requirement in (a)-(c) during controllable movement:
[0031] (a) the main body of the soft-bodied biological micro-robot does not deform and the swinging mode of the flagellum does not change;
[0032] (b) the main body of the soft-bodied biological micro-robot does not deform and the swinging mode of the flagellum changes;
[0033] (c) the main body of the soft-bodied biological microrobot is deformed and the manner of flagella swing is changed.
[0034] In the present application, the main body of the soft-bodied biological microrobot refers to the part other than the flagella.
[0035] In the present application, when the soft-bodied biological microrobot meets the requirement of (a) during controllable movement, the controllable movement is preferably helical swimming; when the helical swimming is performed, the conditions of the irradiation include: the light intensity of the blue light source is preferably 100-200 lx, more preferably 100-150 lx; the irradiation mode and time of the blue light source are not particularly limited.
[0036] In the present application, when the soft-bodied biological microrobot meets the requirement of (b) during controllable movement, the controllable movement is preferably polygonal swimming or rotational swimming. In the present application, when the polygonal swimming is performed, the conditions of the irradiation include: the light intensity of the blue light source is preferably 1000-1500 lx, more preferably 1000-1200 lx; the irradiation mode is preferably intermittent irradiation, the duration of each irradiation is preferably 200-1200 ms, more preferably 400-800 ms, and the time of each stop irradiation is preferably 100-200 ms, more preferably 100-150 ms. In the present application, when the rotational swimming is performed, the conditions of the irradiation include: the light intensity of the blue light source is preferably 2900-3000 lx, more preferably 2950-3000 lx; the irradiation mode is intermittent irradiation, the duration of each irradiation is preferably 20α / 3 ms, wherein α is the rotation angle of the soft-bodied biological microrobot during each irradiation (for example, when the rotation angles of the soft-bodied biological microrobot are required to be 60°, 120°, 180°, 240°, 300° and 360°, respectively, the irradiation times are 400 ms, 800 ms, 1200 ms, 1600 ms, 2000 ms and 2400 ms, respectively), and the time of each stop irradiation is preferably 100-1200 ms, more preferably 200-500 ms.
[0037] In the present application, when the soft-bodied biological microrobot meets the requirement of (c) during controllable movement, the controllable movement is preferably controllable deformation movement; when the controllable deformation movement is performed, the conditions of the irradiation include: the light intensity of the blue light source is preferably 2900-3000 lx, more preferably 2950-3000 lx; the irradiation mode is preferably continuous irradiation, and the time of the continuous irradiation is preferably ≥3 s, more preferably 3-450 s, more preferably 5-200 s. In the present application, the controllable deformation movement is preferably linear controllable deformation movement and / or curved controllable deformation movement.
[0038] The technical solutions in the present application will be clearly and completely described below in combination with the embodiments in the present application. Apparently, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all the other embodiments obtained by those skilled in the art without creative work fall within the scope of the present application.
[0039] The preparation method of the microfluidic labyrinths used in the following examples is as follows:
[0040] According to the design drawings provided by Jiangsu Dexi Fluid Co., Ltd., China, the microfluidic labyrinth model was drawn by AutoCAD software; the polydimethylsiloxane (PDMS, Shenzhen Xiaohuo Biological Technology Co., Ltd., Dow Corning) was placed in a vacuum pump to remove bubbles, the PDMS without bubbles was introduced into the microfluidic labyrinth model, and the PDMS was cured by heating at 70℃ for 3h in a microwave oven, then the cured PDMS was peeled off from the microfluidic labyrinth model and tightly attached to a glass slide to prepare a microfluidic labyrinth.
[0041] The restricted spaces used in the following examples are 2D microfluidic channels (width of 5μm, length of 100μm), 3D microfluidic channels (width of 5μm, length of 100μm, depth of 7μm) and curved microfluidic channels (width of 3μm), and the preparation method is as follows:
[0042] According to the design drawings provided by Jiangsu Dexi Fluid Co., Ltd., China, the 2D microfluidic channel model, 3D microfluidic channel model and curved microfluidic channel model were drawn by AutoCAD software; the polydimethylsiloxane (PDMS, Shenzhen Xiaohuo Biological Technology Co., Ltd., Dow Corning) was placed in a vacuum pump to remove bubbles, the PDMS without bubbles was introduced into the 2D microfluidic channel model, 3D microfluidic channel model and curved microfluidic channel model respectively, and the PDMS was cured by heating at 70℃ for 3h in a microwave oven, then the cured PDMS was peeled off from the 2D microfluidic channel model, 3D microfluidic channel model and curved microfluidic channel model respectively and tightly attached to a glass slide to prepare different restricted spaces.
[0043] Example 1
[0044] The E. gracilis mother liquor was purchased from Wuhan Freshwater Algae Culture Collection Center of the Chinese Academy of Sciences, and the E. gracilis mother liquor was centrifuged at a speed of 1500rpm for 10min in a centrifuge, and the obtained E. gracilis was resuspended in 1mL of pure water to prepare a solution with a concentration of 2.0×10 2Example 1: The solution of soft biological micro-robot was prepared by mixing 100 μL of the solution of soft biological micro-robot with a concentration of 1.0×106 / mL with 100 μL of the solution of soft biological micro-robot with a concentration of 1.0×106 / mL, and then 100 μL of the solution of soft biological micro-robot was dropped on the glass slide by using a pipette, and then placed on the observation platform of the research-grade inverted microscope, and a blue light source with a central wavelength of 450 nm was used as the blue light source, and the motion direction and deformation of the soft biological micro-robot were controlled by changing the light intensity and illumination time.
[0045] Figure 1 Figure 1 is a morphological diagram of the soft biological micro-robot in Example 1, in which the left side is a bright field image and the right side is a corresponding fluorescent image, and the soft biological micro-robot is a naked Chlorella sp. Figure 1 It can be seen that the morphology of the soft biological micro-robot is a slender naked Chlorella sp., with a length of 40-50 μm and a width of 9-10 μm.
[0046] Figure 2 Figure 2 is a diagram showing the change in the motion direction of the soft biological micro-robot in Example 1 under the action of the blue light source, and the following will be combined with Figure 2 The motion direction of the soft biological micro-robot in this example will be described in detail. As shown in a of Figure 2 for low-intensity light irradiation (light intensity of 100 lx), the light stimulation is small, so the flagella of the soft biological micro-robot are always in the "figure-eight shape" (i.e., the waving mode of the flagella does not change), and under this condition, the motion mode of the soft biological micro-robot is spiral swimming in a natural state; as shown in b of Figure 2 for medium-intensity light irradiation (light intensity of 1000 lx), when the soft biological micro-robot perceives the light stimulation through the photoreceptor, the flagella will change from the "figure-eight shape" to the "noose shape", and then from the "noose shape" to the "figure-eight shape" (i.e., the waving mode of the flagella changes), and this process will be repeated periodically, and under this condition, the motion mode of the soft biological micro-robot is polygonal swimming; as shown in c of Figure 2 for high-intensity light irradiation (light intensity of 3000 lx), the photoreceptor of the soft biological micro-robot is always stimulated by light, and the flagella are always maintained in the "noose shape" (i.e., the waving mode of the flagella changes), and under this condition, the motion mode of the soft biological micro-robot is rotational swimming in place, and when the light source is turned off, the soft biological micro-robot returns to spiral swimming in a natural state, so the motion direction of the soft biological micro-robot can be controlled by changing the illumination time of the high-intensity light. As shown in d of Figure 2 under the condition of light intensity of 3000 lx, when the illumination time is 400 ms, the rotation angle of the soft biological micro-robot is 60° based on the horizontal direction, and when the illumination time is increased to 800 ms, 1200 ms, 1600 ms, 2000 ms and 2400 ms, the rotation angle is increased to 120°, 180°, 240°, 300° and 360°, respectively, and according to the linear fitting of the above results, the result is as follows:Figure 2 As shown in figure e, under high-intensity light irradiation, the rotation angle of the soft biological microrobot increases linearly with increasing illumination time. Based on the above results, this embodiment uses a syringe to deliver a concentration of 2.0 × 10⁻⁶... 2 A solution of soft biological microrobots at a concentration of 100 cells / mL was injected into a microfluidic maze. The microrobots were then placed on the observation platform of a research-grade inverted microscope. A blue LED with a center wavelength of 450 nm and an illumination intensity of 3000 lx was used to illuminate the soft biological microrobots. By controlling the illumination time, the soft biological microrobots were successfully controlled to navigate the microfluidic maze (e.g., ...). Figure 2 As shown in f), soft biological microrobots can get lost in microfluidic mazes in the absence of light (as shown in f). Figure 2 (as shown in g).
[0047] Figure 3 The image below shows the deformation of the soft biological microrobot in Example 1 under the action of a blue light source. Figure 3 The deformation of the soft biological microrobot described in this embodiment is explained in detail. The deformation of the soft biological microrobot in this embodiment is mainly caused by flagellar dysfunction. In this embodiment, the deformation rate is used to characterize the degree of deformation of the soft biological microrobot (here, deformation refers to the deformation of the main body of the soft biological microrobot). The deformation rate is calculated according to the following formula: D = l / w × 100%, where D represents the deformation rate, l represents the length of the soft biological microrobot, and w represents the width of the soft biological microrobot. Figure 3 As shown in Figure a, under conditions of no light (control group) and light intensities of 100 lx, 1000 lx, and 3000 lx, the soft bio-microrobot only began to deform after continuous irradiation for at least 3 seconds under high-intensity light (3000 lx). Specifically, continuous irradiation with high-intensity light (3000 lx) causes irregular flagellar waving, i.e., flagellar dysfunction. Under this condition, the soft bio-microrobot exhibits deformations such as bending, stretching, and contraction. Therefore, subsequent experiments were conducted under a light intensity of 3000 lx. Figure 3 As shown in b, when the illumination duration is 3s, the soft biological microrobot begins to deform slightly, with a deformation rate of approximately 15%; when the illumination duration is 5s, the shape of the soft biological microrobot changes from a spindle shape to a sphere, with a deformation rate reaching 100%; notably, when the illumination duration is 8s, the shape of the soft biological microrobot returns to its original spindle shape, indicating that the soft biological microrobot can undergo periodic deformation under high-intensity light irradiation conditions. Figure 3As shown in c of FIG. 1, when the illumination time is 0s, the position of the soft-bodied micro-robot is the initial position, and as the illumination time is prolonged, the soft-bodied micro-robot deforms and moves forward, which shows that in the unconstrained space, the soft-bodied micro-robot can deform and move forward to realize the linear controllable deformation movement under the high-intensity light irradiation. Based on the above results, in this embodiment, the soft-bodied micro-robot solution with a concentration of 2.0×10 2 The soft-bodied micro-robot solution with a concentration of 2.0×10 Figure 3 As shown in d of FIG. 1, the soft-bodied micro-robot solution with a concentration of 2.0×10 Figure 3 As shown in e of FIG. 1, the soft-bodied micro-robot solution with a concentration of 2.0×10 Figure 3 As shown in f of FIG. 1, the soft-bodied micro-robot solution with a concentration of 2.0×10
[0048] The above only describes the preferred embodiments of the present application, and it should be noted that for those skilled in the art, some improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.
Claims
1. Application of a soft-bodied biological micro-robot system for non-disease diagnosis or treatment purposes, the soft-bodied biological micro-robot system comprising a soft-bodied biological micro-robot and a blue light source for driving the soft-bodied biological micro-robot, the soft-bodied biological micro-robot being a slender euglena; The application comprises: the soft-bodied biological micro-robot is irradiated by the blue light source in the soft-bodied biological micro-robot system to realize controllable movement of the soft-bodied biological micro-robot; the soft-bodied biological micro-robot meets the following requirements during controllable movement: (a) the main body of the soft-bodied biological micro-robot does not deform and the swing mode of the flagellum does not change; when the soft-bodied biological micro-robot meets the requirement (a) during controllable movement, the controllable movement is spiral swimming; when the spiral swimming is performed, the irradiation conditions include: the light intensity of the blue light source is 100-200 lx; (b) the main body of the soft-bodied biological micro-robot does not deform and the swing mode of the flagellum changes; when the soft-bodied biological micro-robot meets the requirement (b) during controllable movement, the controllable movement is polygonal swimming or rotational swimming; when the polygonal swimming is performed, the irradiation conditions include: the light intensity of the blue light source is 1000-1500 lx, the irradiation mode is intermittent irradiation, the duration of each irradiation is 200-1200 ms, and the stopping time of each irradiation is 100-200 ms; when the rotational swimming is performed, the irradiation conditions include: the light intensity of the blue light source is 2900-3000 lx, the irradiation mode is intermittent irradiation, the duration of each irradiation is 20α / 3 ms, the α is the rotation angle of the soft-bodied biological micro-robot during each irradiation, and the stopping time of each irradiation is 100-1200 ms; (c) the main body of the soft-bodied biological micro-robot deforms and the swing mode of the flagellum changes; when the soft-bodied biological micro-robot meets the requirement (c) during controllable movement, the controllable movement is controllable deformation movement; when the controllable deformation movement is performed, the irradiation conditions include: the light intensity of the blue light source is 2900-3000 lx, the irradiation mode is continuous irradiation, and the duration of continuous irradiation is ≥ 3 s.
2. Use according to claim 1, characterized in that, The central wavelength of the blue light source is 440-473 nm.
3. Use according to claim 1, characterized in that, Further comprising a simulation movement model, the simulation movement model comprising a micro-flow maze model or a micro-flow channel model.
4. Use according to claim 1, characterized in that, The duration of continuous irradiation in the (c) is 3-450 s.