PDMS-based oleogel micro biological robot as well as preparation method and application thereof

Abstract

The invention provides a PDMS (polydimethylsiloxane)-based oleogel miniature biological robot as well as a preparation method and application thereof, and the preparation method comprises the following steps: (1) preparing a biocompatible pCrO2atSiO2 nanorod by adopting a nano coating method; (2) uniformly mixing a PDMS prepolymer, cyclohexane, a PDMS curing agent and BaSO4 particles to obtain a mixed dispersion liquid; adding a pCrO2 coated SiO2 nanorod into the mixed dispersion liquid, ultrasonically mixing uniformly, then heating to react, cooling to room temperature, cleaning and drying to obtain the Si-gel / pCrO2 coated SiO2 oleogel micro-robot. The prepared micro-robot shows high elongation at break and elastic recovery rate, speed self-definition is achieved on the premise of not changing external magnetic field conditions, and the micro-robot shows excellent stability and biocompatibility and enhanced matrix-filler compatibility.

Description

Technical Field

[0001] This invention relates to the field of biorobot technology, and in particular to a PDMS-based oleogel micro-biorobot, its preparation method, and its application. Background Technology

[0002] With the development of electronic information technology and the advancement of non-contact control methods, an increasing number of non-contact soft robots composed of or consisting of non-contact actuators have been developed, focusing on issues such as drive controllability, functional programmability, and environmental adaptability. Currently, a tetherless electrothermal soft robot based on wireless power transfer (WPT) technology has been fabricated. While it effectively addresses environmental interference and insufficient control distance, current non-contact soft robots still face challenges such as insufficient redefinition performance and poor safety, making them difficult to apply in specialized fields such as biomedicine. Developing a microrobot with excellent biocompatibility and redefinable actuation has the potential to become an effective complement to biomedical systems.

[0003] Recently, non-contact ferromagnetic robots capable of remote manipulation within confined lumens have shown promise in biomedical fields such as embolism clearance. For example, a microrobot for stone removal and drug-mediated thrombolysis has been constructed using strontium ferrite droplets; a micro-sensing robot capable of continuously monitoring soft biological tissue properties has been built using neodymium iron boron ferromagnetic powder. However, the actuation rate of these ferromagnetic devices is often uncontrollable or controlled by the strength of an external magnetic field, and continuous and excessively high magnetic field strength can cause irreversible damage to living organisms. To address this issue, the Sitti team proposed a heat-assisted magnetic redefinition method that enables ferromagnetic microrobots to exhibit recoverable custom deformation. Ferromagnetic CrO2 (118°C) with a low Curie temperature and PDMS with a long-term operating temperature exceeding 150°C have become the best choices. However, the significant cytotoxicity of CrO2 and the low modulus and low toughness of PDMS limit their further application as micro-biorobots. Developing a highly biocompatible, reconfigurable, and ultra-flexible microrobot could potentially be an effective complement to current catheter-implantable biomedical devices. Summary of the Invention

[0004] This invention proposes a PDMS-based oleogel micro-biorobot, its preparation method, and its application. The prepared micro-robot exhibits high elongation at break and elastic recovery rate, achieves speed customization without changing external magnetic field conditions, and demonstrates excellent stability, biocompatibility, and enhanced matrix-filler compatibility.

[0005] The technical solution of this invention is achieved as follows: a method for preparing a PDMS-based oleogel microbial robot, comprising the following steps:

[0006] (1) Adopt Biocompatible pCrO2@SiO2 nanorods were prepared by nano-coating method;

[0007] (2) PDMS prepolymer, cyclohexane, PDMS curing agent and BaSO4 particles were mixed to obtain a mixed dispersion; pCrO2@SiO2 nanorods were added to the mixed dispersion, ultrasonically mixed, then heated in a sealed environment, cooled to room temperature, washed and dried to obtain Si-gel / pCrO2@SiO2 oleogel microrobots.

[0008] Furthermore, in step (2), the mass ratio of PDMS prepolymer, cyclohexane, PDMS curing agent and BaSO4 microparticles is 1:5:0.5-0.7:0.1-0.3; the mass ratio of PDMS prepolymer and pCrO2@SiO2 nanorods is 1:0.1-0.6, such as 1:0.1, 1:0.2, 1:0.4, 1:0.6, etc.

[0009] Furthermore, in step (2), the heating reaction conditions are: heating at 110-150℃ for more than 6 hours. The heating temperature can be 110℃, 120℃, 135℃, 140℃, 150℃, etc.

[0010] Further, in step (1), the preparation method of pCrO2@SiO2 nanorods is as follows: 3g of cleaned ferromagnetic pCrO2 powder is dispersed in 320mL of anhydrous ethanol, 80mL of deionized water and 4mL of ammonia (NH3·H2O), and ultrasonically treated to obtain a mixed solution; tetraethyl orthosilicate (TEOS) is rapidly added to the mixed solution, and the mixture is continuously stirred for at least 6h. Finally, the mixture is magnetically absorbed, cleaned and dried to obtain biocompatible pCrO2@SiO2 nanorods.

[0011] Furthermore, the cleaning method for the ferromagnetic pCrO2 powder is as follows: Commercial chromium dioxide (CrO2) is baked and naturally cooled, then placed in a 50 g / L NaHSO3 aqueous solution and placed in a vacuum drying oven at 55-85℃ for at least 16 hours, stirring intermittently, to obtain a CrO2 / NaHSO3 dispersion. The CrO2 / NaHSO3 dispersion is washed multiple times with deionized water, centrifuged after each wash, and the supernatant is removed. The washed CrO2 is dried and crushed to obtain highly thermally conductive ferromagnetic pCrO2 powder. The temperature of the vacuum drying oven can be 55℃, 65℃, 75℃, 85℃, etc.

[0012] Further, in step (2), the cleaning method is as follows: first, clean with cyclohexane solution to remove monomers that have not undergone cross-linking reaction, and then clean with deionized water to remove surface solvent residue.

[0013] PDMS-based oleogel microbial robots prepared using the aforementioned preparation method.

[0014] The PDMS-based oleogel microbiorobot is used as a catheter-implantable biomedical aid, such as a medical robot that can crawl inside the human body for drug delivery and embolism removal.

[0015] The beneficial effects of this invention are:

[0016] This invention is based on the solvothermal reaction method and A flexible micro-Si-gel / pCrO2@SiO2 oleogel microrobot was prepared using a nano-coating method, exhibiting excellent hydrophobicity and hydrophobic stability. The Si-gel matrix prepared by a solvothermal reaction method showed significantly superior flexibility (ultra-low modulus, reaching 54.90 kPa) and toughness (ultra-high elongation at break, reaching 579.70%) compared to the original PDMS, with an increased elongation at break of 174.64%. It also exhibited good elastic recovery, exceeding 90% under 20 cycles of 100% tensile strain and 15 cycles of 80% compressive strain.

[0017] Under cyclic tensile stress of 100% strain and cyclic compression stress of 80% strain, the elastic recovery rate of the microrobot remained stable at over 90%. In the magnetically driven testing system, the microrobot was able to move at a relative speed of 29.5 mm / s. Pre-magnetization of the material at a magnetic field of 60 mT and a temperature of 150 °C increased the relative speed of the microrobot to 70 mm / s under the same experimental conditions, demonstrating that the microrobot can achieve speed customization without changing the external magnetic field conditions. Continuous treatment at 150 °C, repeated magnetization, and 500 consecutive actuations demonstrate the excellent driving stability of the microrobot. The biocompatibility and organic-inorganic phase compatibility of the nano-coated Si-gel / pCrO2@SiO2 were significantly improved. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 Microstructure of pCrO2@SiO2: (a) SEM image of pCrO2, (b) SEM image of pCrO2@SiO2, (c) Structural formation mechanism and TEM image of pCrO2@SiO2;

[0020] Figure 2 (a) Hydrophilicity and hydrophobicity of the original PDMS, PDMS oleogel (Si-gel), and Si-gel / pCrO2@SiO2 oleogel microrobots; (b) Hydrophilicity and hydrophobicity of Si-gel over time.

[0021] Figure 3 A comparison of the elongation at break and elastic modulus of PDMS and Si-gel;

[0022] Figure 4 (a) The elastic recovery rate of Si-gel under cyclic stretching; (b) The elastic recovery rate of Si-gel under cyclic compression.

[0023] Figure 5 Custom drive effect and statistical data of Si-gel / pCrO2@SiO2 microrobot: (a) The microrobot moves along the "ZZU" trajectory under the drive of permanent magnet, (b) The relative displacement-time graph of the microrobot during the movement to the right and left, (c)-(d) The relative displacement-time graph and relative velocity comparison graph of the microrobot before and after pre-magnetization acceleration;

[0024] Figure 6 The driving stability test results of the Si-gel / pCrO2@SiO2 microrobot are as follows: (a) Schematic diagram of the swelling process in PMX-200 solution, (b) Volume change and high temperature resistance during the swelling process, (c) Effect of pre-magnetization and high temperature demagnetization on the relative rate, and (d) Stability under 500 driving cycles.

[0025] Figure 7 Biocompatibility testing of Si-gel / pCrO2@SiO2 microrobots: (a)-(b) fluorescence images of HUVECs cultured on pCrO2 and pCrO2@SiO2 for 5 days, (c) cell viability, (d) CCK-8 statistical results;

[0026] Figure 8 The graph shows the change in interfacial binding energy of the Si-gel / pCrO2@SiO2 microrobot as a function of temperature. Detailed Implementation

[0027] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] A method for preparing a PDMS-based oleogel microbial robot includes the following steps:

[0029] (1) Adopt Biocompatible pCrO2@SiO2 nanorods were prepared by nano-coating method;

[0030] First, the CrO2 was cleaned. 3.5 g of commercial CrO2 was baked in a muffle furnace at 300 °C for 2 hours. After natural cooling, the powder was removed and placed in a 50 g / L NaHSO3 solution. It was then placed in a vacuum drying oven at 65 °C for at least 16 hours, with occasional stirring. The CrO2 / NaHSO3 dispersion was then removed and washed three times with deionized water (centrifuged at 1700 rpm for 2 minutes after each wash and the supernatant was removed). The cleaned CrO2 was placed in a forced-air drying oven at 40 °C for 24 hours to remove all moisture. The resulting powder was then crushed using an agate mortar to obtain highly thermally conductive ferromagnetic pCrO2 powder.

[0031] Then, 3g of the prepared pCrO2 was dispersed in 320mL of anhydrous ethanol, 80mL of deionized water, and 4mL of NH3·H2O, and sonicated for 15min. Next, 1g of TEOS was rapidly added to the mixture, and the mixture was stirred continuously with a stir bar for at least 6h. Finally, the particles in the collection bottle were collected using a samarium cobalt permanent magnet, washed 5 times with deionized water, and dried in a 40℃ forced-air oven for 24h to obtain biocompatible pCrO2@SiO2 nanorods.

[0032] (2) Highly flexible and tough PDMS-based oleogel micro-biorobots were prepared using a solvothermal reaction method.

[0033] First, 3g of vinyl-terminated polydimethylsiloxane (PDMS prepolymer), 15g of cyclohexane, 1.5g of low-hydrogen siloxane (PDMS curing agent), and 0.3g of BaSO4 microparticles were placed in a plastic beaker sealed with aluminum foil and magnetically stirred for 30min. Then, the magnetic stirrer was removed, and 1.2g of pCrO2@SiO2 nanorods were added to the mixed dispersion. The mixture was ultrasonically treated for 20min to ensure uniform dispersion. Next, the dispersion was poured into the lining of a 100mL solvothermal reactor, and the reactor was placed in an oven at 135℃ and heated for 6h.

[0034] After the reactor was allowed to cool naturally to room temperature, the sample was removed and washed five times with cyclohexane solution to remove monomers that had not undergone cross-linking reaction, followed by five washes with deionized water to remove residual solvent from the surface. Natural drying at room temperature yielded the Si-gel / pCrO2@SiO2 oleogel microrobot.

[0035] use The method for coating cleaned pCrO2 is as follows: its microstructure and coating mechanism are as follows. Figure 1 As shown in the figure, SEM results show that the cleaned pCrO2 exhibits a relatively regular rod-shaped nanostructure. After nanocoating, the conductivity of the nanorods deteriorates. This is because the newly formed shell SiO2 has poor conductivity compared to the inner pCrO2 semi-metallic material.

[0036] The hydrophilicity and hydrophobicity test results of the original PDMS, PDMS oleogel (Si-gel), and Si-gel / pCrO2@SiO2 oleogel microrobots are as follows: Figure 2 As shown in (a), the original PDMS prepared by the drying method exhibits a WCA value of 109°, while the WCA value of the Si-gel matrix is ​​significantly increased to 121.5° compared to the original PDMS. The WCA of Si-gel / pCrO2@SiO2 is 116°, a slight decrease compared to pure Si-gel. To demonstrate the hydrophobic stability of the oleogel under long-term operation in a humid environment, the change in hydrophilicity / hydrophobicity of the Si-gel over time was tested (see...). Figure 2 (b) The results show that Si-gel can maintain a hydrophobicity of 114.75° 600 s after a 2 μL droplet is dropped onto the surface (higher than the initial WCA of the original PDMS).

[0037] The elongation at break and elastic modulus values ​​of pristine PDMS prepared by the drying method and Si-gel prepared by the solvothermal method under fracture tensile testing are as follows: Figure 3 As shown, the elongation at break of the original PDMS was 211.09%, while that of the Si-gel increased to 579.70%, representing a 174.64% increase in elongation at break. Furthermore, the elastic modulus of the original PDMS was 610.00 kPa, while that of the Si-gel was 54.90 kPa, a decrease of 91%. The Si-gel oleogel prepared by the solvothermal method exhibited mechanical properties close to those of highly elastic hydrogels, and also displayed stable hydrophobic properties not found in most hydrogel materials.

[0038] The application scenarios of micro-biorobots place high demands on the cyclic mechanical properties of Si-gels. Cyclic tensile and cyclic compression experiments of Si-gels, such as... Figure 4 As shown. The change in elastic recovery rate under cyclic stretching is as follows. Figure 4 As shown in (a), after the first cyclic tensile test at 100% ultimate strain, the elastic recovery rate of the Si-gel was 94.84%. After 20 100% tensile cycles, the elastic recovery rate of the Si-gel was still 91.22%. Furthermore, under 15 cyclic compression tests at 80% ultimate strain, the ultimate stress on the Si-gel ranged from 69.76 ± 0.22 kPa. The variation of the elastic recovery rate under cyclic compression is shown in Figure [figure missing]. Figure 4As shown in (b), after the first 80% compression cycle, the elastic recovery rate of Si-gel was 95.33%. After 15 compression cycles, the elastic recovery rate of Si-gel still exceeded 94%. The above cyclic tensile test at 100% ultimate strain and cyclic compression test at 80% ultimate strain demonstrate that Si-gel exhibits excellent cyclic mechanical properties under ultra-high strain, providing a prerequisite for its application under complex and extreme conditions.

[0039] To verify the customizability of the driving trajectory and further analyze the impact of the pre-magnetization process on the driving performance, the custom driving effect of the Si-gel / pCrO2@SiO2 microrobot was tested, and data statistics on external magnetic field driving were performed. The results are as follows: Figure 5 As shown. By Figure 5 (a) It can be seen that the Si-gel / pCrO2@SiO2 microrobot can move along a "ZZU" trajectory driven by the cylindrical permanent magnet. The relative velocity and final relative displacement of the un-pre-magnetized Si-gel / pCrO2@SiO2 microrobot moving to the right and left are comparable, both achieving a relative displacement of 59 mm within 2 seconds (see...). Figure 5 (b) The results above show that the original Si-gel / pCrO2@SiO2 microrobot can complete movements in different directions with relatively high efficiency and stability. Under a pre-magnetization condition of 60 mT, the microrobot can achieve even more efficient actuation (e.g.,...) without changing the driving magnetic field. Figure 5 (As shown in (c)-(d)). Within 0.5 s after applying an external magnetic field, the unmagnetized and 60 mT pre-magnetized Si-gel / pCrO2@SiO2 microrobots exhibited relative displacements of 1.5 mm and 35 mm, respectively. Throughout the magnetic field actuation process, their average relative velocities were 29.5 mm / s and 70 mm / s, respectively. Pre-magnetization with 60 mT increased the relative velocity by 137.29% while maintaining a constant external magnetic field. For magnetically controlled biorobots, lower magnetic field influence and higher actuation efficiency will demonstrate positive implications.

[0040] The actuation stability of Si-gel / pCrO2@SiO2 microrobots is particularly crucial for their high-precision operation in biological organisms. The actuation stability test results are as follows: Figure 6 As shown in the diagram. A schematic diagram of the swelling of the Si-gel / pCrO2@SiO2 microrobot in PMX-200 silicone oil is shown below. Figure 6 (a). Volume changes of Si-gel / pCrO2@SiO2 microrobots during swelling in PMX-200 and under the influence of high temperature, as shown in... Figure 6As shown in (b), PMX-200 has low viscosity and good flowability, making it easier for it to penetrate into the molecular network of Si-gel, causing Si-gel / pCrO2@SiO2 to swell. Figure 6 (b) It can be seen that the Si-gel / pCrO2@SiO2 microrobot can swell to a basically stable state after standing in PMX-200 silicone oil for 24 hours, and the high temperature of 150℃ will not damage the morphology of the swollen device.

[0041] Besides morphological stability, repeated magnetization and multiple cycles also significantly affect the actuation performance of Si-gel / pCrO2@SiO2 microrobots. Related tests include... Figure 6 As shown in (c)-(d), the relative velocities of the original microrobot and the microrobot pre-magnetized with a 60 mT external magnetic field are 29.5 mm / s and 70.0 mm / s, respectively (see Figure 1). Figure 5 (d) The magnetized device was heated to above the Curie temperature (118°C) and held for 24 hours to disrupt the ordered pCrO2@SiO2 magnetic domains, causing the macroscopic magnetism of the device to disappear. The average relative velocity of the reprogrammed Si-gel / pCrO2@SiO2 microrobot under the same external magnetic field was 29.0 mm / s (moving to the right). In addition, continuous drive tests (e.g., 500 cycles) were performed on the unmagnetized microrobot. Figure 6 (d) As shown in the test results, the average speed of the original Si-gel / pCrO2@SiO2 microrobot is 29.66±1.59 mm / s, with a fluctuation range not exceeding 5.36%. The above test results indicate that the Si-gel / pCrO2@SiO2 microrobot exhibits excellent driving stability under repeated magnetization and multiple continuous driving conditions, which makes its long-term recycling possible.

[0042] To investigate the biocompatibility of Si-gel / pCrO2@SiO2 microrobots, live and dead staining was performed on both pCrO2 and pCrO2@SiO2 samples. Live cells were stained with calcein-AM, and dead cells were stained with acetidine dimer-III / iso-diethylamine-I. The staining results on the sample surfaces at days 1, 3, and 5 of culture are shown below. Figure 7 As shown in (a)-(b). The results show that the cells in the pCrO2 sample disappeared completely by day 5 of culture. However, through... The number of viable cells on the surface of the pCrO2@SiO2 sample coated with this method was significantly increased, and the cell morphology remained a typical "spindle shape". The survival rate of HUVECs cells on the surfaces of both pCrO2 and pCrO2@SiO2 samples was also statistically analyzed. Figure 7 (c) The proliferation behavior of HUVECs cells on the sample surface was determined by the CCK-8 assay (e.g., ...). Figure 7 (d) The absorbance of the pCrO2 surface decreases, indicating that it lacks endothelialization ability. These results demonstrate that pCrO2 exhibits significant cytotoxicity, while pCrO2@SiO2 shows excellent biocompatibility. Improved biocompatibility facilitates the realization of biological functions in Si-gel / pCrO2@SiO2 microrobots, which can be used as catheter-implanted biomedical auxiliary tools, such as medical robots that can crawl within the human body for drug delivery and embolization clearance.

[0043] The interfacial bonding energy (E) of the Si-gel composite system with SiO2 and CrO2 inter The values ​​were 18.32 kcal / mol and 94.04 kcal / mol, respectively. The results indicate that, compared to CrO2, the Si-gel@SiO2 composite system exhibits less repulsion between the two phases, more uniform particle dispersion, and better interfacial stability. To investigate the particle dispersion and interfacial stability of the Si-gel@SiO2 composite system at different temperatures within the reactor, the interfacial binding energy was calculated using the NVT ensemble (isothermal and isovolume) (see...). Figure 8 When the temperature exceeds 90℃, the interfacial binding energy of the system decreases significantly, dropping to 8.54 kcal / mol when the temperature rises to 135℃. The significant reduction in the repulsive force between Si-gel and SiO2 surfaces demonstrates the enhanced particle dispersion and interfacial stability achieved at the high temperature of 135℃ in the reactor.

[0044] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a PDMS-based oleogel microbial robot, characterized in that, Includes the following steps: (1) Adopt Biocompatible pCrO2@SiO2 nanorods were prepared by nano-coating method; (2) PDMS prepolymer, cyclohexane, PDMS curing agent and BaSO4 particles were mixed to obtain a mixed dispersion; pCrO2@SiO2 nanorods were added to the mixed dispersion, ultrasonically mixed, then heated in a sealed environment, cooled to room temperature, washed and dried to obtain Si-gel / pCrO2@SiO2 oleogel microrobots.

2. The preparation method according to claim 1, characterized in that, In step (2), the mass ratio of PDMS prepolymer, cyclohexane, PDMS curing agent and BaSO4 microparticles is 1:5:0.5-0.7:0.1-0.3; the mass ratio of PDMS prepolymer and pCrO2@SiO2 nanorods is 1:0.1-0.

6.

3. The preparation method according to claim 1, characterized in that, In step (2), the heating reaction conditions are: heating at 110-150℃ for more than 6 hours.

4. The preparation method according to claim 1, characterized in that, In step (1), the preparation method of pCrO2@SiO2 nanorods is as follows: 3g of cleaned ferromagnetic pCrO2 powder is dispersed in 320mL of anhydrous ethanol, 80mL of deionized water and 4mL of ammonia water, and ultrasonically treated to obtain a mixed solution; tetraethyl orthosilicate is rapidly added to the mixed solution, and the mixture is stirred continuously for at least 6h. Finally, the mixture is magnetically absorbed, cleaned and dried to obtain biocompatible pCrO2@SiO2 nanorods.

5. The preparation method according to claim 4, characterized in that, The cleaning method for ferromagnetic pCrO2 powder is as follows: After baking and naturally cooling chromium dioxide, it is placed in an aqueous solution of NaHSO3 with a concentration of 50 g / L and placed in a vacuum drying oven at 55-85℃ for no less than 16 h, with occasional stirring during the process, to obtain a CrO2 / NaHSO3 dispersion; the CrO2 / NaHSO3 dispersion is washed multiple times with deionized water, and centrifuged after each wash to remove the supernatant; the washed CrO2 is dried and crushed to obtain ferromagnetic pCrO2 powder with high thermal conductivity.

6. The preparation method according to claim 1, characterized in that, In step (2), the cleaning method is as follows: first, use cyclohexane solution to clean to remove monomers that have not undergone cross-linking reaction, and then use deionized water to clean to remove surface solvent residue.

7. A PDMS-based oleogel microbial robot prepared by the preparation method described in any one of claims 1-6.

8. The application of the PDMS-based oleogel microbiorobot of claim 7 as a catheter implantation biomedical aid.

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