Organ-like in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing

Abstract

The invention discloses an organoid in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing. The platform can be widely applied to the fields of regenerative medicine, drug research and development, disease research and the like. According to the platform, in-situ packaging and dynamic culture of the organoid are achieved through an electro-infiltration chip, the morphology and mechanical properties of the organoid are fed back in real time in combination with a holographic microscopy technology, and high-precision hardness gradient control is achieved through a photocuring printing system; after the organoid is formed, the platform can continue to observe the state of the organoid in situ through the digital holographic microscopy system, and specified drugs are conveyed through digital microfluidics. The platform comprises an electro-infiltration chip module, a digital holographic microscopy system, a photocuring biological three-dimensional printing system, a driving control unit and a data analysis processing unit, and supports parallel manufacturing, targeted drug delivery and high-throughput screening of organoids.

Description

Technical Field

[0001] The present invention relates to the field of biomedical engineering, and particularly to an organoid in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing, which is used for parallel manufacturing, targeted drug delivery and high-throughput screening of organoids. Background Art

[0002] Organoids are miniature three-dimensional tissue models constructed by in vitro cell culture techniques, which can simulate the structure and function of real human organs and have broad application prospects in the fields of regenerative medicine, drug screening and disease research. However, traditional organoid manufacturing methods have many deficiencies. For example, it is difficult to achieve high-fidelity morphology and precise regulation of mechanical hardness, and in the process of drug screening, there is a lack of real-time observation and precise control capabilities.

[0003] Although existing bio-three-dimensional printing technologies can achieve automated construction, they still face the following challenges: insufficient mechanical property regulation, traditional methods are difficult to monitor and control the local hardness of organoids in real time, resulting in limited bionic effects; dynamic culture and drug screening are separated, and multiple platforms need to be switched between manufacturing and subsequent drug testing, with low efficiency; weak microenvironment manipulation ability, lack of precise control over culture media and drug delivery, and unable to simulate complex physiological conditions.

[0004] In recent years, digital holographic microscopy (DHM) has received extensive attention in the field of biomedicine. The DHM technology can achieve high-precision imaging and real-time monitoring of microscopic structures, while digital microfluidics (DMF) is based on the principle of electrowetting and manipulates droplet movement through an electric field, achieving precise liquid manipulation and cell culture at the microscale. However, in the existing technology, they have not been deeply integrated with bio-printing and real-time observation technologies to form a closed-loop system.

[0005] In summary, there is currently no system that integrates these three technologies for in-situ manufacturing, dynamic observation and drug screening of organoids. Summary of the Invention

[0006] The present invention discloses an organoid in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing, which is used to solve problems such as the separation of manufacturing and detection, insufficient microenvironment control, and low drug screening efficiency in the existing technology, and realizes the integration of in-situ manufacturing, dynamic observation and drug screening of organoids.

[0007] To achieve the above object, the present invention provides the following solutions:

[0008] The present invention provides an organoid in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing, which is characterized in that it includes an electrowetting chip module, a digital holographic microscopy (DHM) system, a photocuring biological three-dimensional printing system, a drive control unit and a data analysis and processing unit; the electrowetting chip module uses ITO glass as a conductive transparent material, and signal generating devices are connected by wiring on both sides of the chip. A specific electrode layout is designed on the chip, including a printing electrode area for composite material printing, a droplet manipulation electrode area for microfluidic operation of droplets, and a culture electrode area for targeted drug delivery and medium replacement during the culture process. Precise printing of composite materials, droplet manipulation and targeted drug delivery are carried out through electrowetting technology; the digital holographic microscopy (DHM) system reconstructs the three-dimensional model and mechanical hardness characteristics of the organoid in real time through interference patterns, and provides real-time monitoring images as visual feedback during the printing process, microfluidic operation of droplets and culture process; the photocuring biological three-dimensional printing system in-situ prints and encapsulates the composite material with ultraviolet light to form a high-precision organoid; the drive control unit is used to control the electrode drive of the electrowetting chip module, the printing process of the photocuring biological three-dimensional printing system and the image acquisition of the DHM system; the data analysis and processing unit is used to analyze and process the images collected by the DHM system, obtain the morphological and hardness information of the organoid, and is used for the evaluation of drug screening results.

[0009] Preferably, the printing electrode area of the electrowetting chip module is composed of a plurality of microelectrode arrays, the size of each microelectrode is 50-100 μm, and the electrode spacing is 20-50 μm; the droplet manipulation electrode area adopts an interdigitated electrode design, the electrode width is 30-80 μm, and the electrode spacing is 10-30 μm; the electrode distribution in the culture electrode area is optimized according to the requirements of drug delivery and medium replacement.

[0010] Optionally, the digital holographic microscopy (DHM) system includes a strong coherent light source, a beam splitting system and an imaging system; the strong coherent light source generates a plane laser beam through a beam expanding device; the beam splitting system includes a half-wave polarizer, a polarization beam splitter and a beam splitter, which are used to split the laser beam into an object light wave and a reference light wave; the imaging system includes a CCD camera, which is used to collect the hologram formed by the superposition of the object light wave and the reference light wave and reconstruct the three-dimensional morphology and mechanical properties of the organoid.

[0011] Preferably, the photocuring biological three-dimensional printing system includes a digital micromirror and an optical path system; the digital micromirror controls the tilt angle of each micromirror through a computer to adjust the exposure area of ultraviolet light; the optical path system is used to focus the ultraviolet light on the biological material in the microchannel to realize the layer-by-layer curing of the biological material.

[0012] Optionally, the drive control unit includes a signal generator, a printing control circuit, and an image acquisition control circuit; the signal generator is used to generate drive signals for the electro-wetting chip module; the printing control circuit is used to adjust the ultraviolet light intensity and exposure time of the photo-curing biological three-dimensional printing system; the image acquisition control circuit is used to set the image acquisition frequency and trigger timing of the CCD camera.

[0013] Preferably, the data analysis and processing unit uses deep learning algorithms to perform phase unwrapping, image denoising, and feature extraction on the hologram, and evaluates the response of the organoids to the drug through a drug screening model.

[0014] Preferably, the photo-curing biological three-dimensional printing system uses polyethylene glycol diacrylate (PEGDA) as the printing material, with a molecular weight of 700–1000 Da and a photoinitiator concentration of 0.5–2 wt%. Through the closed-loop control of the ultraviolet light intensity (10–50 mW / cm 2 2) and exposure time (50–500 ms), a printing accuracy of less than 50 μm for the organoid structure is achieved.

[0015] Furthermore, the operation method of the organoid in-situ manufacturing, dynamic observation, and drug screening platform includes the following steps: loading a composite material containing cells and biological materials into the electro-wetting chip module, activating the electrodes in the printing electrode area through the drive control unit, and using the photo-curing biological three-dimensional printing system to in-situ print and encapsulate on the chip to form organoids; during the manufacturing and culturing process of the organoids, holographic images are collected in real-time through the DHM system, and the morphological and mechanical parameters of the organoids are analyzed by the data analysis and processing unit; by manipulating the electrodes in the culture electrode area through the drive control unit, different drugs are delivered to the organoids, and combined with the monitoring data of the DHM system and the drug screening model, the drug effects are evaluated and effective drugs are screened.

[0016] The present invention has achieved the following technical effects compared with the prior art:

[0017] The organoid in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing provided by the present invention integrates digital microfluidic electrowetting technology, digital holographic microscopy technology and photocuring biological three-dimensional printing technology into a single platform for the first time, realizing a full-process closed loop of manufacturing-observation-screening, and significantly improving the experimental efficiency; by optimizing the electrode layout and photocuring parameters, the organoid printing accuracy reaches 50 μm, and the drug delivery positioning error is less than 10 μm; the real-time three-dimensional reconstruction and deep learning analysis of the DHM system provide data-driven support for process optimization and drug efficacy evaluation; it can be adapted to a variety of bioinks (such as gelatin, sodium alginate) and cell types (such as tumor organoids, liver organoids), and has universal value in drug R & D and disease model construction. The present invention can solve the problems of separation of manufacturing and detection, insufficient microenvironment control, low drug screening efficiency, etc. in the prior art, and realize the integration of organoid in-situ manufacturing, dynamic observation and drug screening. Description of the Drawings

[0018] The drawings forming a part of this application are used to provide a further understanding of this application, making other features, objects and advantages of this application more obvious. The schematic embodiments of this application and their descriptions are used to explain this application and do not constitute an improper limitation of this application. Obviously, the drawings in the following description are only some embodiments of the present invention, and those of ordinary skill in the art can obtain other drawings based on these drawings without creative efforts. The drawings required for the embodiments will be briefly introduced below. In the drawings:

[0019] Figure 1 FIG. is a schematic diagram of the overall structure of an organoid in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing according to an embodiment of the present application;

[0020] Figure 2 FIG. is a schematic diagram of the application process of an organoid in-situ manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing according to an embodiment of the present application;

[0021] Figure 3 FIG. is a schematic diagram of the digital holographic microscopy system and the photocuring biological three-dimensional printing system in this platform according to an embodiment of the present application;

[0022] In the figure: 1 - Electrowetting chip module; 2 - Digital holographic microscopy system; 21 - Plane mirror; 22 - Microscope objective; 23 - Beam splitter; 24 - Camera; 25 - Stage; 26 - Half-wave plate; 27 - He-Ne laser; 28 - Reference light; 29 - Object light; 210 - Connector; 3 - Photo-curing biological three-dimensional printing system; 31 - Ultraviolet light source; 32 - Digital micromirror device; 4 - Drive control unit; 41 - Image acquisition control circuit; 42 - Signal generator; 43 - Printing control circuit; 5 - Data analysis and processing unit. Specific embodiments

[0023] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0024] The objective of the present invention is to provide an organoid in-situ manufacturing, dynamic observation, and drug screening platform based on digital microfluidics, holographic feedback, and photo-curing printing to solve the problems existing in the aforementioned prior art and achieve the integration of organoid in-situ manufacturing, dynamic observation, and drug screening.

[0025] The present invention provides an organoid in-situ manufacturing, dynamic observation, and drug screening platform based on digital microfluidics, holographic feedback, and photo-curing printing, as Figures 1 to 3 shown, including an electrowetting chip module 1, a digital holographic microscopy system 2, a photo-curing biological three-dimensional printing system 3, a drive control unit 4, and a data analysis and processing unit 5; the digital holographic microscopy system 2 includes a plane mirror 21, a microscope objective 22, a beam splitter 23, a camera 24, a stage 25, a half-wave plate 26, a He-Ne laser 27; a reference light 28, an object light 29, and a connector 210; the photo-curing biological three-dimensional printing system 3 includes an ultraviolet light source 31 and a digital micromirror device 32; the drive control unit 4 includes an image acquisition control circuit 41, a signal generator 42, and a printing control circuit 43. The following will be described in detail in combination with the composition and working process of each module.

[0026] The platform construction of the present invention can be achieved through the following steps:

[0027] S201, Preparation of electrowetting chip.

[0028] Specifically, the electro-wetting chip module 1 uses ITO glass as the substrate material, and three functionalized electrode regions are etched on its surface through a photolithography process: a printing electrode region (size 50 - 100 μm, spacing 20 - 50 μm), a droplet manipulation electrode region (interdigitated electrode design, width 30 - 80 μm, spacing 10 - 30 μm), and a culture electrode region (optimally configured drug delivery path). Both sides of the chip are connected to a signal generator 42 through a flexible cable to receive command signals from the drive control unit 4. In a specific implementation, the electro-wetting chip module 1 precisely manipulates the movement of droplets through the electro-wetting effect to achieve targeted printing of biological materials, replacement of culture medium, and targeted drug delivery.

[0029] S202, Assembly of the DHM system.

[0030] Specifically, the digital holographic microscopy system 2 includes a strong coherent light source (He-Ne laser 27), a beam splitting system, and an imaging system. The beam splitting system consists of a half-wave plate 26 and a beam splitter 28, which is used to split the laser beam into a reference light 28 and an object light 29. The object light 29 irradiates an organoid sample on the stage 25 through a microscope objective 22, and after reflection, it is superimposed with the reference light 28 to form a hologram, which is collected by a CCD camera 24 and transmitted to the data analysis and processing unit 5. The system reconstructs the three-dimensional morphology and mechanical parameters of the organoid in real time through a phase unwrapping algorithm.

[0031] S203, Installation of the photocuring bio-three-dimensional printing system.

[0032] Specifically, the photocuring bio-three-dimensional printing system 3 consists of an ultraviolet light source 31, a digital micromirror 32, and a precision optical path. The digital micromirror 32 adjusts the ultraviolet light exposure pattern by controlling the tilt angle (±12°) of a single micromirror, and the optical path system focuses the ultraviolet light on the printing electrode region of the electro-wetting chip module 1 to achieve layer-by-layer curing of the PEGDA prepolymer (molecular weight 700 - 1000 Da, photoinitiator concentration 0.5 - 2 wt%). During the printing process, the ultraviolet light intensity (10 - 50 mW / cm 2 ) and the exposure time (50 - 500 ms) are closed-loop regulated by a printing control circuit 43 to ensure that the printing accuracy of the organoid structure is ≤50 μm.

[0033] S204, Setting of the drive control unit and the data analysis and processing unit.

[0034] Specifically, the drive control unit 4 includes a signal generator 42, a printing control circuit 43, and an image acquisition control circuit 41. The signal generator 42 generates a drive signal for the electro-wetting chip module 1 (AC voltage 5 - 50V, frequency 1 - 10kHz). The printing control circuit 43 dynamically adjusts the ultraviolet light parameters through the PID algorithm. The image acquisition control circuit 41 sets the acquisition frequency (10 - 30fps) and trigger timing of the CCD camera 24 to ensure synchronous acquisition of holographic images. The data analysis and processing unit 5 is equipped with a deep learning model to denoise, phase-unwrap, and extract features from the holographic images, and outputs the morphological parameters (volume, surface area) and mechanical parameters (Young's modulus) of the organoids. Combining with the drug screening model, it evaluates the response of the organoids to drugs (such as shrinkage rate, cell viability) and generates a drug efficacy score report.

[0035] The in-situ fabrication of organoids according to the present invention can be achieved through the following steps:

[0036] S205, Preparation of composite materials.

[0037] Specifically, a PEGDA prepolymer solution containing cells (such as stem cells, tumor cells) and biomaterials (such as extracellular matrix components) (molecular weight 700 - 1000Da, photoinitiator concentration 0.5 - 2wt%) is prepared and loaded into the printing material storage device of the photocurable bio-three-dimensional printing system 3.

[0038] S206, Setting of printing parameters.

[0039] Specifically, through the printing control circuit 43 of the drive control unit 4, the intensity of the ultraviolet light source 31 (10 - 50mW / cm 2 ) of the photocurable bio-three-dimensional printing system 3, the exposure time (50 - 500ms), and the tilt angle of the digital micromirror 32 (±12°) are set. At the same time, a drive signal for the printing electrode area of the electro-wetting chip module 1 (AC voltage 5 - 50V, frequency 1 - 10kHz) is set through the signal generator 42 to ensure accurate droplet positioning to the target area.

[0040] S207, In-situ printing.

[0041] Specifically, start the photocurable bio-three-dimensional printing system 3. The ultraviolet light emitted by the ultraviolet light source 31 is reflected by the digital micromirror 32 to form a preset pattern and focused on the printing electrode area of the electro-wetting chip module 1 (electrode size 50 - 100μm, pitch 20 - 50μm) to cure the PEGDA prepolymer layer by layer. During the printing process, the digital holographic microscopy system 2 collects holographic images in real time through the microscopic objective lens 22 and the beam splitter 23, and transmits them to the data analysis and processing unit 5 to dynamically optimize the printing parameters.

[0042] The observation process of the present invention can be achieved through the following steps:

[0043] S208, Real-time image acquisition.

[0044] Specifically, during the process of organoid manufacturing and culturing, the image acquisition control circuit 41 of the drive control unit 4 sets the acquisition frequency (10 - 30 fps) of the CCD camera 24, and synchronously obtains the holographic interference pattern of the organoid through the beam splitter 23 and the stage 25. The hologram formed by the superposition of the object light 29 and the reference light 28 is adjusted by the half-wave plate 26 and then analyzed by the data analysis and processing unit 5.

[0045] S209, Image analysis and processing.

[0046] Specifically, the acquired holographic image is transmitted to the data analysis and processing unit 5, and operations such as phase unwrapping, image denoising, and feature extraction are performed using deep learning algorithms to obtain information such as the morphology and hardness of the organoid. By analyzing the image, the growth and change process of the organoid can be monitored in real time, providing data support for subsequent drug screening.

[0047] The drug screening of the present invention can be achieved through the following steps:

[0048] S210, Drug preparation.

[0049] Specifically, different types and concentrations of drugs are dissolved in the culture medium and loaded into the microfluidic liquid storage device of the electro-wetting chip module 1.

[0050] S211, Drug delivery.

[0051] Specifically, the drive control unit 4 activates the culture electrode area (optimally configured electrode spacing 10 - 30 μm), and manipulates the drug-containing droplet to move along a predetermined path (positioning error < 10 μm) to the organoid culture area through the electro-wetting effect.

[0052] S212, Real-time monitoring using the DHM system.

[0053] Specifically, the digital holographic microscopy system 2 captures the drug diffusion process in real time through the stage 25 and the microscope objective 22, and the CCD camera 24 records the deformation response of the organoid (such as the volume shrinkage rate).

[0054] S213, Drug effect evaluation.

[0055] Specifically, after the drug acts for a period of time, the image of the organoid is acquired using the DHM system, and the image is analyzed by the data analysis and processing unit 5 to compare the hardness gradient (change in Young's modulus) and cell activity (fluorescent labeling signal) of the organoid before and after the drug action, and evaluate the effect of the drug.

[0056] S214, Determine the drug effect.

[0057] Specifically, according to indicators such as the morphological changes, hardness changes, and cell viability of the organoids, determine the efficacy and toxicity of the drugs, and screen out effective drugs.

[0058] Through the above implementation manners, an organoid in-situ manufacturing, dynamic observation, and drug screening platform based on digital microfluidics, holographic feedback, and light-curing printing of the present invention can be used for in-situ manufacturing of organoids, dynamic mechanical property regulation, precise control of the culture environment, and high-throughput drug screening.

[0059] For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and without departing from the spirit and basic characteristics of the present invention, the present invention can be implemented in other specific forms. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the present invention. Finally, it should be understood that although this specification is described according to the implementation manners, not every implementation manner only includes an independent technical solution. This narrative manner of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other implementation manners that can be understood by those skilled in the art.

Claims

1. An in situ organoid manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing, characterized in that: It includes an electrowetting chip module, a digital holographic microscope (DHM) system, a photocuring biological 3D printing system, a driving control unit and a data analysis and processing unit; the electrowetting chip module uses ITO glass as a conductive transparent material, and wiring is arranged on both sides of the chip to connect the signal generating device. A specific electrode layout is designed on the chip, including a printing electrode area for printing composite materials, a droplet manipulation electrode area for microfluidic operation of droplets, and a culture electrode area for targeted drug delivery and liquid replacement during the culture process. The electrowetting technology is used to accurately print composite materials, manipulate droplets and deliver targeted drugs; the digital holographic microscope (DHM) system reconstructs the organoid 3D model and mechanical hardness characteristics in real time through interference patterns, and provides real-time monitoring images as visual feedback during the printing process, microfluidic operation of droplets and culture process; the photocuring biological 3D printing system uses ultraviolet light to print and encapsulate the composite materials in situ to form high-precision organoids; The drive control unit is used to control the electrode drive of the electrowetting chip module, the printing process of the photocuring biological 3D printing system, and the image acquisition of the DHM system; the data analysis and processing unit is used to analyze and process the images acquired by the DHM system, obtain the morphology and hardness information of the organoids, and use it for the evaluation of drug screening results.

2. The in situ organoid manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing according to claim 1, characterized in that: The printed electrode area of ​​the electrowetting chip module is composed of multiple microelectrode arrays, each microelectrode has a size of 50-100 μm, and the electrode spacing is 20-50 μm; the droplet manipulation electrode area adopts a staggered electrode design, with an electrode width of 30-80 μm and an electrode spacing of 10-30 μm; the electrode distribution of the culture electrode area is optimized according to the drug delivery and fluid replacement requirements.

3. The in situ organoid fabrication, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing according to claim 1, characterized in that: The digital holographic microscopy (DHM) system includes a strong coherent light source, a spectroscopic system and an imaging system; the strong coherent light source generates a planar laser beam through a beam expansion device; the spectroscopic system includes a half-wave polarizer, a polarization beam splitter and a beam splitter, which are used to split the laser beam into an object light wave and a reference light wave; the imaging system includes a CCD camera, which is used to collect a hologram formed by the superposition of the object light wave and the reference light wave and reconstruct the three-dimensional morphology and mechanical properties of the organoid.

4. The in situ organoid fabrication, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing according to claim 1, characterized in that: The photocuring biological 3D printing system includes a digital micromirror and an optical path system; the digital micromirror controls the tilt angle of each micromirror through a computer to adjust the exposure area of ​​ultraviolet light; the optical path system is used to focus the ultraviolet light on the biological material in the microchannel to achieve layer-by-layer curing of the biological material.

5. The in situ organoid manufacturing, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing according to claim 1, characterized in that: The driving control unit includes a signal generator, a printing control circuit and an image acquisition control circuit; the signal generator is used to generate a driving signal for the electrowetting chip module; the printing control circuit is used to adjust the ultraviolet light intensity and exposure time of the photocuring biological 3D printing system; the image acquisition control circuit is used to set the image acquisition frequency and trigger timing of the CCD camera.

6. The in situ fabrication, dynamic observation and drug screening platform of organoids based on digital microfluidics, holographic feedback and photocuring printing according to claim 1, characterized in that: The data analysis and processing unit uses a deep learning algorithm to perform phase unwrapping, image denoising and feature extraction on the hologram, and evaluates the response of the organoid to the drug through a drug screening model.

7. The in situ organoid fabrication, dynamic observation and drug screening platform based on digital microfluidics, holographic feedback and photocuring printing according to claim 1, characterized in that: The photocurable biological 3D printing system uses polyethylene glycol diacrylate (PEGDA) as the printing material, with a molecular weight of 700-1000Da and a photoinitiator concentration of 0.5-2wt%. The UV light intensity (10-50mW / cm 2 ) and exposure time (50–500ms) to achieve a printing accuracy of less than 50μm for organoid structures.

8. A method for operating the in situ organoid manufacturing, dynamic observation and drug screening platform according to any one of claims 1 to 7, characterized in that: The following steps are involved: A composite material containing cells and biomaterials is loaded into the electrowetting chip module, the electrodes in the printed electrode area are activated by the driving control unit, and the organoids are printed and packaged in situ on the chip using a photocuring biological 3D printing system. During the organoid manufacturing and culture process, holographic images are collected in real time by the DHM system, and the morphological and mechanical parameters of the organoids are analyzed by the data analysis and processing unit. The electrodes in the culture electrode area are manipulated by the driving control unit to deliver different drugs to the organoids, and the monitoring data of the DHM system is combined with the drug screening model to evaluate the drug effects and screen effective drugs.

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