U.S. patent application number 16/362834 was filed with the patent office on 2019-11-21 for 3d bio-printer.
This patent application is currently assigned to Taiyuan University of Technology. The applicant listed for this patent is Taiyuan University of Technology. Invention is credited to Xing GUO, Aoqun JIAN, Shengbo SANG, Zhongyun YUAN, Hulin ZHANG, Wendong ZHANG, Kai ZHUO.
Application Number | 20190351666 16/362834 |
Document ID | / |
Family ID | 68534101 |
Filed Date | 2019-11-21 |
United States Patent
Application |
20190351666 |
Kind Code |
A1 |
SANG; Shengbo ; et
al. |
November 21, 2019 |
3D BIO-PRINTER
Abstract
A 3D bio-printer capable of detecting cell activity is provided.
The 3D bio-printer includes an upper PC and a lower 3D printer. A
conveying hose is connected to a printhead base of the printer, and
a temperature controller is connected to the conveying hose. A
printhead controller is connected to the other end of the conveying
hose, a printhead is connected to the bottom of the printhead
controller, and a main control cabinet controls the printhead to
work via a signal generator. A prototyping table is provided under
the printhead and is connected with a cell activity detecting
device for detecting activity of a printed product. Cell activity
can be detected in the process of printing, which ensures that the
printed biological tissues maintain biological activity. It can
supply multi-biological raw materials and realize multi-biological
material printing, which ensures an environment suitable for
biological material printing.
Inventors: |
SANG; Shengbo; (Taiyuan Shi,
CN) ; YUAN; Zhongyun; (Taiyuan Shi, CN) ;
ZHANG; Hulin; (Taiyuan Shi, CN) ; JIAN; Aoqun;
(Taiyuan Shi, CN) ; ZHUO; Kai; (Taiyuan Shi,
CN) ; GUO; Xing; (Taiyuan Shi, CN) ; ZHANG;
Wendong; (Taiyuan Shi, CN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Taiyuan University of Technology |
Taiyuan Shi |
|
CN |
|
|
Assignee: |
Taiyuan University of
Technology
Taiyuan Shi
CN
|
Family ID: |
68534101 |
Appl. No.: |
16/362834 |
Filed: |
March 25, 2019 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C12M 41/48 20130101;
B33Y 40/00 20141201; B29C 64/209 20170801; B29C 64/295 20170801;
B33Y 50/02 20141201; B33Y 30/00 20141201; B29C 64/393 20170801;
C12N 5/0062 20130101; C12M 33/00 20130101 |
International
Class: |
B33Y 30/00 20060101
B33Y030/00; C12N 5/00 20060101 C12N005/00; B33Y 40/00 20060101
B33Y040/00 |
Foreign Application Data
Date |
Code |
Application Number |
May 10, 2018 |
CN |
201810444116.2 |
May 11, 2018 |
CN |
201810449399.X |
Claims
1. A 3D bio-printer capable of detecting cell activity, comprising:
an upper PC; and a lower 3D printer, wherein: the lower 3D printer
includes: a main control cabinet; a stepping motor; a signal
generator; a mechanical arm; a printhead base; a printhead; a
printhead controller; a prototyping table; an air pump; an air pump
control box; and an air tank, the upper PC is connected with the
main control cabinet; the main control cabinet controls motion of
the mechanical arm by the stepping motor; the mechanical arm is
connected to the printhead base; the printhead base is connected
with a conveying hose which is used for storing and conveying
biological raw materials; a first end of the conveying hose is
connected with the air pump, the air pump control box and the air
tank through a conduit, and controls by the air pump speed of
material feeding; a temperature controller is connected to the
conveying hose; a second end of the conveying hose is connected to
the printhead controller; the printhead controller is internally
designed with a selector circuit and can select a working printhead
channel according to requirements; the main control cabinet is
connected to a power clock end of the signal generator; an output
end of the signal generator is connected to the printhead
controller as a work triggering signal of the printhead controller;
the prototyping table is provided under the printhead and is
connected with a cell activity detecting device for detecting cell
activity of a printed product; the cell activity detecting device
includes a mechanical transport arm, an operation table, a reagent
kit, and a detector; the mechanical transport arm is connected with
the operation table, a circular lifting platform is provided in the
center of the operation table, and the reagent kit and the detector
are fixed on the operation table; and the detector is connected
with the upper PC through a signal line.
2. (canceled)
3. The 3D bio-printer according to claim 1, wherein the conveying
hose and corresponding printhead includes respectively five hoses
and five printheads, and switches of printing channels are selected
according to printing requirements.
4. The 3D bio-printer according to claim 1, wherein the printhead
is a detachable printhead and have its temperature sensed in real
time.
5. The 3D bio-printer according to claim 1, wherein after a
detection at a cell activity detection table, it is determined
whether configuration of the 3D printer is appropriate according to
whether the cell activity is good or not, and when the
configuration is inappropriate, cause of the inappropriateness is
determined and is fed back to the printhead controller for a
real-time adjustment to ensure good cell activity.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This patent application claims the benefit of Chinese Patent
Application No. 201810449399.X, filed May 11, 2018, and Chinese
Patent Application No. 201810444116.2, filed May 10, 2018, contents
of which are incorporated by reference herein.
BACKGROUND
1. Technical Field
[0002] The present disclosure relates to the technical field of
biological tissue engineering, and more particularly, to a 3D
bio-printer capable of detecting cell activity.
2. Introduction
[0003] 3D printing is a type of rapid prototyping technology. It is
a technique of constructing an object by layer-by-layer-printing
based on digital model files and using powdered metal or
plasticizable adhesive materials. Tissue engineering incorporates
subjects such as engineering, life science, and material science.
By simulating the process of human tissue and organ formation,
structures having biological activity can be constructed and
cultured in vitro. Among them, 3D printing technology has become
the most powerful research means in the tissue engineering field
because it can mold any complicated three-dimensional structure
using a variety of materials. The principle of 3D printing
technology is layered manufacturing, accumulated layer by layer. A
conventional cell printhead mixes cells with biological materials
and extrudes the mixture to form a silk-like shape, then
reciprocates repeatedly to form a plane, and forms a corresponding
three-dimensional structure as the planes accumulate. It is a means
capable of positioning and assembling biomaterials or cell units,
manufacturing medical devices, tissue engineering scaffolds,
tissues and organs and the like according to the principle of
material manufacturing driven by digital 3D modelling.
[0004] However, 3D bio-printing is still very different from the
conventional 3D printing technology in that, in addition to the use
of core technology of the conventional 3D printing, all
manufacturing processes of 3D bio-printing must conform to
biological standards to ensure cell activity and tissue functions,
as well as conforming to medical standards, such as sterility. At
present, there are many technical defects in 3D bio-printing
devices, for example: (1) the cell printing speed is slow; (2) the
cell printing precision is low; (3) it is difficult to detect the
cell activity of printed tissues and organs in real time; (4) it is
difficult to realize automation in the process of 3D bio-printing;
(5) the number and type of printhead are limited, and replacement
of the printheads is complicated; and (5) it is not possible to
adjust printer configuration in real time according to cell
activity during printing to increase printing success rate.
SUMMARY
[0005] The present disclosure overcomes the deficiencies in prior
art. An object of the present disclosure is to provide a 3D
bio-printer capable of detecting cell activity so as to overcome
the problems of low printing precision, inability to ensure the
activity of printed tissue cells, frequent replacement of
printheads, etc.
[0006] In order to achieve the aforementioned object, the present
disclosure adopts the following technical solutions: a 3D
bio-printer capable of detecting cell activity comprises an upper
personal computer (PC) and a lower 3D printer. The lower 3D printer
includes a main control cabinet, a stepping motor, a signal
generator, a mechanical arm, a printhead base, a printhead, a
printhead controller, a prototyping table, a cell activity
detection table, an air pump, an air pump control box, and an air
tank.
[0007] The upper PC may be connected with the main control cabinet
by wire or wirelessly. The main control cabinet controls the motion
of the mechanical arm by the stepping motor, and the mechanical arm
is connected to the printhead base. The printhead base is connected
with a material conveying hose which is used for storing and
conveying biological raw materials. A top end of the material
conveying hose is connected with the air pump, the air pump control
box and the air tank through a conduit, and precisely controls the
speed of material feeding by a precise control of the air pressure
of the air pump. A temperature controller and a temperature sensor
are connected to the material conveying hose. The temperature of
the material conveying hose is monitored in real time by the
temperature sensor. The temperature is adjusted in time by the
temperature controller to keep a suitable temperature and create a
good feeding environment. The other end of the material conveying
hose is connected to the printhead controller, and the printhead is
connected to the lower end of the printhead controller. The
discharge hole of the printhead can automatically adjust the
opening size of the printhead nozzle hole according to requirements
on the discharge speed. The feeding speed is precisely controlled
by adjusting the air pressure of the air pump and the opening size
of the printhead nozzle hole.
[0008] The main control cabinet is connected to a power clock end
of the signal generator, and the output end of the signal generator
is connected to the printhead controller to control the switch of
the printhead. The prototyping table is positioned under the
printhead, and connected with a cell activity detecting device for
detecting cell activity of a printed product. After a detection at
the cell activity detection device, it is determined whether the
configuration of the printer is appropriate according to whether
the cell activity is good or not. If the configuration is
inappropriate, the cause of the inappropriateness is determined and
is fed back to the printhead controller for a real-time adjustment
to ensure good cell activity.
[0009] Preferably, the cell activity detecting device may include a
mechanical transport arm, an operation table, a reagent kit, and a
detector. The function of the mechanical transport arm is to drive
the operation table through the mechanical transport arm to
complete the transport of tissues and organs to be tested.
[0010] The mechanical transport arm is connected with the operation
table. A circular lifting platform is provided in the center of the
operation table. The function of the circular lifting platform is
to immerse the tissue organ to be tested into a reagent in the kit
through the lifting platform. The reagent kit and the detector are
fixed on the operation table, and the detector is connected with
the upper PC through a signal line.
[0011] The working principle of the detection of cell activity of
the printed tissues and organs is a colorimetric method. For
example, a WST-8 reagent is used and is reduced by dehydrogenase in
the cell mitochondria to a highly water-soluble yellow formazan
product under the action of an electron carrier 1-Methoxy PMS
(phenazinium methylsulfate), where the amount of the formazan
product is proportional to the amount of living cells. The amount
of living cells can be reflected by measuring the absorbance value
at a wavelength of 450 nm using the detector.
[0012] Preferably, the material conveying hoses and the
corresponding printheads are respectively five.
[0013] Preferably, the printhead is a detachable printhead and can
automatically adjust the size of the printhead nozzle hole.
[0014] Preferably, the activity detection device can form
self-feedback with the printhead controller based on the printed
cell activity to adjust the configuration of the printer.
[0015] The 3D bio-printer of the present disclosure is divided into
two parts: an upper computer and a lower computer. The upper
computer is a PC end. Various parameter settings of 3D printing can
be realized through the PC end, including a minimum step value of
movement in the XYZ three axes, selection of materials in each
printhead, graphic setting of 3D layered printing, parameter
setting and real-time status reading of the conveying hose,
parameter setting and status reading of the prototyping table,
display of detection status of the cell activity detection device,
and display of various parameters for the operation of the 3D
printer.
[0016] The lower computer part is a hardware structure part of the
3D bio-printer. The upper computer and the lower computer are
connected by an Ethernet port or wirelessly, and data is
transmitted by TCP/IP (Transmission Control Protocol/Internet
Protocol). A user may input parameters into the upper computer
according to the requirement of printing. After receiving an
instruction, the upper computer decodes the instruction and then
transmit it to the printhead controller for communication to drive
the printer to work.
[0017] The 3D bio-printer capable of detecting cell activity
disclosed in the present disclosure may include a hardware
constitution system and a running logic control system, thereby
overcoming the existing technical problems at present. By adding
the cell activity detection table in the 3D printer work case, it
is possible to measure cell activity intermittently in the process
of cell printing, which solves the problem that the cell activity
of the printed tissue and organ cannot be detected in real time in
the process of 3D printing. In the 3D printer of the present
disclosure, a plurality of printing printheads are connected to the
printhead base and can provide bio-printing of various raw
materials at the same time. Since the printheads are detachable,
the printheads with different apertures may be replaced according
to the installed biological materials to realize multi-biological
material printing. In the 3D bio-printer of the present disclosure,
the conveying hose is connected to the printhead base for storing
raw materials required for printing. An automatic supply of raw
materials is realized by the air pump and the air pump control box,
thereby reducing unnecessary human operation. Through the upper
computer software, the method of printing tissues and organs,
optimal settings for layered printing, biological materials
corresponding to the printheads, minimum moving distance of the
printheads, reports of results of cell activity detections, and the
actual operation status of the system in operation are set.
[0018] The present disclosure has the following beneficiary effects
as compared with prior art. The 3D bio-printer capable of detecting
cell activity of the present disclosure can detect cell activity in
the process of printing, which ensures that the printed biological
tissues maintain biological activity. It can supply
multi-biological raw materials and realize multi-biological
material printing, which ensures an environment suitable for
biological material printing. The design of detachable printheads
is convenient for replacing the printheads. The cell activity
detection table can form self-feedback with the printhead
controller based on the printed cell activity to adjust the
configuration of the printer.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] The present disclosure will be further described below with
reference to the attached drawings.
[0020] FIG. 1 illustrates a schematic structural view of a 3D
bio-printing device of the present disclosure;
[0021] FIG. 2 illustrates a working logic diagram of the 3D
bio-printing device of the present disclosure;
[0022] FIG. 3 illustrates a schematic diagram of a 3D bio-printing
PC end of the present disclosure;
[0023] FIG. 4 illustrates an internal selection circuit diagram of
a printhead controller of the present disclosure;
[0024] FIG. 5 illustrates a circuit diagram of a printhead
temperature control module of the present disclosure; and
[0025] FIG. 6 is a circuit diagram of a motor drive of the present
disclosure.
DETAILED DESCRIPTION
[0026] The technical solutions of the present disclosure will be
described in detail below with reference to the embodiments, but
the scope of protection is not limited thereto.
[0027] The below is a detailed description of the present
disclosure with reference to specific preferred embodiments, and
the specific embodiments of the present disclosure are not limited
thereto. For those of ordinary skill in the art, a number of simple
derivations or substitutions may be made without departing from the
present disclosure. All these derivations and substitutions should
be considered as belonging to the scope of protection of the
present disclosure determined by the submitted claims.
[0028] As shown in FIGS. 1 and 2, the 3D bio-printer capable of
detecting cell activity of the present disclosure is divided into
two parts: an upper computer 102 and a lower computer. The main
components of the lower computer include a main control cabinet
104, a signal generator 106, a stepping motor 108, a mechanical arm
110, a temperature controller 112, an air pump 114, an air pump
control box 116, an air tank 118, and a cell activity detection
table 120.
[0029] A printed circuit board for single-chip microcomputer is
stored in the main control cabinet 104, and a written control
program is stored in a microcontroller. The microcontroller drives
the peripheral hardware circuits by the control program and
controls the operating part and the core algorithm part of the
printer. The microcontroller also drives a programmable logic
control device as a signal generator to provide various
frequencies, waveforms, and output level electrical signals.
[0030] The stepping motor 108 is an open-loop control motor which
converts received electrical pulse signals of different frequencies
into angular displacement and linear displacement, and controls a
printhead 122 to operate at different speeds and directions in the
XYZ three axes.
[0031] The mechanical arm 110 is equivalent to a scaffold, and the
stepping motor 108 controls the mechanical movement of the
mechanical arm 110. The mechanical arm 110 is equipped with three
stepping motors which respectively control the movement and the
distance of movement in the X-axis direction, the Y-axis direction,
and the Z-axis direction.
[0032] The 3D printer work case includes a printhead base 124 which
is mounted on the mechanical arm 110 for fixing the printhead 122.
The printhead base 124 is also connected with a conveying hose 126
which stores and conveys the biological raw materials required for
printing.
[0033] The printhead 122 is equipped with a temperature sensor
which can feed back the printing temperature of the printhead 122
in real time to ensure that the temperature of the printhead 122 is
within a normal printing range. When the temperature exceeds the
normal range, the temperature controller 112 may be driven in real
time to adjust the temperature to keep the temperature steady.
[0034] The conveying hose 126 is connected to a printhead
controller 128, and the bottom of the printhead controller 128 is
connected with the printhead 122 which can print the materials onto
a prototyping table 130.
[0035] The prototyping table 130 is connected with the cell
activity detection table 120 for detecting cell activity of the
printed tissues and organs. If the printed cell activity rate does
not meet the requirements, configuration defect determination is
performed. After the cause is determined, it is fed back to the
printhead controller 128 to form an automatic adjustment of the
configuration of the printer.
[0036] The conveying hose 126 is also connected with the
temperature controller 112 which controls the temperature of the
conveying hose to ensure the temperature required for the activity
of the biological materials.
[0037] The air pump 114 is connected to the top of the conveying
hose 126 and is also connected with the air tank 118 and the air
pump control box 116 respectively. The printer can memorize the
working process of printing, save the printing process in the case
of power outage, and can continue printing after power-on, thereby
improving work efficiency. The user at the PC end can choose to
connect with the main control cabinet 104 through an Ethernet port
or wirelessly.
[0038] As shown in FIG. 3, an operation interface of the upper
computer of the 3D bio-printer is illustrated. It is used to
configure the printer on the upper computer interface, select the
materials for printing and printing injection devices, and set the
parameters of the printer.
[0039] FIG. 4 is an example internal circuit diagram of the
printhead controller 128, which includes a control chip and a
selector, and can perform the function of selecting injection
devices. FIG. 5 is an example temperature control module diagram,
and the temperature is adjusted through the circuit. FIG. 6 is a
standard motor drive circuit performing the drive of the motor so
that the motor is used to drive the movement of a printing
printhead.
[0040] In the 3D bio-printing device of the embodiment, the PC end
communicates with the main control cabinet by TCP/IP (Transmission
Control Protocol/Internet Protocol). A user may set the work mode
at the PC end according to his/her own needs. After setting, the
data is sent to the main control cabinet via an Ethernet port, and
the main control cabinet processes decoding and executes operations
after receiving the instruction. The main control cabinet has a
self-inspection function. It performs self-inspection before the
operation, and prepares for work after the self-inspection verifies
that the system is normal.
[0041] In some embodiments, the 3D bio-printer may use five
printhead printing modes, five signal generators, three stepping
motors, five printhead controllers, five air tanks, five air pumps,
five conveying hoses, and five temperature controllers.
[0042] A printed circuit board for single-chip microcomputer is
stored in the main control cabinet, and a written control program
is stored in a microcontroller. The microcontroller drives the
peripheral hardware circuits by the control program and controls
the operating part and the core algorithm part of the printer. The
microcontroller also drives a programmable logic control device as
a signal generator to provide various frequencies, waveforms, and
output level electrical signals.
[0043] The stepping motor is an open-loop control motor which
converts received electrical pulse signals of different frequencies
into angular displacement and linear displacement, and controls a
printhead to operate at different speeds and directions in the XYZ
three axes. The mechanical arm is equivalent to a scaffold, and the
stepping motor controls the mechanical movement of the mechanical
arm.
[0044] The mechanical arm is equipped with three stepping motors
which respectively control the movement and the distance of
movement in the X-axis direction, the Y-axis direction, and the
Z-axis direction. Five printhead bases are installed in sequence on
the mechanical arm, and two communication data by the 485
communication protocol are led out from each printhead base to
return the data to the main control cabinet. The main control
cabinet obtains the specific real-time position by analyzing data
in the microcomputer.
[0045] The conveying hose is installed under the printhead base for
storing various biological raw materials required for printing. The
conveying hose is connected with a temperature sensor which can
sense the temperature inside the conveying hose and adjust the
temperature in real time to control the temperature inside the
conveying hose for the ease of material storage. The connecting
part between the printhead base and the top of the conveying hose
is connected with an external air pump through a hose, and a filter
screen is arranged in the middle to strictly ensure a sterile
environment inside the conveying hose.
[0046] The air pump is connected with the air tank and the air tank
control box, and its function is to control the air pressure
difference inside the hose by controlling the running of the motor
via the air pump control box according to the requirements so as to
control the material feeding speed.
[0047] The conveying hose is connected to the printhead controller,
and the bottom of the printhead controller is connected with the
printhead. The main control cabinet is connected to a power clock
end of the signal generator, and the output end of the signal
generator is connected to the printhead controller. The printhead
controller selects the switch corresponding to the printhead
through a software driven selector, and can control the working
time of the printhead by setting the time.
[0048] The printhead can be separated by this design. By connecting
the printhead controller to the main control cabinet instead of
directly connecting the printhead to the main control cabinet, it
is only necessary to replace printheads with different apertures
for replacing different biological raw materials. The printing
printhead performs printing on the prototyping table. The
prototyping table is connected with the cell activity detection
table to form an enclosed working environment, which has a built-in
high-precision temperature and humidity sensor and is a sterile
environment. The tissues and organs printed on the prototyping
table can be sent to the cell activity detection table for
detection of the cell activity at a certain time interval. The
detection time interval can be set via the upper PC end. It is
determined according to the activity of the system whether the
printer configuration meets the printing requirements, and if not,
a feedback is formed and the configuration is automatically
adjusted.
[0049] The working process of the cell activity detection table is
as follows. When it reaches the detection time set at the PC end, a
high-precision external timer is used for timing. When it reaches
the set detection time, the main controller receives a trigger
signal to control the movement of the mechanical arm to move the
operation table to the prototyping table to obtain the tissue organ
to be detected, and places the tissue organ on the circular lifting
platform. The operation table is returned to the original position
by the movement of the mechanical arm, and the tissue organ is
immersed in a WST-8 reagent via the circular lifting platform.
After reaction for a period of time, the circular lifting platform
is raised to the original position. The operation table is moved
outward by the mechanical arm, and the water-soluble yellow
formazan product is subjected to light absorption detection by a
detector. After the detection, the operation table is moved to the
prototyping table by the mechanical arm, and the tissue organ is
placed back to the original position at the prototyping table. A
detection report is displayed at the PC end. The printing will
continue if the detected cell activity meets the requirements. If
there is a defect in the detected cell activity, the cause of the
problem is determined and fed back to the controller to
automatically adjust the printer configuration so as to ensure cell
activity.
[0050] The various embodiments described above are provided by way
of illustration only and should not be construed to limit the scope
of the disclosure. Various modifications and changes may be made to
the principles described herein without following the example
embodiments and applications illustrated and described herein, and
without departing from the spirit and scope of the disclosure.
* * * * *