CN107418998A - Particulate control method, biometric print method and biological construct - Google Patents
Particulate control method, biometric print method and biological construct Download PDFInfo
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- CN107418998A CN107418998A CN201610822794.9A CN201610822794A CN107418998A CN 107418998 A CN107418998 A CN 107418998A CN 201610822794 A CN201610822794 A CN 201610822794A CN 107418998 A CN107418998 A CN 107418998A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/24—Methods of sampling, or inoculating or spreading a sample; Methods of physically isolating an intact microorganisms
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
Abstract
The present invention relates to micromanipulation field, more particularly to a kind of particulate control method.Particulate control method provided by the present invention, successively including step a:The bottom of suction elements is set to form liquid film；With step b：Particulate is drawn using suction elements, particulate is maintained at the bottom of suction elements and is contacted with liquid film.Relative to existing particulate control method, particulate control method provided by the present invention, by forming liquid film in suction elements bottom in advance, and particulate is maintained at the position that suction elements bottom contacts with liquid film, the damage to particulate can be effectively reduced, this contributes to particulate to keep default form and/or good bioactivity.
Description
Technical field
The present invention relates to micromanipulation field, more particularly to a kind of particulate control method, biometric print method and life
Thing construct.
Background technology
In the prior art, the pipettor such as generally use liquid-transfering gun, minim pipette and syringe manipulates particulate, root during use
The liquid-transfering gun of suitable volumes, the minim pipette of suitable syringe needle bore or syringe etc. are selected according to the size of particulate, is manually operated
These pipettors, by negative pressure caused by pipettor imbibition, particulate is drawn in the tube chamber of corresponding pipettor, realized to particulate
Seizure, particulate is positioned over setting placement location by malleation caused by pipettor tapping again after displacement, realized to particulate
Placement.
However, this existing particulate control method, because it needs to suck particulate in the tube chamber of pipettor, therefore,
The damage to particulate is easily caused, such as causes particulate can not keep default form, for another example for the micro- of bioactivity
Grain, can also damage because of the friction of lumen wall, cause cellular damage or death, influence the bioactivity of these particulates, with
Cause these particulates in influence to realize corresponding biological function, finally influence the biological function of its biological construct formed.
Moreover, this existing particulate control method fully relies on absorption of the negative pressure realization of pipettor to particulate, it is necessary to apply larger
Suction force, this aspect can improve the requirement to aspiration technique, and difficulty is drawn in increase, reduces manipulation success rate, on the other hand,
Larger suction force can also be further exacerbated by the damage to particulate；Also, the simple absorption realized by negative pressure to particulate, draws
Controllability is poor, often occurs certain and once draws multiple particulates, another situation that can not be but drawn onto particulate, it is difficult to ensures each
The uniformity of absorption, this also causes unnecessary trouble to operating steps such as follow-up displacements and/or placement.
It should be noted that the content described by this part is intended merely to conveniently understand, it is not construed as recognizing or secretly
It is prior art to show these contents.
The content of the invention
A technical problem to be solved by this invention is：Existing particulate control method, easily causes the damage to particulate
Wound.
In order to solve the above-mentioned technical problem, first aspect present invention provides a kind of particulate control method, and it includes successively
Following steps：
Step a:The bottom of suction elements is set to form liquid film；With
Step b：The suction elements that liquid film is formed using bottom draw particulate, particulate is maintained under suction elements
End simultaneously contacts with liquid film.
Alternatively, in step a, liquid is drawn in advance by using suction elements form the bottom of suction elements
Liquid film.
Alternatively, in step a, the liquid that suction elements are drawn in advance is the liquid of submergence particulate.
Alternatively, in stepb, after particulate being drawn into the bottom of suction elements using suction elements, stop drawing
Action, makes particulate be maintained at the bottom of suction elements in the presence of the tension force of negative pressure and liquid film.
Alternatively, in stepb, the suction elements for liquid film being formed using one or at least two bottoms draw particulate,
Each suction elements only draw single particulate.
Alternatively, particulate control method also includes being arranged at the step c after step b：Suction elements are moved to particulate
Setting placement location top, and using suction elements driving particulate depart from suction elements bottom and be placed on setting
Placement location.
Alternatively, in step c, suction elements are moved down, particulate is directly contacted with setting placement location, makes particulate
Depart from suction elements bottom in the presence of the adhesion and self gravitation between setting placement location, and be placed on and set
Determine placement location.
Alternatively, in step c, particulate is sprayed using suction elements, makes particulate in malleation and self gravitation
Effect is lower to depart from the bottom of suction elements, and is placed on setting placement location.
Alternatively, when particulate is placed on setting placement location by suction elements, still residue has part in advance in suction elements
The liquid of absorption.
Alternatively, particulate control method also includes being arranged at the step d after step c：Will be remaining pre- in suction elements
The liquid discharge first drawn.
Alternatively, the particle diameter of particulate is 0.5-3mm.
Alternatively, particulate is the gel state particulate that can maintain its own structural stability in its natural state.
Alternatively, particulate is biological brick.
Second aspect of the present invention additionally provides a kind of biometric print method.The biometric print method utilizes particulate of the invention
Control method manipulates the biological brick as particulate.
Third aspect present invention additionally provides a kind of biological construct.The biological construct utilizes biometric print of the invention
It is prepared by method.
Relative to existing particulate control method, particulate control method provided by the present invention, by advance in drawing section
Part bottom forms liquid film, and particulate is maintained at into the position that suction elements bottom contacts with liquid film, can effectively reduce pair
The damage of particulate, help to make particulate keep default form and/or good bioactivity.
By referring to the drawings to the present invention exemplary embodiment be described in detail, further feature of the invention and
Its advantage will be made apparent from.
Brief description of the drawings
In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing
There is the required accompanying drawing used in technology description to be briefly described, it should be apparent that, drawings in the following description are only this
Some embodiments of invention, for those of ordinary skill in the art, without having to pay creative labor, may be used also
To obtain other accompanying drawings according to these accompanying drawings.
Fig. 1 shows one embodiment of the control method of biometric print unit of the present invention, wherein, Fig. 1 a and Fig. 1 b are shown
Step a, Fig. 1 c show that step b, Fig. 1 d and Fig. 1 e show that step c, Fig. 1 f show step d.
In figure：
10th, liquid-transfering gun；20th, biological brick；30th, memory cell；40th, matrix is printed.
Embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete
Site preparation describes, it is clear that described embodiment is only part of the embodiment of the present invention, rather than whole embodiments.Below
Description only actually at least one exemplary embodiment is illustrative, is never used as to the present invention and its application or makes
Any restrictions.Based on the embodiment in the present invention, those of ordinary skill in the art are in no development creative work premise
Lower obtained every other embodiment, belongs to the scope of protection of the invention.
It may be not discussed in detail for technology, method and apparatus known to person of ordinary skill in the relevant, but suitable
In the case of, the technology, method and apparatus should be considered as authorizing part for specification.
In the description of the invention, it is to be understood that the noun of locality such as " forward and backward, upper and lower, left and right ", " laterally, vertical,
Vertically, orientation or position relationship indicated by level " and " top, bottom " etc. are normally based on orientation or position shown in the drawings and closed
System, it is for only for ease of the description present invention and simplifies description, in the case where not making opposite explanation, these nouns of locality do not indicate that
There must be specific orientation with the device or element for implying meaning or with specific azimuth configuration and operation, therefore can not manage
Solve as limiting the scope of the invention；The noun of locality " inside and outside " refers to relative to inside and outside each part profile in itself.
In the description of the invention, it is to be understood that limit parts using the word such as " first ", " second ", only
It is for only for ease of and corresponding parts is distinguished, does not such as have Stated otherwise, above-mentioned word does not have particular meaning, therefore not
It is understood that as limiting the scope of the invention.
As used herein, term " biological construct " refers to, artificial constructed, two-dimentional or three-dimensional containing cell
Structure.In certain preferred aspects, biological construct is three-dimensional construct, tissue precursor, artificial organ or artificial
Organ.
As used herein, term " biological brick " is a kind of module list with bioactivity for building organism
Member, during its individualism, its steric configuration can be maintained, it can be used for multiple fields, such as biometric print (such as 3D biometric prints),
The field such as organizational project and regenerative medicine.Wherein, can be as the basis of 3D biometric prints in 3D biometric prints field, biological brick
Unit.The preferable structure and composition of biological brick is：Celliferous stratum nucleare is wrapped, wherein, cell can be grown, be bred, being divided
Change or migration, stratum nucleare are made up of Biodegradable material, and required material is provided for the vital movement of cell；With encapsulation
The shell of stratum nucleare, shell are located at the outside of stratum nucleare, are made up of Biodegradable material, and are provided for the stratum nucleare and cell of inside
Mechanics is protected.The biological brick of this preferred structure shows as biological active microsphere.
As used herein, term " gel state particulate " is the total of the based fine particles that have similar characteristic with biological brick
Claim, it is able to maintain that the stability of its own structure in its natural state.
Fig. 1 shows one embodiment of particulate control method of the present invention.Reference picture 1, particulate behaviour provided by the present invention
Prosecutor method, comprises the following steps successively：
Step a:The bottom of suction elements is set to form liquid film；
Step b：The foregoing suction elements that liquid film is formed using bottom draw particulate, particulate is maintained at the drawing section
The bottom of part simultaneously contacts with liquid film.
The particulate control method of the present invention, particulate is no longer drawn to pipe by it when catching acquisition particulate using suction elements
In chamber, but particulate is maintained to the bottom of suction elements, due to abrasion of the lumen wall to particulate can be avoided and to micro-
The change of grain form, therefore, it is possible to effectively prevent the tube chamber of suction elements to the damage caused by particulate；Moreover, the present invention exists
Before Micro-picking to suction elements bottom, the bottom of suction elements is set to be formed for the liquid with asperity contact in advance
Film, because the liquid film further can keep apart the bottom of particulate and suction elements, make under particulate and suction elements
End mediate contact, accordingly it is possible to prevent particulate because with the direct rigid contact in the bottom of suction elements and it is mechanically damaged,
Further reduce particulate damage suffered during manipulation.In addition, particulate is no longer drawn in tube chamber by the present invention, but will
Particulate is maintained at the bottom of suction elements, and this can also improve the controllability of absorption, it is easier to ensures to draw manipulation every time
Uniformity, and the follow-up implementation for shifting and/or placing of being more convenient for.
It can be seen that relative to existing particulate control method, particulate control method provided by the present invention, by inhaling in advance
Take lower portion to form liquid film, and particulate is maintained at the position that suction elements bottom contacts with liquid film, can effectively subtract
Few damage to particulate, this contributes to particulate to keep default form and/or good bioactivity.
In addition, the present invention makes suction elements bottom be pre-formed liquid film, its benefit also resides in：(1) preformed liquid
The particulate that film can treat absorption plays sucking action so that in suction process, particulate is not only by the negative pressure of suction elements
Effect, also simultaneously by the surface tension effects of liquid film, this aspect can reduce the negative pressure applied needed for suction elements, not only
Aspiration technique requirement can be reduced, chance of success is drawn in increase, additionally it is possible to mitigate damage of the suction force to particulate, on the other hand this
Particulate can also be made to be more securely held in the bottom of suction elements, be easy to shift particulate, improve particulate manipulation
The stability and reliability of process；(2) if not forming liquid film in advance, to realize and particulate is maintained at suction elements bottom
Purpose, the size of particulate have to be larger than the lumen diameter of suction elements, and this could be protected the particulate for causing only large-size
Hold in the bottom of suction elements, and the particulate of reduced size is then difficult to be grasped based on this non-suction-type particulate acquisition modes
Control, and the present invention is pre-formed liquid film in suction elements bottom, can effectively overcome this non-suction-type particulate acquisition modes
Requirement to particle size, expand the scope of application of this non-suction-type particulate acquisition modes so that more particulates can be
It is steered by the premise of compared with Small loss, such as the manipulation of the particulate to particle diameter in the range of 0.5-3mm can be realized.
The formation of liquid film in step a of the present invention, can there is a numerous embodiments, for example, can by way of smearing shape
Into.Wherein preferably, liquid can be drawn in advance using suction elements to make suction elements bottom form the liquid film.It is good
Be in, liquid film forming is more convenient, and the liquid sucked inside suction elements can also moisten the lumen walls of suction elements,
The damage to particulate can further be reduced so as to all form liquid film inside the bottom of suction elements and tube chamber.
Further, particulate control method of the invention can also include being arranged on the step c after step b：It will draw
Part is moved to the top of the setting placement location of particulate, and departs from the bottom of suction elements using suction elements driving particulate
And it is placed on setting placement location.Based on this, particulate control method of the invention can not only realize that the seizure to particulate obtains
Take, displacement and placement to particulate can also be realized.
Wherein it is possible to the placement to particulate is realized by direct modes of emplacement.That is, in step c, can move down
Suction elements, particulate is directly contacted with setting placement location, make adhesion of the particulate between placement location set and oneself
Depart from suction elements bottom in the presence of body gravity, and be placed on setting placement location.It is real based on the direct modes of emplacement
Now to the placement of particulate, it is micro- need to only make it that the adhesion between particulate and setting placement location is more than with particulate self gravitation sum
Tension force and negative pressure sum between grain and liquid film, due to need not be applied just to particulate by suction elements in placement process
Pressure, therefore, can further avoid the pressure of suction elements from causing to damage to particulate in particulate placement process.
In addition, the present invention can also realize the placement to particulate by spray regime.That is, in step c, can utilize
Suction elements are sprayed particulate, particulate is departed from the bottom of suction elements in the presence of malleation and self gravitation, and
It is placed on setting placement location.The modes of emplacement, particulate is positioned over setting using malleation during suction elements tapping and placed
Position, placement efficiency can be effectively improved.
When particulate is placed on setting placement location by suction elements, still residue can be made to have part in advance in suction elements
The liquid of absorption, even if also suction elements are not drained by the liquid of its internal advance absorption.So operating is advantageous in that, can
To reduce the liquid at setting placement location as far as possible, make at setting placement location still with particulate in itself based on, reduce and draw in advance
Liquid the influence of function is realized in setting placement location to particulate.Based on this, further, particulate of the invention manipulates
Method can also include being arranged at the step d after step c：The remaining liquid drawn in advance in suction elements is discharged.It is logical
Setting steps d is crossed, can continue to realize the manipulation or otherwise utilized to another particulate in order to suction elements, improve efficiency.
The particulate control method of the present invention goes for various particulates, the dome-type that is particularly suitable for use in, spheroid shape or ball-type
Etc. the body shape thing for possessing more apparent curved surface, and the soft texture that is particularly suitable for use in, non-rigid (such as non-solid, non-rigid surface)
Particulate, wherein it is highly preferred that the particulate control method of the present invention goes for biological brick etc. with bioactivity and in nature
The gel state particulate of its own structural stability is able to maintain that under state.
Particulate control method of the present invention is described further i.e. embodiment with reference to shown in Fig. 1 below.At this
In embodiment, particulate control method of the invention is applied to biometric print process, and the manipulation to particulate is included to biological brick 20
Draw, shift and place, that is, the particulate of the embodiment is biological brick 20；Biological brick 20 is pre-stored within memory cell 30
In (such as in each hole position of orifice plate), and biological brick 20 is liquid-immersed in advance in memory cell 30, so that biological brick 20
Preferably activity is kept in liquid environment；Suction elements are liquid-transfering gun 10, and the liquid-transfering gun 10 is controllable pressure liquid-transfering gun, with
It is easy to control suction to bleed off pressure power, liquid-transfering gun 10 can be, but not limited to have 5 gears, and each gear corresponds to different pressure, also right
Answer different liquid volumes；Placement location is set on printing matrix 40, print position is alternatively referred to as set in the embodiment,
It can be stereochemical structure (such as revolving raw instrument column) to print matrix 40, or planar structure, this can shape as needed
Into biological construct selected.Specifically, biological brick 20 of the embodiment using particle diameter as 2mm is manipulation object, therewith phase
The liquid-transfering gun 10 of adaptation can select the liquid-transfering gun 10 that bore is 0.4mm, 0.5mm or 1mm etc., certainly, in other embodiments,
The particle diameter of biological brick 20 and the bore of liquid-transfering gun 10 can also be other sizes, as long as the two is adapted to.
In this embodiment, particulate control method comprises the following steps successively：
Step a：As shown in Figure 1a, first, liquid-transfering gun 10 is adjusted to absorbing pattern, and by gear be set as 2 grades (such as can
Think 50 μ l), complete the setting to liquid-transfering gun 10；Then, as shown in Figure 1 b, liquid-transfering gun 10 is moved to and is stored in memory cell 30
In biological brick 20 top (be preferably directly over), complete the regulation to the position of liquid-transfering gun 10, afterwards, start imbibition program,
Start imbibition, the liquid of submergence biological brick 20 is drawn first with liquid-transfering gun 10, the liquid levels in liquid-transfering gun 10 is first risen to
Between 1-2 shelves (such as can be 40 μ l), the liquid drawn in advance forms liquid film in the bottom of liquid-transfering gun 10；
Step b：As illustrated in figure 1 c, continue to draw using liquid-transfering gun 10, make biological brick 20 in the negative pressure and liquid of liquid-transfering gun 10
It is drawn in the presence of the surface tension of film to the bottom of liquid-transfering gun 10, and is contacted with liquid film, now stops sucking action, stop
Only after sucking action, although biological brick 20 can somewhat move downwards in the presence of liquid inertia flowing, in negative pressure and liquid film
Biological brick 20 remains able to be maintained at the bottom of liquid-transfering gun 10 in the presence of tension force, now the liquid liquid inside liquid-transfering gun 10
Face rises to 2 grades, completes the seizure to biological brick 20 and obtains (being referred to as capturing)；
Step c；As shown in Figure 1 d, the liquid-transfering gun 10 that bottom is maintained to biological brick 20 is moved at printing matrix 40,
Liquid-transfering gun 10 is located at the top (directly over being preferably) of the setting print position corresponding to the biological brick 20, complete to biological brick
20 displacement；Then, as shown in fig. le, liquid-transfering gun 10 is adjusted to tapping pattern, setting tapping gear between 1-2 shelves (such as
Can be 10 μ l in 50 μ l), start tapping, make biological brick 20 in the malleation and biological brick 20 self gravitation of liquid-transfering gun 10
The lower bottom for departing from liquid-transfering gun 10 of effect, falls to setting print position, completes the placement to biological brick 20, namely completion pair
The printing of biological brick 20；
Step d：As shown in Figure 1 f, the liquid-transfering gun 10 for inside still being remained with to suction liquid in advance is removed, away from beating
Matrix 40 is printed, and liquid-transfering gun 10 is moved into suitable drain location, such as can move at special waste liquid tank, discharges liquid-transfering gun
Remaining liquid (such as can be remaining 40 μ l in 50 μ l), completes the discharge to remaining liq in 10.
In this embodiment, the liquid sucked in advance in liquid-transfering gun 10, the muzzle inwall and rifle of liquid-transfering gun 10 can be soaked
Mouth tip so that (namely bottom of suction elements) forms liquid film at the muzzle of liquid-transfering gun 10, and the liquid film can be in liquid-transfering gun
10 continue draw biological brick 20 when, avoid muzzle from directly being contacted with biological brick 20, so as to prevent the form of biological brick 20 and
Bioactivity is suffered damage and destroyed because with the direct rigid contact of muzzle.
Also, because liquid film can separate muzzle and biological brick 20, the biological brick 20 of muzzle diameter is less than even if particle diameter
It can be maintained in the presence of liquid film and negative pressure at muzzle, therefore, by setting liquid film effectively to overcome non-suction
Requirement of the particulate acquisition modes to the particle diameter of biological brick 20, expand the scope of application of this non-suction particulate acquisition modes so that more
More specifications and a greater variety of biological bricks 20 can be steered on the premise of by compared with Small loss, and due to the life compared with small particle
Thing brick 20, the cell quantity included inside it is relatively fewer, relatively low for the demand of nutrition supply, therefore, utilizes liquid film
Realize to the non-suction-type acquisition compared with small particle biological brick 20, be also beneficial to preferably maintain biological brick 20 in print procedure
Bioactivity, and help to finally give the biological construct with more preferable bioactivity.
Moreover, the liquid film formed in advance at muzzle, can play sucking action to the biological brick 20 of rear absorption so that
Biological brick 20 is not only by suction function, also simultaneously by the surface tension effects of liquid film, on the one hand, this can reduce liquid-transfering gun
The negative pressure applied needed for 10, can not only reduce aspiration technique requirement, and chance of success is drawn in increase, additionally it is possible to mitigates suction force pair
The damage of biological brick 20；On the other hand, this can also be such that biological brick 20 is more securely held at muzzle, improve crawl process
Fastness, and cause biological brick 20 can be securely held in during being shifted at muzzle, be not easy to drop, improve
The stability and reliability of shifting process；Another further aspect, liquid film can make biological brick 20 from by straight by being suctioned out in memory cell 30
To being in all the time in liquid environment during being placed on setting print position, and liquid environment to be biological brick 20 keep biology
One key factor of activity, therefore, by setting liquid film, can cause biological brick 20 to remain on energy in shifting process
Good activity is enough kept, improves the success rate of biometric print.
In addition, in this embodiment, liquid film is that the liquid for being drawn submergence biological brick 20 in advance using liquid-transfering gun 10 is formed,
This forms the situation of liquid film with respect to the independent liquid drawn outside memory cell 30, can simplify particulate control method
The step of, manipulation efficiency, also, the liquid film that the liquid for submerging biological brick 20 is formed are improved, is formed relative to other liquid
Liquid film for, there is more excellent biocompatibility between biological brick 20, can preferably be kept during manipulation
The bioactivity of biological brick 20.
Furthermore in this embodiment, each manipulation process only manipulates a biological brick 20, namely in stepb, Mei Geyi
10, liquid rifle draws single biological brick 20, so can not only reduce manipulation difficulty, increase manipulation chance of success；Moreover, base
In this, it is possible to achieve and " with point paint shape " biometric print pattern, you can with by biological brick 20 according to default one grain of arrangement mode
Be placed in printing matrix 40 surface, and without again as " shape is painted with line " in the prior art continuous extruded type biometric print pattern that
Sample is, it is necessary to which material to be printed (cell suspension for including biological brick 20, adhesive and hydrogel etc.) to be placed in container and rely on
Piston or nozzle drive material to be printed in the presence of package flow into single-row linear convergent rate, because the biology of " painting shape with point " is beaten
Watermark patterns, it can more accurately ensure interval and locus between each biological brick 20 etc., make biological brick 20 more accurately
Arrange on demand, therefore, it is possible to realize more accurately biometric print process, help to obtain the more accurate biological construct of shape,
And for another angle, this can also reduce limitation of the biometric print technology to biological construct shape to be printed so that
Biometric print technology can realize the printing to more biological constructs of different shapes, effectively expand the suitable of biometric print technology
With scope, also, because compared with the cell suspension of flowable state, single biological brick 20 itself has preferably sizing energy
Power, therefore, directly manipulate biological brick 20 and carry out biometric print, can save and the step such as follow-up heat treatment is carried out to cell suspension
Suddenly, the precision architecture structure of three-dimensional tissue can more directly be realized.
In addition, in the step c of the embodiment, when biological brick 20 is positioned over into setting print position, in liquid-transfering gun 10 still
So remain with the liquid sucked in advance.Based on this, on the one hand, in placement process, the partially liq in suction elements can be negative
Setting print position is placed in the presence of pressure together with particulate, this partially liq is advantageous to hold in print procedure relaying continuation of insurance
The bioactivity of biological brick 20, on the other hand, in placement process, and can control is placed on setting with biological brick 20 and beaten
The liquid of print position is unlikely to excessive, can effectively reduce the liquid outside excessive biological brick 20 and biological brick 20 is positioned and given birth to
The influence of thing function, help to realize that biological brick 20 is more accurately located, and ensure that biological brick 20 realizes predetermined biological function.
It can be seen that the particulate control method of the present invention is applied into biometric print field, biological brick 20 liquid-transfering gun is not sucked into
Inside 10, and by the way that portion forms liquid film at muzzle in advance, and biological brick 20 is maintained to the position contacted at muzzle with liquid film,
Liquid-transfering gun 10 can effectively be reduced to the mechanical damage of biological brick 20 and biological brick 20 is made because the negative pressure applied is larger
Into stress injury, and can make under biological brick 20 is in liquid environment during whole manipulation, to keep good biology
Activity, these both contribute to biological brick 20 and default form and good bioactivity are kept during manipulation, finally give
More accurate and more excellent bioactivity biological construct；Moreover, by the surface tension effects of liquid film, also cause to biological brick
20 crawl and shifting process are more stable and reliable, can effectively improve manipulation efficiency and manipulation success rate, realize more smart
Quasi- ground biometric print.
So present invention also offers a kind of particulate control method using the present invention to the biological brick progress as particulate
The biometric print method of manipulation, and the biological construct that a kind of biometric print method using the present invention is prepared.
It should be noted that in above-described embodiment, the side manipulated using a suction elements to particulate is merely illustrated
Method, it is to be understood by those skilled in the art that disposably can also be manipulated using multiple suction elements in the present invention multiple simultaneously
Particulate, for example, in other embodiments, can be inhaled using multiple liquid-transfering guns 10 including a pipette tips to multiple particulates
Take, or, multiple particulates can also be drawn using one or more liquid-transfering guns 10 for including multiple pipette tips, so can
Further improve manipulation efficiency；Moreover, in other embodiments, suction elements are also not limited to a kind of implementation of above-mentioned liquid-transfering gun 10
Mode, it can also be other pipettors such as pipette, buret or syringe.In addition, mentioned in the present invention " step a " and
" order of representation such as step b " it is front and rear, " step a " and " step b " can be close to two steps, " step a " and " step
Can also there are other steps between b ".
The exemplary embodiment of the present invention is the foregoing is only, is not intended to limit the invention, all spirit in the present invention
Within principle, any modification, equivalent substitution and improvements made etc., it should be included in the scope of the protection.
Claims (15)
1. a kind of particulate control method, it is characterised in that comprise the following steps successively：
Step a:The bottom of suction elements is set to form liquid film；With
Step b：The suction elements that liquid film is formed using bottom draw particulate, the particulate is maintained at the absorption
The bottom of part simultaneously contacts with the liquid film.
2. particulate control method according to claim 1, it is characterised in that in the step a, by using the suction
Part is taken to draw liquid in advance to make the bottom of the suction elements form liquid film.
3. particulate control method according to claim 2, it is characterised in that in the step a, the suction elements are pre-
The liquid first drawn is the liquid for submerging the particulate.
4. particulate control method according to claim 1, it is characterised in that in the step b, utilize the drawing section
The particulate is drawn to after the bottom of the suction elements by part, stops sucking action, makes the particulate in negative pressure and described
The bottom of the suction elements is maintained in the presence of the tension force of liquid film.
5. particulate control method according to claim 1, it is characterised in that in the step b, using one or at least
The suction elements that two bottoms form liquid film draw particulate, and each suction elements only draw the single particulate.
6. particulate control method according to claim 1, it is characterised in that the particulate control method also includes being arranged at
Step c after the step b：The suction elements are moved to the top of the setting placement location of the particulate, and utilized
The suction elements drive the particulate to depart from the bottom of the suction elements and be placed on the setting placement location.
7. particulate control method according to claim 6, it is characterised in that in the step c, move down the suction
Take part, make the particulate directly with it is described setting placement location contact, make the particulate with it is described setting placement location it
Between adhesion and self gravitation in the presence of depart from the suction elements bottom, and be placed on it is described setting place position
Put.
8. particulate control method according to claim 6, it is characterised in that in the step c, utilize the drawing section
Part is sprayed the particulate, the particulate is departed from the lower end of the suction elements in the presence of malleation and self gravitation
Portion, and it is placed on the setting placement location.
9. particulate control method according to claim 6, it is characterised in that the particulate is placed on by the suction elements
During the setting placement location, the still remaining liquid for thering is part to draw in advance in the suction elements.
10. particulate control method according to claim 9, it is characterised in that the particulate control method also includes setting
Step d after the step c：The remaining liquid drawn in advance in the suction elements is discharged.
11. according to any described particulate control methods of claim 1-10, it is characterised in that the particle diameter of the particulate is 0.5-
3mm。
12. according to any described particulate control methods of claim 1-10, it is characterised in that the particulate is can be in nature
The gel state particulate of its own structural stability is maintained under state.
13. particulate control method according to claim 12, it is characterised in that the particulate is biological brick (20).
A kind of 14. biometric print method, it is characterised in that manipulated using any described particulate control methods of claim 1-13
Biological brick (20) as the particulate.
15. a kind of biological construct, it is characterised in that the biological construct utilizes the biometric print side described in claim 14
It is prepared by method.
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| CN107418998B (en) | 2020-02-28 |
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