CN109892292A - Drug delivery device and drug delivery method for screening drugs by using drosophila - Google Patents
Drug delivery device and drug delivery method for screening drugs by using drosophila Download PDFInfo
- Publication number
- CN109892292A CN109892292A CN201910235932.7A CN201910235932A CN109892292A CN 109892292 A CN109892292 A CN 109892292A CN 201910235932 A CN201910235932 A CN 201910235932A CN 109892292 A CN109892292 A CN 109892292A
- Authority
- CN
- China
- Prior art keywords
- container
- drug
- drosophila
- liquid food
- drug delivery
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention discloses a drug delivery device for screening drugs by using fruit flies, and belongs to the field of drug screening. The device comprises a container 1 with an opening at the upper part, a cover body 2 capable of covering the opening, a container 3 and a U-shaped capillary tube 4, wherein one end of the U-shaped capillary tube 4 penetrates through the cover body 2 and extends into the container 1, and the other end of the U-shaped capillary tube extends into the container 3. The invention also discloses a drug delivery method using the drug delivery device, when a certain amount of liquid food containing candidate drugs is filled in the container 3, the capillary can deliver the drug to the fruit flies in the container 1 through siphoning. The administration device has the advantages of simple structure, convenient use, easy operation and low cost, and can be used for researching various aspects of food and medicine consumption, energy metabolism, ingestion behavior and the like; meanwhile, the dressing change operation is convenient, the time consumption is short, and the screening can be carried out at high throughput.
Description
Technical field
Of the invention belongs to drug screening field, and in particular, to it is a kind of using drosophila screening drug drug delivery device and
Medication.
Background technique
Drosophila melanogaster (Drosophila melanogaster) is one of most important model organism in biological study,
Early in early 20th century, Morgan just selects Drosophila melanogaster as research object, has there is 100 years of researches history so far.State
Inside and outside numerous laboratories be all engaged in genetic development biology with drosophila in terms of work because it have other animals it is incomparable
Advantage, in addition to small in size, the service life is short, raising is easy, low in cost, the generation cycle is short, reproductive capacity is strong, filial generation quantity is more, deposits
It is small in phenotypic markers, the gene redundancy degree largely convenient for genetic manipulation, it is important that the study of human disease-related gene position more than 70%
Corresponding homologous gene can be all found in drosophila body, and there are the conservatives of height for the signal path of drosophila and the mankind, more
Research human diseases is used to come more transgenic drosophila models.
Research and development cost can be preferably reduced with the drug screening that drosophila carries out disease, is easily managed, is suitble to extensive medicine
Object screening.However, the foundation of medicine sorting platform and analysis method is perfect not enough, we need to establish more efficiently, it is simple,
It is convenient, it can be applied to the technology of large-scale medicine screening.Currently, domestic external application drosophila carries out the main side of large-scale medicine screening
Formula is that drug is dissolved in DMSO using 96 orifice plates, and yeast solids food is added and is administered, although this method has very greatly
Screening value, but there is also many deficiencies, such as are greatly limited by stability and solubility of the drug in food, and dressing is numerous
It is trivial, single hole screening animal numbers are limited etc..
Summary of the invention
In order to solve the above-mentioned technical problem, inventor pass through a large amount of creative work, from drug administration carrier, drug delivery device,
The stage constructions such as medication are studied, a kind of simpler, efficient, practical, safe, low-cost administration in final design
Mode, thereby completing the present invention.
An aspect of of the present present invention provides a kind of drug delivery device for using drosophila screening drug candidate, including top has
Open container 1 can cover lid 2, container 3 and the U-shaped capillary 4 closed in opening, and U-shaped 4 one end of capillary penetrates lid 2
It protrudes into container 1, the other end protrudes into container 3, wherein a certain amount of liquid containing drug candidate can be housed in the container 3
Food.
In the present invention, the container 1 can be made of any materials, and shape includes but is not limited to ampuliform, tubular, box
Shape.
In of the invention, the lid 2 of any materials by that can also be made, as long as the opening for closing container 1 can be covered.
Including but not limited to ground glass, rubber, cavernous body etc..When lid 2 is that hard material is made, need to prepare opening, so that
Capillary 4 can extend into container 1；When lid 2 be soft material for example cavernous body is made when, reserved opening, hair can not had to
Tubule 4 can penetrate lid 2 by external force.
In of the invention, the material of U-shaped capillary can also be made of any materials, such as the metals such as glass, stainless steel.
In some embodiments of the present invention, the U-shaped capillary be glass tube, outer diameter 1mm, internal diameter 0.8mm,
It is about 15cm, alcolhol burner excessive fire generation is U-shaped, and similar specification can also be customized through producer.It can also be more according to screening medication amount
It is few, 1-5 U-shaped glass tubes are placed in same container.
In some embodiments of the present invention, include containing about 200 μ L in the plastic tube that the U-shaped capillary 4 is connected
The liquid food of drug candidate, about for 20 drosophila feeding 7-10 days or so.After 7-10 days, new liquid food need to be only added
Object does not need provision for disengagement.
In some embodiments of the present invention, low concentration agar is contained in the bottom of the container 1.
The second aspect of the present invention provides a kind of medication using drosophila screening drug, comprising the following steps:
(1) drosophila liquid food is prepared；
(2) drug candidate and natural plant gum are milled and is dissolved in drosophila liquid food after mixing.
In some specific embodiments of the invention, edible pigment, such as edible pigment are contained in the liquid food
Brilliant blue (CAS:3844459).
In other specific embodiments of the invention, the content of edible pigment is 1% in the liquid food.
In some embodiments of the present invention, the natural plant gum is selected from Arabic gum, peach gum, pectin, apricot glue, alginic acid
At least one of.
In one embodiment of the invention, the natural plant gum is Arabic gum.
In some embodiments of the present invention, further comprise using drug delivery device described in first aspect present invention into
The step of row administration:
It will be transferred in container 1 after the anesthesia of a certain number of drosophilas, and got togather using the lid of lid 2；
The liquid food containing drug candidate is transferred in container 3,
One end of U-shaped capillary 4 is penetrated lid 2 to protrude into container 1, the other end, which protrudes into container 3, contains candidate medicine
In the liquid food of object；
It is 25 DEG C that drug delivery device, which is put into temperature, humidity 60%, is trained in the incubator of 12h/12h light and shade circulation
It supports.
The third aspect of the present invention provides a kind of drosophila liquid food containing the drug candidate using drosophila screening, special
Sign is, described its be dissolved in drosophila liquid food after the drug candidate and natural plant gum to be milled to mixing made of.
Natural plant gum packaging medicine is based on using two kinds of polymer, in different pH, the variation of charge (generates opposite electricity
Lotus) cause phase separation-coacervation, also referred to as complex coacervation.Such as with natural plant gum (negatively charged) and gelatin, (pH is in the above band of isoelectric point
It is negative electrical charge, positively charged below isoelectric point) make capsule material, drug is first mixed with Arabic gum or gelatin, be made suspension or
Emulsion wraps up drug.
In some embodiments of the present invention, the natural plant gum is selected from Arabic gum, peach gum, pectin, apricot glue, alginic acid
At least one of.
In one embodiment of the invention, the natural plant gum is Arabic gum.
In some embodiments of the present invention, the liquid food can be the common of known formulations and grow for drosophila
Liquid food.
In some specific embodiments of the invention, refer to containing edible pigment as food intake in the liquid food
Show agent, such as edible pigment brilliant blue (CAS:3844459).
Beneficial effects of the present invention
Drug delivery device of the invention compared with the existing technology, achieve it is following the utility model has the advantages that
One, in conjunction with CAFE (CApillary FEeder assay) (Ja, W.W., G.B.Carvalho, E.M.Mak,
N.N.de la Rosa,A.Y.Fang,J.C.Liong,T.Brummel,and S.Benzer.2007.'Prandiology of
Drosophila and the CAFE assay', Proc Natl Acad Sci U S A, 104:8253-56. pass through reference
It is incorporated by herein) technology, i.e. capillary administration, administration is micro, economical, can preferably reduce the dosage and dressing time of drug
Number can also quantify the food drug dose of drosophila intake.
Two, inventor improves existing CAFE technology, and structure is simple, easy to use, easily operated, at low cost
It is honest and clean, it can be used to study all various aspects such as consumption, energetic supersession, feeding behaviour of food drug；Dressing simultaneously is easy to operate, consumption
When it is short, can high throughput screened.
Three, bottom of device is covered with low concentration agar, is able to maintain that enough humidity in pipe, does not need additional moisturizing device.
Medication of the present invention is a kind of completely new medication, compared with the existing technology, achieve it is following the utility model has the advantages that
One, with Arabic gum packaging medicine, drug solubility and stability are greatly solved the problems, such as, expanded for
Drug range is screened, avoids organic solvent to the toxicity of drosophila, Arabic gum has slow release, biocompatibility, biology can
It is degradability, significant non-toxic nature, cheap, it is a kind of natural polysaccharide, has been widely used for food industries and pharmaceuticals industry
As wafer processed.
Two, yeast solids food is replaced using the liquid food that nutritional ingredient and content determine, is able to satisfy drosophila growth hair
Required nutrition is educated, ensure that the stability of food, while being suitable for long-term cultivation.
Three, drug is placed in the liquid food for being able to satisfy drosophila development by this method, can be used for common disease model
Drug screening, such as tumour, fat and other chronic diseases, such as aging and neurodegenerative disorders are these diseases
Drug research provides necessary technical support.
Four, it solves the drawbacks of current medication, improves operational efficiency.
Detailed description of the invention
Fig. 1 shows drug delivery device schematic diagram of the invention.
Schematic diagram is used Fig. 2 shows drug delivery device of the invention.
Specific embodiment
In order to which the technical problems, technical solutions and beneficial effects solved by the present invention is more clearly understood, below in conjunction with
Embodiment, the present invention will be described in further detail.
Embodiment
Following example is used herein to demonstration the preferred embodiments of the invention.Those skilled in the art, it will be appreciated that under
State the technology disclosed in example represent inventor discovery can be used for implementing technology of the invention, therefore can be considered as implementation this
The preferred embodiment of invention.But those skilled in the art should be understood that specific reality disclosed herein according to this specification
Many modifications can be made by applying example, still can be obtained identical or similar as a result, rather than away from the spirit or scope of the present invention.
Unless otherwise defined, the term of all technologies as used herein and science, and the technology in fields of the present invention
Personnel institute is normally understood equivalent in meaning, and being disclosed reference and their materials of reference will all be incorporated.
Those skilled in the art will recognize or just will appreciate that by routine test many described here
Invention specific embodiment many equivalent technologies.These will equally be comprised in claims.
Embodiment 1 screens the drug delivery device of drug using drosophila
This example provides a kind of drug delivery device for using drosophila screening drug candidate, as shown in Fig. 1, the device packet
It includes top to have open container 1, lid 2, container 3 and the U-shaped capillary 4 closed in opening can be covered, U-shaped capillary 4 one
End penetrates lid 2 and protrudes into container 1, and the other end protrudes into container 3.Wherein, container 1 is 50mL plastic tube, and lid 2 is sponge
Plug, container 3 are plastic centrifuge tube.
When use (Fig. 2), low concentration agar is arranged at 1 bottom of container, is then placed in appropriate drosophila, is equipped in container 3 containing time
The liquid food of drug is selected, container 1 and container 3 are constituted linker by siphonage by capillary, so as to in container 1
Drosophila be administered, can accomplish to continue uninterruptedly to be administered.When drug consumption is complete, it is only necessary to which supplement contains time in container 3
Select the liquid food of drug.
The utilization of 2 embodiment of embodiment, 1 drug delivery device
Reagent: liquid food is (with specific reference to Preparation of a holidic medium for Drosophila
Described by melanogaster article (Piper, M.D., E.Blanc, R.Leitao-Goncalves, M.Yang, X.He,
N.J.Linford,M.P.Hoddinott,C.Hopfen,G.A.Soultoukis,C.Niemeyer,F.Kerr,
S.D.Pletcher,C.Ribeiro,and L.Partridge.2014.'A holidic medium for Drosophila
Melanogaster', Nat Methods, 11:100-05. are incorporated to herein by reference of text), edible pigment (pigment brilliant blue
(CAS:3844459), agar (A800729；Mike woods Reagent Company)
(1) it assembles invention device: the agar solution of 2mL2% being added in the plastic tube of 50ml, it is soft beyond the Great Wall to its solidification
Matter sponge plug；
(2) the drosophila liquid food that nutritional ingredient and content determine is prepared, the edible pigment for being added 1% (is used to indicate fruit
Ingestion of medicines amount in fly body), it is uniformly mixed；
(3) drug and Arabic gum are milled mixing with miniature grinding rod, liquid food is added, it is equal to form quality for stirring
One suspension, is kept in dark place in plastic centrifuge tube；
(4) a certain number of experiment drosophilas (about 10-30 is only) is anaesthetized, is transferred in (1) in ready plastic bottle, to it
Recovery；
(5) plastic centrifuge tube of the drug containing liquid food in (3) is connected into U-shaped capillary glass tube, micro glass after about 1 minute
The glass capillary other end passes through beyond the Great Wall from the soft sponge of culture plastic bottle；U-shaped capillary is glass tube, outer diameter 1mm, internal diameter
For 0.8mm, it is about 15cm, alcolhol burner excessive fire generates U-shaped.
(6) above-mentioned apparatus is put into temperature is 25 DEG C, humidity 60%, is carried out in the incubator of 12h/12h light and shade circulation
Culture, and it is spaced dressing in 7 days or so.
3 case verification of embodiment
Below by taking drosophila intestinal canal tumour model as an example, with the invention antitumor medicine screening, demonstrating that the invention has can
Row and practical application value, concrete operations are as follows:
(1) intestinal cancer transgenic drosophila model is established: hsflp；FRT40A,tubGal80；tubGal4,UASGFP/TM3♀X
FRT40A,lgl-/-,UASRasV12/Cyo；F1 is as research object for TM3/TM6B ♂ filial generation；
(2) after the water-bath heat shock 1 hour of 37 DEG C of F1 drosophila, will be put into temperature is 25 DEG C, humidity 60%, 12h/12h light and shade
15d is cultivated in the incubator of circulation；
(3) by body formula light field microscope combination Stereo fluorescence microscope, flat wing is picked out, the female that blood-shot eye illness, GFP are expressed
Drosophila, using embodiment 2 method carry out drug screening, 15/pipe, and use anti-tumor drug methotrexate (MTX) (400 μM) as
5d is administered in positive control；
(4) drosophila enteron aisle is dissected, in fluorescence microscopy microscopic observation, by comparing GFP positive tumor stem cell clone number
And size, quantization screening drug；
The result shows that methotrexate (MTX) can actually effectively inhibit tumour, tumour is obviously reduced, demonstrate drug delivery device and
The practical application value of medication.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To make various changes or modifications to the present invention, such equivalent forms equally fall within model defined by the application the appended claims
It encloses.
Claims (10)
1. a kind of drug delivery device for using drosophila screening drug candidate, which is characterized in that the appearance including top with opening
Device (1) can cover lid (2), container (3) and the U-shaped capillary (4) closed in opening, and U-shaped capillary (4) one end penetrates lid
Body (2) protrudes into container (1), and the other end protrudes into container (3), wherein can contain candidate equipped with a certain amount of in the container (3)
The liquid food of drug.
2. drug delivery device according to claim 1, which is characterized in that the quantity of the U-shaped capillary (4) is multiple.
3. drug delivery device according to claim 1, which is characterized in that the lid (2) is soft cavernous body.
4. drug delivery device according to claim 1, which is characterized in that the container (3) can accommodate to be contained described at least 200 μ L
There is the liquid food of drug candidate.
5. drug delivery device according to claim 1 to 3, which is characterized in that contain low dense in the bottom of the container (1)
Spend agar.
6. a kind of medication using drosophila screening drug, which is characterized in that including preparing the liquid food containing drug candidate
The step of object:
(1) drosophila liquid food is prepared；
(2) drug candidate and natural plant gum are milled and is dissolved in drosophila liquid food after mixing.
7. medication according to claim 5, which is characterized in that the natural plant gum is selected from Arabic gum, peach gum, fruit
At least one of glue, apricot glue, alginic acid.
8. medication according to claim 6, which is characterized in that further comprise using it is described in claim 1 to
The step of medicine device is administered:
It will be transferred in container (1) after the anesthesia of a certain number of drosophilas, and got togather using lid (2) lid；
The liquid food containing drug candidate is transferred in container (3),
One end of U-shaped capillary (4) is penetrated lid (2) to protrude into container (1), the other end protrudes into containing in container (3) and waits
It selects in the liquid food of drug；
It is 25 DEG C that drug delivery device, which is put into temperature, humidity 60%, is cultivated in the incubator of 12h/12h light and shade circulation.
9. a kind of drosophila liquid food containing the drug candidate using drosophila screening, which is characterized in that described its is will be described
Made of drug candidate and natural plant gum are milled and are dissolved in drosophila liquid food after mixing.
10. drosophila liquid food according to claim 9, which is characterized in that the natural plant gum is selected from Arabic gum, peach
At least one of glue, pectin, apricot glue, alginic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910235932.7A CN109892292A (en) | 2019-03-27 | 2019-03-27 | Drug delivery device and drug delivery method for screening drugs by using drosophila |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910235932.7A CN109892292A (en) | 2019-03-27 | 2019-03-27 | Drug delivery device and drug delivery method for screening drugs by using drosophila |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109892292A true CN109892292A (en) | 2019-06-18 |
Family
ID=66953152
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910235932.7A Pending CN109892292A (en) | 2019-03-27 | 2019-03-27 | Drug delivery device and drug delivery method for screening drugs by using drosophila |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109892292A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20190364885A1 (en) * | 2017-01-16 | 2019-12-05 | Abgiome, Inc. | Methods and compositions for feeding piercing and sucking insects |
| CN110604823A (en) * | 2019-10-21 | 2019-12-24 | 兰州大学 | Method for rapidly screening anti-saccharification and/or anti-aging substances |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8608872D0 (en) * | 1985-04-11 | 1986-05-14 | Mini Agriculture & Fisheries | Controlling insects |
| CN1692717A (en) * | 2005-05-11 | 2005-11-09 | 北京卓凯生物技术有限公司 | Method and apparatus for application of chemicals to insect, and use for selecting medicine in large scale therewith |
| CN101427672A (en) * | 2008-12-16 | 2009-05-13 | 冯薇 | Aqueous suspension of phytocide sethoxydim and method of producing the same |
| CN102179219A (en) * | 2011-05-04 | 2011-09-14 | 金红叶纸业集团有限公司 | Method of preparing microcapsule emulsion with high-concentration and high core/wall ratio by adopting complex coacervation method |
| CN204762891U (en) * | 2015-06-01 | 2015-11-18 | 新疆农业大学 | Device is raised to trypetid class insect adult |
| CN207948637U (en) * | 2018-02-08 | 2018-10-12 | 四川农业大学 | The drosophila breeding apparatus that multicell combined type drosophila feed intake accurately measures |
-
2019
- 2019-03-27 CN CN201910235932.7A patent/CN109892292A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8608872D0 (en) * | 1985-04-11 | 1986-05-14 | Mini Agriculture & Fisheries | Controlling insects |
| CN1692717A (en) * | 2005-05-11 | 2005-11-09 | 北京卓凯生物技术有限公司 | Method and apparatus for application of chemicals to insect, and use for selecting medicine in large scale therewith |
| CN101427672A (en) * | 2008-12-16 | 2009-05-13 | 冯薇 | Aqueous suspension of phytocide sethoxydim and method of producing the same |
| CN102179219A (en) * | 2011-05-04 | 2011-09-14 | 金红叶纸业集团有限公司 | Method of preparing microcapsule emulsion with high-concentration and high core/wall ratio by adopting complex coacervation method |
| CN204762891U (en) * | 2015-06-01 | 2015-11-18 | 新疆农业大学 | Device is raised to trypetid class insect adult |
| CN207948637U (en) * | 2018-02-08 | 2018-10-12 | 四川农业大学 | The drosophila breeding apparatus that multicell combined type drosophila feed intake accurately measures |
Non-Patent Citations (6)
| Title |
|---|
| 史彭: "《物理实验》", 31 December 1993, 西安：西北工业大学出版社 * |
| 吴克刚等: "《食品微胶囊技术》", 31 July 2006, 北京：中国轻工业出版社 * |
| 宋健等: "《微胶囊化技术及应用》", 30 September 2001, 北京：化学工业出版社 * |
| 张峰等: "《细胞工程》", 31 July 2014, 北京：中国农业大学出版社 * |
| 方芳: "复凝聚法制备药物微胶囊及细胞毒性评价", 《实验室研究与探索》 * |
| 青少年科技活动大会编委会: "《青少年科技活动大全》", 31 March 1999, 上海：上海科技教育出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20190364885A1 (en) * | 2017-01-16 | 2019-12-05 | Abgiome, Inc. | Methods and compositions for feeding piercing and sucking insects |
| CN110604823A (en) * | 2019-10-21 | 2019-12-24 | 兰州大学 | Method for rapidly screening anti-saccharification and/or anti-aging substances |
| CN110604823B (en) * | 2019-10-21 | 2020-10-20 | 兰州大学 | Method for rapidly screening anti-saccharification and/or anti-aging substances |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Bergman et al. | Phycomyces | |
| Göpfrich et al. | One-pot assembly of complex giant unilamellar vesicle-based synthetic cells | |
| Albersheim et al. | Plant cell walls | |
| CN101460253B (en) | Method and apparatus for manipulating single cells and small aggregates thereof | |
| Roberts et al. | Dopamine secretion by PC12 cells microencapsulated in a hydroxyethyl methacrylate-methyl methacrylate copolymer | |
| CN102124096A (en) | Organ mimic device with microchannels and methods of use and manufacturing thereof | |
| CN109892292A (en) | Drug delivery device and drug delivery method for screening drugs by using drosophila | |
| Fang et al. | Enabling peristalsis of human colon tumor organoids on microfluidic chips | |
| CN110448696A (en) | Preparation method and application based on salt algae excretion body targeted delivery of drugs carrier | |
| CN102512458A (en) | Semi-bionic extraction method for active components of Cordyceps militaris | |
| Mooranian et al. | Influence of biotechnological processes, speed of formulation flow and cellular concurrent stream-integration on insulin production from β-cells as a result of co-encapsulation with a highly lipophilic bile acid | |
| CN107937328A (en) | Comparator and application and cytocomputer based on cell | |
| Hotos et al. | The effect of various salinities and light intensities on the growth performance of five locally isolated microalgae [Amphidinium carterae, Nephroselmis sp., Tetraselmis sp.(var. red pappas), Asteromonas gracilis and Dunaliella sp.] in laboratory batch cultures | |
| Pachiappan et al. | Isolation and culture of microalgae | |
| Schwarz et al. | Revisiting centrioles in nematodes—historic findings and current topics | |
| CN100446665C (en) | Indoor culture device of copepoda population | |
| Szypuła et al. | Huperzine A and huperzine B production by prothallus cultures of Huperzia selago (L.) Bernh. ex Schrank et Mart | |
| Tseng et al. | Electrospun polylactic acid (PLLA) microtube array membrane (MTAM)—An advanced substrate for anticancer drug screening | |
| Lee et al. | Rapid one‐step purification of single‐cells encapsulated in alginate microcapsules from oil to aqueous phase using a hydrophobic filter paper: Implications for single‐cell experiments | |
| Pardy | The morphology of green hydra endosymbionts as influenced by host strain and host environment | |
| CN107964530B (en) | Duckweed protoplast preparation method | |
| Ehret | Organelle Systems and Biological Organization: Structural and developmental evidence leads to a new look at our concepts of biological organization. | |
| CN106221887B (en) | A kind of method of the total rouge of high efficiency extraction ocean ballstone frustule | |
| CN100540647C (en) | Groove shape porous plate animal cell hollow fiber reactor and uses thereof | |
| Garcia-Parra et al. | Therapeutic potential of microalgae-derived bioactive metabolites is influenced by different large-scale culture strategies |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190618 |