CN1175635A - Air lift internal cross-current type bio-reactor - Google Patents

Air lift internal cross-current type bio-reactor Download PDF

Info

Publication number
CN1175635A
CN1175635A CN 96109551 CN96109551A CN1175635A CN 1175635 A CN1175635 A CN 1175635A CN 96109551 CN96109551 CN 96109551 CN 96109551 A CN96109551 A CN 96109551A CN 1175635 A CN1175635 A CN 1175635A
Authority
CN
China
Prior art keywords
reactor
shell
riser tube
nozzle
air lift
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.)
Granted
Application number
CN 96109551
Other languages
Chinese (zh)
Other versions
CN1049008C (en
Inventor
刘大陆
查丽杭
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute of Process Engineering of CAS
Original Assignee
Institute of Chemical Metallurgy CAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Institute of Chemical Metallurgy CAS filed Critical Institute of Chemical Metallurgy CAS
Priority to CN96109551A priority Critical patent/CN1049008C/en
Publication of CN1175635A publication Critical patent/CN1175635A/en
Application granted granted Critical
Publication of CN1049008C publication Critical patent/CN1049008C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/04Filters; Permeable or porous membranes or plates, e.g. dialysis
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/06Nozzles; Sprayers; Spargers; Diffusers
    • C12M29/08Air lift

Landscapes

  • Wood Science & Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

A bioreactor especially suitable for bioreaction process such as plant cell culture is composed of a casing, cylindrical lifting tube with more rows of holes at upper part and coaxially arranged in the casing, compound sieve plate filter positioned at join of the casing with liquid drainage chamber, and two air distributors over the filter and spraying air upward and downward respectively. Said bioreactor can suppress the gathering of air bubbles, inhibit the blow up of bubble on liquid surface, increasing the air content in liquid lowering area and intensifying transfer rate. Its advantages are greatly reduced height, filtering and washing at the same time, simple structure, and not polluting easily.

Description

Air lift internal cross-current type bio-reactor
The present invention relates to a kind of air lift type internal circulation biological reactor, particularly a kind of air lift internal cross-current type (Alicrof is Air lift lnternal Cross Flow) bio-reactor.Be applicable to the growth of cell and produce cultivation that be particularly useful for the shearing force sensitivity, culture cycle is long, easily pollutes, and bears the cultivation of the weak vegetable cell of bubble impact and bursting force effect.
At present generally believe that both at home and abroad airlift reactor is the widely applicable bio-reactor of a class.The structure of this class reactor is a bubbling pillar barrel shrond by the outside, adorns a baffle plate or cylinder riser tube in the barrel shrond, promptly by center riser tube, downtake, top gas-liquid separation chamber with rise downtake and constitute in the UNICOM chamber of bottom etc.Adorn a nozzle in the riser tube bottom, pressurized air is fed by nozzle, by compressed-air actuated kinetic energy, in fluid system, cause density difference, fluid is risen by riser tube, after gas-liquid separation chamber, descend by downtake, enter the riser tube bottom again, thereby form the process that circulates of fluid system.Riser tube has two kinds of single cylindrical duct and multistage cylindrical duct.But the main drawback of traditional airlift reactor is the height that it has emphasized reactor with not enough, has promptly designed big aspect ratio, thereby it is low or fall the deficient oxygen in liquid zone to fall the gas holdup of liquid zone; In long riser tube, cause bubbling polymerization again, grow up, when the liquid level explosion, produce the destructive force of pair cell.
Purpose of the present invention is the improvement to traditional airlift reactor, be again physico-chemical property characteristics at the lithospermum euchromum Royle cell, the requirement of culture cycle length and metabolic process, and the low ratio of height to diameter of designing, radially cross-flow, multi-use, air lift internal cross-current type bio-reactor simple in structure, this reactor adapted culture plant cell can obtain qualified secondary metabolite.
In air lift internal cross-current type bio-reactor provided by the invention, can wash, filter, change technological operations such as liquid, thereby in this bio-reactor, can carry out the growth and two step of production culturing process of cell continuously; , substratum long for culture cycle evaporates the bioprocesses of minimizing with the cultivation process, in this reactor, need not replenish or fed-batch medium, still can normal running.
Air lift internal cross-current type bio-reactor provided by the invention comprises cylinder barrel shaped shell (11), inverted cone cylindrical outer casing (9), cylinder barrel shaped discharge opeing chamber (5) and top gas-liquid separation chamber (24), riser tube (10), gas distributor (1), (2), strainer (7) etc.Gas separation chamber (24) be positioned at shell (11) above, be shell (9) below the shell (11), be discharge opeing chamber (5), their bottom connections in twos below again, co-axial with it riser tube (10), shell (9) and joint, discharge opeing chamber (5) are installed in the shell (11) lay strainer (7), in shell (9), gas distributor (1), (2) are installed in the top of strainer (7), and reactor head and bottom can be adopted flat or the dome-shaped end socket.
Riser tube (10) has the cylinder of many rounds for top, every adjacent two rounds are triangularly arranged, adjacent two round area sums equate with the basal area of riser tube or are close, its perforate segment length is 4/5~1/2 of a riser tube total height, riser tube is installed on the bearing rib (20) that is positioned at shell (11) and (9) joint by coaxial manner, on the section of riser tube two ends certain distance, each installs three reference columns (19) that equal length is uniform, with keep between the same shell (11) wait ring spacing from.
Gas distributor is that (1), (2) are two groups of combined nozzle spargers, constitute by ring pipe (23) and the built up nozzle (3) that is positioned on the ring pipe, nozzle (3) is made up of bearing and shower nozzle, shower nozzle end face and side have the pore less than 0.5 millimeter, nozzle on the gas distributor (1) is positioned at riser tube (10) annular zone, and is upwards jet, and the nozzle on the gas distributor (2) is jet downwards, make the inner material of inverted cone cylindrical outer casing (9) be in fluidization, no dead band exists.
Strainer (7) is the compound sieve plate type filter, and, porosity relative by two apertures formed greater than 20% porous plate, between two orifice plates stainless (steel) wire is housed, and the stainless (steel) wire aperture is between 40 orders~180 orders.
When reactor provided by the invention is placed on outdoor or do not have in the environment of temperature control condition, need round shape temperature control chuck (12) be installed in shell of reactor (11) outside.
Specifically describe the present invention below in conjunction with accompanying drawing, embodiment.
Fig. 1 is the structural representation of air lift internal cross-current type bio-reactor of the present invention.
Fig. 2 is the sectional view of Fig. 1 along the A-A direction.
Wherein:
(1)-gas distributor (2)-gas distributor (3)-nozzle
(4)-pipeline (5)-discharge opeing chamber (6)-liquid discharge pipe
(7)-strainer (8)-drainage conduit (9)-shell
(10)-riser tube (11)-shell (12)-temperature control chuck
(13)-aperture area (14)-gas-liquid separation zone (15)-fall liquid zone
(16)-dissolved oxygen gaging hole (17)-inoculated tube (18)-pH value gaging hole
(19)-reference column (20)-bearing rib (21)-water inlet
(22)-water outlet (23)-ring pipe (24)-gas-liquid separation chamber
As shown in Figure 1, 2, the composition of the air lift internal cross-current type bio-reactor that provides of the present invention and embodiment comprises cylinder barrel shaped shell (11), inverted cone cylindrical outer casing (9), cylinder barrel shaped discharge opeing chamber (5) and top gas-liquid separation chamber (24), riser tube (10), gas distributor (1), (2), strainer (7) etc.Gas separation chamber (24) be positioned at shell (11) above, be shell (9) below the shell (11), be discharge opeing chamber (5) below again, they are bottom connection in twos, co-axial with it riser tube (10) is installed in the shell (11), strainer (7) is laid in shell (9) and joint, discharge opeing chamber (5), gas distributor (1), (2) are installed in top at shell (9) internal filter (7), and dome-shaped end socket (also can adopt flat end socket) is adopted in reactor head and bottom.
Shell (11) and shell (9) joint are equipped with bearing rib (20), and bearing rib (20) is gone up vertical fixing riser tube (10) is installed in shell (11), and riser tube (10) and shell (11) are coaxial.
Riser tube (10) top has many rounds, every adjacent two rounds are triangularly arranged, adjacent two round area sums equate with the basal area of riser tube or are close, its perforate segment length is 4/5~1/2 of a riser tube total height, riser tube (10) is installed on the bearing rib (20) that is positioned at shell (11), (9) joint by coaxial manner, on the section of riser tube (10) two ends certain distance, each installs three reference columns (19) that equal length is uniform, with keep waiting between the same shell of riser tube (11) ring spacing from.
Strainer (7) is compound sieve-board type strainer, and is relative by two apertures, and porosity is formed greater than 20% porous plate, between two orifice plates stainless (steel) wire is housed, and the stainless (steel) wire aperture is between 40 orders~180 orders.
The gas distributor that the present invention uses (1), (2) are two groups of combined nozzle spargers, constitute by ring pipe (23) and the nozzle (3) that is fixed on the ring pipe, nozzle is made up of bearing and shower nozzle, shower nozzle end face and side have the pore less than 0.5 millimeter, nozzle (3) on the gas distributor (1) is positioned at riser tube (10) annular zone, upwards jet, the nozzle (3) on the gas distributor (2) is jet downwards, makes the inner material of inverted cone tube shell (9) be in fluidization.Gas separation chamber (24) upper end has dissolved oxygen gaging hole and pH value gaging hole.
The reactor that present embodiment provides has been installed round shape temperature control folder in shell (11) outside and has been overstated (12).
Material therefor of the present invention is stainless steel.
The concrete working process of air lift internal cross-current type reactor provided by the invention is as follows:
Steam enters in the reactor from discharge opeing chamber, bottom (5) through pipeline (4), is discharged by inoculated tube valve (17), finishes the disinfecting steps of reactor by the disinfecting action rules.Vapour condensation water is discharged through liquid discharge pipe (6).The suspended culture cell strain with substratum together in inoculated tube (17) adds shell (11), filtered air is by built up nozzle (1), (2) feed, nozzle (1) on the sparger (1) is positioned at riser tube (10) annular zone, upwards jet, cause density difference, make substratum, cell strain, the bubble three-phase fluid enters riser tube (10), upwards promote along (F), after fluid rises to the aperture area (13) of riser tube (10), to around enter to the shunting (cross-flow) of successively decreasing through bore open and to fall liquid zone (15), rise to the fluid at riser tube (10) top, also enter through gas-liquid separation zone (14) and fall liquid zone (15), the air that the nozzle (3) on sparger (2) feeds sprays downwards, make along the gas-liquid-solid three-phase fluid that falls liquid zone (15) decline in shell (9), to be fluidized state, can eliminate the dead band.Need the metathetical substratum to enter discharge opeing chamber (5), discharge by liquid discharge pipe (6) by assembled filter (7).Cultured products is discharged by blow-off valve (8), carries out the extraction separation aftertreatment.Carry out temperature controlled bioprocesses for needs, can be undertaken by the temperature of control water inlet (21) and water outlet (22).
The present invention has the following advantages and good effect:
(1) the present invention is owing to adopted the riser of top perforate, thereby be applicable to that cultivation cycle is long, culture medium evaporates the bioprocesses of minimizing with the cultivation process, in this reactor, need not to replenish or fed-batch medium, still can normal operating.
(2) the present invention is owing to adopted this Novel hoisting pipe, shunted by the cross-flow of radially successively decreasing around the middle mind-set in aperture area through the fluid that riser rises, changed the direction of fluid, slowed down the upper punch speed of fluid, thereby can suppress bubbling polymerization, prevent bubble when the liquid level explosion, to produce impulsive force to the damage of cell.
(3) the present invention is owing to adopted new gas distributor and riser, and the synergy of two parts, eliminated and fallen the deficient oxygen phenomenon in liquid zone, improved and fallen the liquid zone gas holdup, strengthen mixing and transfer rate, greatly reduced height for reactor.
(4) the present invention has adopted conical shell owing to the bottom, thereby applicable to the wide cell mass of particle diameter distribution, taper bed inner cell is in fluidization, and no dead band exists.
(5) in reactor of the present invention, can filter, wash, change the operations such as liquid, multi-use.
(6) reactor machinery-free drive disk assembly of the present invention, shearing force is little, and is simple in structure, easy to operate, is difficult for polluting, and amplifies easily.
Reactor of the present invention has built up 7 liters, 30 liters, 150 liters reactor series plant cell pilot scale culturing engineerings. The lithospermum euchromum Royle cellular entities of criticizing through 16 tanks is cultivated, and cell yield reaches 12 grams and rises dry weight/day, and shikonin content reaches as high as 22% of dry cell weight, is 10 times of the 5-of content in the natural plant.

Claims (6)

1, a kind of air lift internal cross-current type bio-reactor comprises housing, riser tube, it is characterized in that also comprising strainer and gas distributor etc.
Described housing is made up of cylinder barrel shaped shell (11), inverted cone cylindrical outer casing (9), cylinder barrel shaped discharge opeing chamber (5) and top gas-liquid separation chamber (24), gas-liquid separation chamber (24) be positioned at shell (11) above, below the shell (11) shell (9), again discharge opeing chamber (5), they are bottom connection in twos, and reactor head and bottom can be adopted flat or the dome-shaped end socket;
In shell (11) inside, place co-axial with it riser tube (10), provide pipe (10) to have the cylinder of many rounds for top;
Strainer (7) is the compound sieve plate type filter, is positioned at shell (9) and joint, discharge opeing chamber (5);
In shell (9), strainer (7) top is equipped with gas distributor (1), (2), gas distributor (1), (2) are two groups of combined nozzle spargers, constitute by the built up nozzle (3) on ring pipe (23) and the ring pipe, nozzle (3) on the gas distributor (1) is upwards jet, and the nozzle (3) on the gas distributor (2) is jet downwards;
2, by the described air lift internal cross-current type bio-reactor of claim 1, the many rounds that it is characterized in that described riser tube (10) top, every adjacent two rows are triangularly arranged, two round area sums equate with the basal area of riser tube (10) or are close that its perforate segment length is 1/2~4/5 of riser tube (a 10) total height; Riser tube (10) is installed on the bearing rib (20) that is positioned between housing (11), (9) by coaxial manner.
3, by the described air lift internal cross-current type bio-reactor of claim 1, it is characterized in that on the section of riser tube (10) two ends certain distance that each installs 3 reference columns (19) that length is uniform.
4, by the described air lift internal cross-current type bio-reactor of claim 1, it is characterized in that the nozzle (3) on described gas distributor (1), (2) is made up of bearing and shower nozzle, shower nozzle end face and side have the pore less than 0.5 millimeter, and the nozzle (3) on the gas distributor (1) is positioned at the annular zone of riser tube (10).
5, by the described air lift internal cross-current bio-reactor of claim 1, it is characterized in that described strainer (7) is relative by two apertures, porosity is formed greater than 20% porous plate, and stainless net is housed between two porous plates, and screen distance is between 40 orders~180 orders.
6,, it is characterized in that outside the described housing (11) round shape temperature control chuck (12) being installed by the described air lift internal cross-current type bio-reactor of claim 1.
CN96109551A 1996-08-29 1996-08-29 Air lift internal cross-current type bio-reactor Expired - Fee Related CN1049008C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN96109551A CN1049008C (en) 1996-08-29 1996-08-29 Air lift internal cross-current type bio-reactor

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN96109551A CN1049008C (en) 1996-08-29 1996-08-29 Air lift internal cross-current type bio-reactor

Publications (2)

Publication Number Publication Date
CN1175635A true CN1175635A (en) 1998-03-11
CN1049008C CN1049008C (en) 2000-02-02

Family

ID=5120433

Family Applications (1)

Application Number Title Priority Date Filing Date
CN96109551A Expired - Fee Related CN1049008C (en) 1996-08-29 1996-08-29 Air lift internal cross-current type bio-reactor

Country Status (1)

Country Link
CN (1) CN1049008C (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1292827C (en) * 2004-01-12 2007-01-03 石油大学(北京) Gas-liquid-solid composite reactor apparatus
CN100396624C (en) * 2003-12-11 2008-06-25 林德-Kca-德累斯顿有限公司 Process and device for biological treatment of a suspension in a bioreactor with integrated hydraulic bottom layer removal
CN102783414A (en) * 2011-05-19 2012-11-21 河南省海乐森药用细胞工程技术有限公司 External circulation mist-type bioreactor for large-scale cultivation of plant hairy roots
WO2017068265A1 (en) * 2015-10-23 2017-04-27 Gg Coriolis Liquid-medium digester with gas-flow-based agitation, comprising an automatic device for establishing a fluid communication between the upflow and downflow spaces according to the height of the medium
CN111635861A (en) * 2020-06-30 2020-09-08 江南大学 Airlift reactor for animal cell culture
CN117187030A (en) * 2023-11-06 2023-12-08 万华化学集团股份有限公司 Fermentation reaction kettle, corresponding fermentation system and application thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018094224A1 (en) * 2016-11-21 2018-05-24 Mih Water Treatment, Inc. Biochemical reactor
US11299700B1 (en) 2021-02-19 2022-04-12 Acequia Biotechnology, Llc Bioreactor containers and methods of growing hairy roots using the same

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8515629D0 (en) * 1985-06-20 1985-07-24 Celltech Ltd Fermenter
CN85109440A (en) * 1985-12-23 1987-07-08 无锡轻工业学院 The solution-air circulation bioreactor
ES2045379T3 (en) * 1988-01-20 1994-01-16 Pacques Bv PROCEDURE TO REDUCE THE EFFECT OF HYSTERESIS IN A CIRCUIT REACTOR WITH GAS SURVEY AND WITH SUSPENDED SOLID PARTICLES.
CN2033011U (en) * 1988-05-02 1989-02-22 天津大学 Fixed biotic catalyzer reactor
CN2078322U (en) * 1990-12-13 1991-06-05 中国科学院化工冶金研究所 Air-lift biological reactor for high-visco sity fermentation

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100396624C (en) * 2003-12-11 2008-06-25 林德-Kca-德累斯顿有限公司 Process and device for biological treatment of a suspension in a bioreactor with integrated hydraulic bottom layer removal
CN1292827C (en) * 2004-01-12 2007-01-03 石油大学(北京) Gas-liquid-solid composite reactor apparatus
CN102783414A (en) * 2011-05-19 2012-11-21 河南省海乐森药用细胞工程技术有限公司 External circulation mist-type bioreactor for large-scale cultivation of plant hairy roots
WO2017068265A1 (en) * 2015-10-23 2017-04-27 Gg Coriolis Liquid-medium digester with gas-flow-based agitation, comprising an automatic device for establishing a fluid communication between the upflow and downflow spaces according to the height of the medium
FR3042795A1 (en) * 2015-10-23 2017-04-28 Gg Coriolis CLOSER FOR LIQUID ENVIRONMENT WITH AUTOMATIC FLUID COMMUNICATION BETWEEN ASCENDING AND DESCENDING CIRCULATIONS IN RELATION TO THE LEVEL OF THE LIQUID ENVIRONMENT
US10975347B2 (en) 2015-10-23 2021-04-13 Biorea Fermenter for a liquid medium with gas circulation stirring, comprising an automatic device for establishing a fluid communication between the ascending circulation and the descending circulation volumes depending on the height of the medium
CN111635861A (en) * 2020-06-30 2020-09-08 江南大学 Airlift reactor for animal cell culture
CN117187030A (en) * 2023-11-06 2023-12-08 万华化学集团股份有限公司 Fermentation reaction kettle, corresponding fermentation system and application thereof
CN117187030B (en) * 2023-11-06 2024-02-27 万华化学集团股份有限公司 Fermentation reaction kettle, corresponding fermentation system and application thereof

Also Published As

Publication number Publication date
CN1049008C (en) 2000-02-02

Similar Documents

Publication Publication Date Title
US4978616A (en) Fluidized cell cultivation process
US4413058A (en) Continuous production of ethanol by use of flocculent zymomonas mobilis
CN1049008C (en) Air lift internal cross-current type bio-reactor
GB2073243A (en) Continuous fermentor or reactor
CN111135778A (en) Strong mixing reactor
CN106635797A (en) Bioreactor
CA1052715A (en) Introduction of nutrient medium into a fermenter
CN1019794B (en) Improved bed process
CN2270733Y (en) Internal alternate air flow type biological reactor
CN102336849B (en) Olefin polymerization reactor
CN212492861U (en) Strong mixing reactor
CN100397980C (en) Airlift biological reactor for culturing non-fixed roots of Danshen
CN1025491C (en) Improved fluidized bed process and apparatus
CN1605385A (en) Annular space gas lifting type loop reactor
CN1254531C (en) Air lift plant cell culture biological reactor with screen mesh guiding drum
CN210215327U (en) Device for preparing ethanol by fermentation of immobilized yeast
CN2078322U (en) Air-lift biological reactor for high-visco sity fermentation
CN1171990C (en) Gas-lifting recirculating reactor with more concentric guide barrels
CN211832184U (en) Edible mushroom liquid strain air-lift fermentation device
CN221117422U (en) Plant cell or tissue culture photoreactor
CN219384896U (en) External mud-water separation formula anaerobic reactor of abnormal flow
CN201031172Y (en) Tubes type biological fluidization reactor
CN1256180C (en) Split type adjustable quasi-fluidized bed reactor
CN216274173U (en) Oxygenation and mixing device of low-shear-force airlift fermentation tank
CN217972651U (en) Low-pressure efficient gas dissolving device

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee