RU2002130577A - METHOD FOR OPERATION, ANALYSIS AND BIOLOGICAL EVALUATION OF EMBRYOS AND / OR OVOSITES IN A MICROFLUIDAL CHANNEL AND DEVICE FOR ITS IMPLEMENTATION - Google Patents

METHOD FOR OPERATION, ANALYSIS AND BIOLOGICAL EVALUATION OF EMBRYOS AND / OR OVOSITES IN A MICROFLUIDAL CHANNEL AND DEVICE FOR ITS IMPLEMENTATION Download PDF

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RU2002130577A
RU2002130577A RU2002130577/15A RU2002130577A RU2002130577A RU 2002130577 A RU2002130577 A RU 2002130577A RU 2002130577/15 A RU2002130577/15 A RU 2002130577/15A RU 2002130577 A RU2002130577 A RU 2002130577A RU 2002130577 A RU2002130577 A RU 2002130577A
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embryo
fluid
channel
microfluidic
embryos
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RU2002130577/15A
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Дэвид Джей БИИБ (US)
Дэвид Джей БИИБ
Ян К. ГЛАЗГОВ (US)
Ян К. ГЛАЗГОВ
Мэтью Б. УИЛЕР (US)
Мэтью Б. УИЛЕР
Генри ЗЕРИНГ (US)
Генри ЗЕРИНГ
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Попечительский Совет Университета Штата Иллинойс (Us)
Попечительский Совет Университета Штата Иллинойс
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Priority claimed from US09/570,483 external-priority patent/US6695765B1/en
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Publication of RU2002130577A publication Critical patent/RU2002130577A/en

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    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502776—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for focusing or laminating flows
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
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    • 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
    • C12M21/00—Bioreactors or fermenters specially adapted for specific uses
    • C12M21/06—Bioreactors or fermenters specially adapted for specific uses for in vitro fertilization
    • 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
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/16—Microfluidic devices; Capillary tubes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0636—Focussing flows, e.g. to laminate flows
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668—Trapping microscopic beads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0418—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic electro-osmotic flow [EOF]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions

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Claims (15)

1. Способ анализа и биологической оценки эмбрионов и/или овоцитов в микрофлюидальном канале, включающий стадии: размещение эмбриона в флюидальном канале, размеры которого учитывают размеры эмбриона; создание потока жидкости в флюидальном канале; и оценка характеристик эмбриона в процессе его развития.1. The method of analysis and biological evaluation of embryos and / or oocytes in the microfluidic canal, comprising the steps of: placing the embryo in the fluid canal, the dimensions of which take into account the size of the embryo; creating a fluid flow in the fluid channel; and assessment of the characteristics of the embryo during its development. 2. Способ по п.1, отличающийся тем, что на указанной стадии создания потока жидкости перемещают эмбрион в флюидальный канал, а указанная стадия оценки характеристик эмбриона включает измерение скорости, с которой эмбрион перемещается в флюидальном канале.2. The method according to claim 1, characterized in that at the indicated stage of creating a fluid flow, the embryo is moved into the fluid channel, and said stage of evaluating the characteristics of the embryo includes measuring the speed at which the embryo moves in the fluid channel. 3. Способ по п.1, отличающийся тем, что на указанной стадии создания потока жидкости эмбрион перемещают в флюидальный канал, а указанная стадия оценки характеристик эмбриона включает измерение расстояния, на которое эмбрион перемещается в флюидальном канале.3. The method according to claim 1, characterized in that at the indicated stage of creating a fluid flow, the embryo is moved into the fluid channel, and said stage of evaluating the characteristics of the embryo includes measuring the distance over which the embryo moves in the fluid channel. 4. Способ по п.1, отличающийся тем, что указанная стадия оценки включает получение образца жидкости из участка микрофлюидального канала, расположенного ниже эмбриона, и проведение химического анализа образца жидкости.4. The method according to claim 1, characterized in that said evaluation step involves obtaining a fluid sample from a portion of the microfluidic channel located below the embryo and conducting a chemical analysis of the fluid sample. 5. Способ по п.1, отличающийся тем, что в микрофлюидальльном канале выполняют сужение, размер которого обеспечивает деформацию эмбриона в течение указанной стадии оценки, при этом оценивают возможность эмбриона к восстановлению его формы после прохождения через сужение.5. The method according to claim 1, characterized in that in the microfluidal canal a constriction is performed, the size of which ensures the deformation of the embryo during the indicated stage of assessment, while assessing the possibility of the embryo to restore its shape after passing through the narrowing. 6. Способ по п.1, отличающийся тем, что в микрофлюидальном канале выполняют сужение, размер которого предотвращает свободный проход эмбриона через сужение, при этом на указанной стадии создают поток жидкости для перемещения эмбриона в сужение для дальнейшей легкой его деформации давлением жидкости в течение короткого периода времени, а указанная стадия оценки определяет возможность эмбриона восстанавливать свою форму после деформации в течение короткого периода времени.6. The method according to claim 1, characterized in that the constriction is performed in the microfluidic channel, the size of which prevents the embryo from freely passing through the constriction, while at this stage a fluid flow is created to move the embryo into the constriction for its further easy deformation by liquid pressure for a short time period, and the specified stage of assessment determines the ability of the embryo to restore its shape after deformation in a short period of time. 7. Способ оперирования или обработки эмбрионов, включающий стадии размещение эмбриона в микрофлюидальном канале, размеры которого учитывают размеры эмбриона; создание потока жидкости в микрофлюидальном канале; и обработка эмбриона для изменения его характеристик во время его позиционирования в микрофлюидальном канале.7. A method for operating or processing embryos, comprising the steps of placing an embryo in a microfluidic channel, the dimensions of which take into account the size of the embryo; creating a fluid flow in the microfluidic channel; and processing the embryo to change its characteristics during its positioning in the microfluidic channel. 8. Способ по п.7, отличающийся тем, что в микрофлюидальльном канале выполняют ряд сужений и выступы, имеющие постепенно сокращающееся пространство между ними, а указанная стадия обработки включает управление потоком жидкости в микрофлюидальном канале, чтобы переместить эмбрион по крайней мере через одно из сужений и отделить кумулюс.8. The method according to claim 7, characterized in that in the microfluidal canal a series of contractions and protrusions are performed, which have a gradually decreasing space between them, and said processing step includes controlling the flow of fluid in the microfluidic canal to move the embryo through at least one of the constrictions and separate the cumulus. 9. Способ по п.8, отличающийся тем, что размер одного из последних рядов сужений в упомянутом ряде сужений выполняют таким образом, чтобы блокировать проход эмбриона, а указанная стадия обработки включает управление потоком жидкости в микрофлюидальном канале, чтобы провести эмбрион через другие ряды сужений, а затем при управлении потоком жидкости высосать кумулюс, когда эмбрион позиционирован в последнем ряде сужений.9. The method according to claim 8, characterized in that the size of one of the last rows of constrictions in the mentioned series of constrictions is performed in such a way as to block the passage of the embryo, and the specified processing stage includes controlling the flow of fluid in the microfluidic channel to guide the embryo through other rows of constrictions and then, when controlling the fluid flow, suck out the cumulus when the embryo is positioned in the last row of constrictions. 10. Способ по п.7, отличающийся тем, что микрофлюидальный канал включает сужение такого размера, чтобы блокировать проход эмбриона, указанная стадия обработки включает изменение состава жидкости в флюидальном канале путем пропускания над эмбрионом кислотного раствора, при этом эмбрион позиционирован в сужении для отделения оволеммы.10. The method according to claim 7, characterized in that the microfluidic channel includes a restriction of such a size as to block the passage of the embryo, said processing step involves changing the composition of the liquid in the fluid channel by passing an acid solution over the embryo, while the embryo is positioned in the constriction to separate the ovolemma . 11. Способ по п.10, отличающийся тем, что указанную стадию обработки используют для формирования химеры путем изменения состава жидкости в флюидальном канале путем введения кислотного раствора и пропускания указанного кислотного раствора над двумя эмбрионами, позиционированными в сужении, для отделения оволеммы, а затем изменяют состав жидкости в флюидальном канале для стимуляции культивирования химеры, образованной от этих двух эмбрионов.11. The method according to claim 10, characterized in that the said processing step is used to form a chimera by changing the composition of the liquid in the fluid channel by introducing an acid solution and passing the specified acid solution over two embryos positioned in the narrowing to separate the ovolemma, and then change fluid composition in the fluid channel to stimulate the cultivation of a chimera formed from these two embryos. 12. Микрофлюидальное устройство для оперирования эмбрионами, включающее сеть транспортировки эмбрионов (32, 50) с наличием биологической среды для перемещения помещенных в сеть эмбрионов, в указанной сети транспортировки выполнены флюидальный канал (14), размеры которого учитывают размеры эмбриона, и отверстия (36, 52) для подачи жидкости в сеть транспортировки.12. A microfluidic device for handling embryos, including an embryo transport network (32, 50) with a biological medium for moving the embryos placed on the network, a fluid channel (14) is made in the said transport network, the dimensions of which take into account the size of the embryo, and openings (36, 52) for supplying liquid to the transportation network. 13. Устройство по п.12, отличающееся тем, что дополнительно выполнено T-образное соединение (14b) в сети транспортировки, сформированное на пересечении двух флюидальных каналов, и второе отверстие для подачи жидкости на отдельный участок флюидального канала в сеть транспортировки.13. The device according to p. 12, characterized in that it further comprises a T-shaped connection (14b) in the transportation network, formed at the intersection of two fluid channels, and a second hole for supplying fluid to a separate section of the fluid channel in the transportation network. 14. Устройство по п.1, отличающееся тем, что дополнительно в указанном флюидальном канале (14) выполнена компартментная часть - карман (14а), сформированная таким образом, чтобы удержать эмбрион в течение периода протекания потока жидкости с заранее определенной скоростью потока и позволить эмбриону быть вынесенным из указанной компартментной части - кармана потоком жидкости, имеющим более низкую скорость.14. The device according to claim 1, characterized in that in addition to the specified fluid channel (14) there is a compartment - a pocket (14a) formed in such a way as to hold the embryo during the period of the fluid flow at a predetermined flow rate and allow the embryo be removed from the specified compartment — the pocket by a fluid stream having a lower speed. 15. Микрофлюидальное устройство для оплодотворения яйцеклетки, включающее сеть транспортировки яйцеклетки (32, 50) с наличием биологической среды для перемещения помещенной в нее яйцеклетки, в указанной сети транспортировки выполнен флюидальный канал (14), размеры которого учитывают размеры яйцеклетки, и отверстия (36, 52) для подачи жидкости в сеть транспортировки; и T-образное соединение (14b) в сети транспортировки, сформированное на пересечении двух микрофлюидальных каналов (14), и второе отверстие для подачи жидкости со сперматозоидами в сеть транспортировки на отдельном участке микрофлюидального канала.15. A microfluidic device for fertilizing an egg, including an egg transport network (32, 50) with a biological medium for moving an egg placed in it, a fluid channel (14) is made in this transport network, the dimensions of which take into account the size of the egg and holes (36, 52) for supplying liquid to the transportation network; and a T-shaped connection (14b) in the transportation network, formed at the intersection of two microfluidic channels (14), and a second hole for supplying sperm fluid to the transportation network in a separate section of the microfluidic channel.
RU2002130577/15A 2000-05-12 2001-05-08 METHOD FOR OPERATION, ANALYSIS AND BIOLOGICAL EVALUATION OF EMBRYOS AND / OR OVOSITES IN A MICROFLUIDAL CHANNEL AND DEVICE FOR ITS IMPLEMENTATION RU2002130577A (en)

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