Microreactor architecture and methods
First Claim
1. An apparatus, comprising:
- a chip comprising a predetermined reaction site having an inlet, an outlet, and a volume of less than about 1 ml, the predetermined reaction site constructed and arranged to maintain at least one living cell at the predetermined reaction site, wherein the chip is constructed and arranged to stably connect in a predetermined, aligned relationship to other, similar chips.
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Accused Products
Abstract
The present invention generally relates to chemical, biological, and/or biochemical reactor chips and other reaction systems such as microreactor systems, as well as systems and methods for constructing and using such devices. In one aspect, a chip or other reaction system may be constructed so as to promote cell growth within it. In certain embodiments, the chips or other reaction systems of the invention include one or more reaction sites. The reaction sites can be very small, for example, with a volume of less than about 1 ml. In one aspect of the invention, a chip is able to detect, measure and/or control an environmental factor such as the temperature, pressure, CO2 concentration, O2 concentration, relative humidity, pH, etc. associated with one or more reaction sites, by using one or more sensors, actuators, processors, and/or control systems. In another aspect, the present invention is directed to materials and systems having humidity and/or gas control, for example, for use with a chip. Such materials may have high oxygen permeability and/or low water vapor permeability. The present invention, in still another aspect, generally relates to light-interacting components suitable for use in chips and other reactor systems. These components may include waveguides, optical fibers, light sources, photodetectors, optical elements, and the like.
149 Citations
116 Claims
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1. An apparatus, comprising:
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a chip comprising a predetermined reaction site having an inlet, an outlet, and a volume of less than about 1 ml, the predetermined reaction site constructed and arranged to maintain at least one living cell at the predetermined reaction site, wherein the chip is constructed and arranged to stably connect in a predetermined, aligned relationship to other, similar chips. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
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9. An apparatus, comprising:
a chip comprising a predetermined reaction site having an inlet, an outlet, and a volume of less than about 1 ml, wherein the chip is constructed and arranged to be stably connectable to a microplate. - View Dependent Claims (10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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23. An apparatus, comprising:
a chip comprising a predetermined reaction site having an inlet, an outlet, and a volume of less than about 1 ml, wherein the chip is constructed and arranged to be fluid communicable with an apparatus constructed and arranged to address a well of a microplate. - View Dependent Claims (24, 25, 26, 27, 28)
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29. An apparatus, comprising:
a chip comprising a predetermined reaction site having an inlet, an outlet, and a volume of less than about 1 ml, wherein each predetermined reaction site overlaps at least one well of a microplate. - View Dependent Claims (30, 31, 32, 33, 34)
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35. An apparatus, comprising:
a substantially liquid-tight chip comprising a predetermined reaction site having a volume of less than about 1 ml, wherein the predetermined reaction site is constructed and arranged to maintain at least one living cell at the predetermined reaction site. - View Dependent Claims (36, 37)
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38. An apparatus, comprising:
a chip produced by a process including the step of fastening two components to produce a portion of the chip defining a predetermined reaction site having a volume of less than about 1 ml, wherein the predetermined reaction site is constructed and arranged to maintain at least one living cell at the predetermined reaction site. - View Dependent Claims (39, 40)
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41. An apparatus, comprising:
a chip comprising a predetermined reaction site having a volume of less than about 1 ml, the predetermined reaction site constructed and arranged to maintain at least one living cell at the predetermined reaction site, wherein the predetermined reaction site has a nonzero evaporation rate of less than about 100 microliters/day. - View Dependent Claims (42, 43, 44)
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45. In a method of producing a chip comprising a predetermined reaction site having a volume of less than 1 ml, the improvement comprising:
attaching a first component of the chip to a second component of the chip with or without auxiliary adhesive to produce a portion of the chip that defines the predetermined reaction site. - View Dependent Claims (46, 47, 48, 49, 50, 51, 52, 53, 54)
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55. An apparatus, comprising:
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a predetermined reaction site having a volume of less than about 1 ml; and
a membrane substantially transparent to incident electromagnetic radiation in the infrared to ultraviolet range having a pore size less than 2.0 microns in fluid communication with the predetermined reaction site. - View Dependent Claims (56)
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57. An apparatus, comprising:
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a predetermined reaction site having a volume of less than about 1 ml, constructed and arranged to carry out a chemical or biological reaction promoted by or monitored by electromagnetic radiation within a predetermined wavelength range; and
a membrane, transparent to electromagnetic radiation within the predetermined wavelength range to the extent necessary to promote or monitor the reaction, having a pore size of less than 2.0 microns in fluid communication with the predetermined reaction site. - View Dependent Claims (58, 59, 60, 61, 62, 63, 64, 65)
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66. An apparatus, comprising:
a chip comprising a first predetermined reaction site having a volume of less than about 1 ml and a second predetermined reaction site, the chip defining a pathway fluidly connecting the first predetermined reaction site and the second predetermined reaction site, wherein the pathway crosses a membrane. - View Dependent Claims (67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78)
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79. An apparatus, comprising:
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a reaction site having a first portion and a second portion separated by a membrane; and
at least a first and a second channel in fluidic communication with the second portion of the reaction site. - View Dependent Claims (80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105)
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106. A method, comprising:
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providing a substrate having a surface into which is fabricated a plurality of reaction sites, at least one reaction site having a volume less than about 2 ml and divided by a substantially cell impermeable membrane into at least a cell culture portion containing cells and a reservoir portion not containing cells, the reservoir portion being fluidly connected to at least a first and a second channel fabricated into the surface of the substrate;
introducing at least one test compound into at least one of the plurality of reaction sites; and
monitoring the effect of the at least one test compound on cells located within the cell culture portion. - View Dependent Claims (107, 108, 109, 110, 111, 112, 113, 114, 115, 116)
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Specification