Microfluidic sample chip, assay system using such a chip, and PCR method for detecting DNA sequences
Inventors
Assignees
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Publication Number
US-11607684-B2
Publication Date
2023-03-21
Expiration Date
Abstract
A microfluidic sample chip to test biological samples, especially for a PCR-type and/or fluorescence assay. The chip being in the shape of a hollow block having at least one chamber delimited by an upper wall, a lower wall and at least one side wall, into which a sample can be introduced for testing. The lower wall of the block is made of a material with a high thermal conductivity and the upper wall is made of a material with a low thermal conductivity. Preferably, the upper wall is preferably permeable to radiation in the visible spectrum between 400 and 700 nm. The block having at least two openings through which the sample can be introduced into at least one of the chambers and through which the air present in the chamber can be evacuated when the sample is introduced.
Core Innovation
The invention relates to a system to analyze PCR-type samples contained in at least one chamber of a micro-fluidic sample chip for PCR or fluorescence analysis. The system is implemented as a hollow block comprising the at least one chamber delimited by an upper wall, a lower wall and at least one side wall, with sample introduction into the chamber. The hollow block includes at least a lower side and an upper side parallel to each other, where the lower side is disposed onto the lower wall and the upper side is disposed on the upper wall.
The upper wall is made of a material having a thermal conductivity lower than a material of the lower side, and the upper side is permeable, at least in the at least one chamber, to radiations having a wavelength between 300 nm and 900 nm. The hollow block comprises at least two openings to introduce the sample into the at least one chamber and to discharge pressure in the chamber during the introduction of the sample. An optical measurement instrument comprising a camera optically observes the samples with a spatial resolution through a transparent portion traversed by light rays located above the chamber.
A thermalization film provides thermal cycling to increase or decrease a temperature of the micro-fluidic sample chip and the samples therein, in thermal contact with the lower side of the micro-fluidic sample chip. Sealers close the at least two openings to maintain a relative internal pressure of at least 5000 Pa (50 mbar), with temperature increase causing chamber expansion to improve thermal contact between the lower side and the thermalization film. A pressure controller maintains a relative external pressure greater than 50 mbar over the entire upper side, to provide substantially uniform thermal contact between the lower side and the thermalization film.
The pressure controller is configured in specific constructions, including a plate of transparent material associated with a frame arranged at a periphery of the plate and springs configured to apply pressure onto the frame, and alternatively a housing having outer dimensions of the micro-fluidic sample chip. The document further specifies that the sealers are configured to maintain a relative internal pressure of at least 50000 Pa (500 mbar). The system is configured for PCR or fluorescence analysis, including digital PCR and digital droplet PCR.
Claims Coverage
The independent claims (clm-00001, clm-00009, clm-00017) each define a micro-fluidic PCR/fluorescence analysis system with a hollow-block chip, thermal contact management via a thermalization film, and pressure-controlled thermal coupling plus camera-based spatial optical measurement. Across the independent claims, the core claim structure includes coordinated internal pressure, external pressure, a radiation-permeable upper wall with a transparent optical portion, and optical observation with spatial resolution.
Hollow-block micro-fluidic PCR/fluorescence analysis chip with radiation-permeable upper wall
A hollow block comprising at least one chamber delimited by an upper wall, a lower wall and at least one side wall, with a sample to be introduced, where the upper side is made of a material having a thermal conductivity lower than a material of the lower side and the upper side is permeable to radiations having a wavelength between 300 nm and 900 nm, and where the upper wall comprises a transparent portion traversed by light rays located above the chamber.
Thermalization film in thermal contact with the lower side for thermal cycling
A thermalization film to increase or decrease, by a thermal cycling, a temperature of the micro-fluidic sample chip and the samples therein, in thermal contact with the lower side of the micro-fluidic sample chip.
Sealers to maintain relative internal pressure to improve thermal contact
Sealers to close the at least two openings in the at least one chamber to maintain a relative internal pressure of at least 5000 Pa (50 mbar), where an increase in temperature of the samples causes the at least one chamber to expand, thereby improving thermal contact between the lower side and the thermalization film.
Pressure controller maintaining relative external pressure for substantially uniform thermal contact
A pressure controller to maintain a relative external pressure greater than 50 mbar over the entire upper side of the micro-fluidic sample chip to provide substantially uniform thermal contact between the lower side and the thermalization film.
Camera-based optical measurement with spatial resolution through transparent upper portion
An optical measurement instrument comprising a camera to optically observe the samples with a spatial resolution.
Pressure controller construction using transparent plate, frame, and springs
The pressure controller is formed by a plate of transparent material associated with a frame arranged at a periphery of the plate and springs configured to apply a pressure onto the frame.
Housing-based pressure controller applying pressure to upper and lower chip walls
The pressure controller is formed by a housing having outer dimensions of the micro-fluidic sample chip to house the micro-fluidic sample chip therein, where walls of the housing exert a pressure onto the upper and lower walls of the micro-fluidic sample chip as the temperature of a sample increases.
PCR in digital PCR or digital droplet PCR formats
The system is configured to perform PCR including digital PCR (dPCR) or digital droplet PCR (ddPCR).
Higher internal pressure defined for sealers
The sealers are configured to maintain the relative internal pressure of at least 50000 Pa (500 mbar) in the at least one chamber.
Across clm-00001, clm-00009, and clm-00017, the independent claims share a hollow-block micro-fluidic PCR/fluorescence chip with a radiation-permeable upper wall and transparent optical portion, a thermalization film providing thermal cycling in contact with the lower side, sealers maintaining relative internal pressure to improve thermal contact, and a pressure controller maintaining relative external pressure to provide substantially uniform thermal contact. Each independent claim additionally requires camera-based optical measurement with spatial resolution, and further includes specific pressure-controller constructions and, in dependent refinements, digital PCR/digital droplet PCR and higher internal-pressure limits.
Stated Advantages
Improving thermal contact between the lower side of the micro-fluidic sample chip and the thermalization film via chamber expansion caused by temperature increase.
Providing substantially uniform thermal contact between the lower side of the micro-fluidic sample chip and the thermalization film.
Enabling optical observation of samples with spatial resolution through the transparent portion of the upper wall.
Documented Applications
Analyzing PCR-type biological samples contained in at least one chamber of a micro-fluidic sample chip for PCR or fluorescence analysis.
Performing polymerase chain reaction including digital PCR and digital droplet PCR formats.
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