Abstract:
A method and system for heating and/or inspecting a portable microfluidic assay cartridge for performing an assay includes receiving the assay cartridge on a receiving region of a translatable table under automated control, heating the cartridge, during performance of the assay, with a planar radiant heater plate, the heater plate having an aperture through which an inspection axis extends, and/or inspecting the cartridge using an optical system constructed to inspect the cartridge along the inspection axis by reading a fluorescent light signal which passes through the aperture in the heater plate. In addition, the cartridge moves with movement of the translation table, and the heater plate and optical system may be stationary, and the inspection axis may be fixed.
Abstract:
A method of making at least a portion of at least one microfluidic actuator having a flexible diaphragm portion and an opposite surface portion, the diaphragm and opposite surface each having opposed faces, at least one of the faces comprising surface-activated PDMS, and the opposed faces being arranged such that when the opposed faces contact each other, they form a fluidic seal, including performing repeated make-and-break-contact protocol on the contacting opposed faces until the tendency for permanent bonds to form between the contacting faces has been neutralized, thereby enabling the diaphragm portion to perform actuated movements to engage and disengage with the opposite surface portion, without the diaphragm sticking to the opposite surface portion.
Abstract:
A method of flowing a fluid with a tracer in a microfluidic channel of an assay device and detecting the tracer for determining the channel location or condition of the channel.
Abstract:
A method of forming a pneumatically controlled microfluidic device containing a micro-fluidic network that includes micro-elements in the form of micro-particles or micro-length hollow flow elements, and a pneumatic network that includes pneumatic micro-channels and micro-valve features enabling membrane valves to operate to control fluid conditions in the microfluidic network, including the steps (a) forming two portions, denominated fluidic layer, in which microfluidic channels are formed, and pneumatic layer, in which pneumatic micro-channels and micro-valve features are formed, each having a backing that is rigid in the plane of extent of the layers, (b) providing an intervening elastic membrane, and (c) permanently bonding both layers to opposite sides of the membrane, the permanent bonding of the membrane to the fluidic layer being effective to permanently enclose a set of inserted micro-elements in the fluidic network and relate the two layers to enable pneumatic control of fluid conditions in the microfluidic network.
Abstract:
A method of making at least a portion of at least one microfluidic actuator having a flexible diaphragm portion and an opposite surface portion, the diaphragm and opposite surface each having opposed faces, at least one of the faces comprising surface-activated PDMS, and the opposed faces being arranged such that when the opposed faces contact each other, they form a fluidic seal, including performing repeated make-and-break-contact protocol on the contacting opposed faces until the tendency for permanent bonds to form between the contacting faces has been neutralized, thereby enabling the diaphragm portion to perform actuated movements to engage and disengage with the opposite surface portion, without the diaphragm sticking to the opposite surface portion.
Abstract:
Microfluidic devices are provided for conducting fluid assays, for example biological assays, that have the ability to move fluids through multiple channels and pathways in a compact, efficient, and low cost manner. Discrete flow detection elements, preferably extremely short hollow flow elements, with length preferably less than 700 micron, preferably less than 500 micron, and internal diameter preferably of between about 50+/−25 micron, are provided with capture agent, and are inserted into microfluidic channels by tweezer or vacuum pick-and-place motions at fixed positions in which they are efficiently exposed to fluids for conducting assays. Close-field electrostatic attraction is employed to define the position of the elements and enable ready withdrawal of the placing instruments. The microfluidic devices feature flow elements, channels, valves, and on-board pumps that are low cost to fabricate accurately, are minimally invasive to the fluid path and when implemented for the purpose, can produce multiplex assays on a single portable assay cartridge (chip) that have low coefficients of variation. Novel methods of construction, assembly and use of these features are presented, including co-valent bonding of selected regions of faces of surface-activatable bondable materials, such as PDMS to PDMS and PDMS to glass, while contiguous portions of one flexible sheet completes and seals flow channels, fixes the position of inserted analyte-detection elements in the channels, especially short hollow flow elements through which sample and reagent flow, and other portions form flexible valve membranes and diaphragms of pumps. A repeated make-and-break-contact manufacturing protocol prevents such bonding to interfere with moving the integral valve diaphragm portions from their valve seats defined by the opposed sheet member, which the flexible sheet material engages. Preparation of two subassemblies, each having a backing of relatively rigid material, followed by their assembly face-to-face in a permanent bond is shown. Hollow detection flow elements are shown fixed in channels, that provide by-pass flow paths of at least 50% of the flow capacity through the elements; in preferred implementations, as much as 100% or more. Metallized polyester film is shown to have numerous configurations and advantages in non-permanently bonded constructions. A method of preparing detection elements for an assay comprises batch coating detection elements, or hollow flow elements by mixing and picking and placing the elements in flow channels of a microfluidic device, capturing the flow elements by bonding two opposed layers while sealing the flow channels.
Abstract:
A microfluidic assay device that defines a micro-fluidic flow channel (44) having a flow axis, in which a series of discrete, axially-spaced apart, transparent hollow flow elements (32) are secured in fixed position, each flow element having at least one axially-extending flow passage through its interior, assay capture agent fixed to the interior surface of the elements for capture of an analyte in liquid flowing through the interior of the flow elements, the device constructed to enable light to be transmitted out of the elements for reading of fluorescence from captured analyte, wherein: the exterior axially-extending surfaces of the flow elements are free of active capture agent, while at least part of the interior surfaces carry deposits of active capture agent exposed to flow through the elements.
Abstract:
An operating and reading instrument for performing an assay employing a portable microfluidic assay cartridge, the instrument comprising a translatable table under automated control, the translatable table carrying a receiving region for the portable cartridge and carrying a port system connectible to the cartridge that includes at least one remotely automated valve carried by the translatable table, the valve arranged to apply pressurized flowable substance at selected times to the cartridge while the cartridge is on the translatable table.
Abstract:
A method of making at least a portion of at least one microfluidic actuator having a flexible diaphragm portion and an opposite surface portion, the diaphragm and opposite surface each having opposed faces, at least one of the faces comprising surface-activated PDMS, and the opposed faces being arranged such that when the opposed faces contact each other, they form a fluidic seal, including performing repeated make-and-break-contact protocol on the contacting opposed faces until the tendency for permanent bonds to form between the contacting faces has been neutralized, thereby enabling the diaphragm portion to perform actuated movements to engage and disengage with the opposite surface portion, without the diaphragm sticking to the opposite surface portion.
Abstract:
A method for performing a combined protein and nucleic acid assay on a target captured by a capture agent, includes providing a microfluidic device having a microfluidic channel network having at least one microfluidic channel, the channel arranged to receive fluid, the device having at least two micro-particles disposed in fixed position in the channel, the micro-particles being functionalized with a capture agent for the assay, one of the micro-particles in the channel being functionalized with an antibody or antigen capture agent and another of the micro-particles being functionalized with a nucleic acid capture agent. In some embodiments, the network may have at least two microfluidic channels, each channel of the two channels arranged to receive portions of the same fluid and to be fluidicly isolatable from each other, the device having at least two micro-particles disposed in fixed position in the network channels, the micro-particles being functionalized with a capture agent, one of the micro-particles in one of the channels being functionalized with an antibody or antigen capture agent and another of the micro-particles in another of the channels being functionalized with a nucleic acid capture agent. The method may also include detecting both protein and nucleic acid present in an input sample using the respectively functionalized micro particles. In some embodiments, the micro particles may be micro-length tubes or glass nano reactors.