Integrated analysis devices and related fabrication methods and analysis techniques
AssigneeBionanomatrix, Inc.
InventorsHan Cao, Michael D. Austin, Parikshit A. Deshpande, Mark Kunkel, Alexey Y. Sharonov, Michael Kochersperger
Life of this patent
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Abstract
Provided are integrated analysis devices having features of macroscale and nanoscale dimensions, and devices that have reduced background signals and that reduce quenching of fluorophores disposed within the devices. Related methods of manufacturing these devices and of using these devices are also provided.
Claims100
An analysis device, comprising:
- a first substrate;
- a second substrate;
- a first inlet port extending through at least a portion of the first substrate, the second substrate, or both, so as to place a first interconnector channel in fluid communication with the environment exterior to the analysis device;
- and
- a first front-end branched channel region, comprising at least a primary channel characterized as having a cross-sectional dimension in the range of from less than about 10,000 nm and at least two secondary channels, placing the first interconnector channel into fluid communication with a nanochannel analysis region,
- the nanochannel analysis region comprising at least one nanochannel characterized as having a cross-sectional dimension less than that of the primary channel, and wherein the ratio of the cross-sectional dimensions of the primary channel to the nanochannel is in the range of from about 100 to about 10,000.
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A method of fabricating an analysis device, comprising:
- bonding a first substrate and a second substrate,
- at least one of the substrates comprising at least one channel having a width in the range of from about 10 nm to about 10,000 nm,
- the bonding giving rise to an enclosed conduit disposed between the substrates, the enclosed conduit being capable of transporting a fluid therethrough.
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A method of analysis, comprising:
- translocating a macromolecule through at least two channels of successively decreasing width such that at least a portion of the macromolecule is elongated while disposed in the narrowest of the channels;
- the ratio of the widths of the widest and narrowest channels is in the range of from about 1 to about 107;
- detecting a signal from the molecule while it resides in a first region of a channel having a width of from 10 nm to about 1000 nm;
- and
- correlating the signal to a property of the macromolecule.
An analysis device, comprising:
- a first substrate and a second substrate,
- the first and second substrates defining a channel disposed between the substrates,
- at least one of the first or second substrates permitting at least partial passage of electromagnetic radiation characterized as having at least one wavelength in the range of from about 10 nm to about 2500 nm;
- a first thin film surmounting at least a portion of the first substrate, the second substrate, or both,
- at least a portion of the first thin film defining at least a portion of a channel disposed between the first and second substrates, and
- the first thin film giving rise to a reduced background signal of the device when the device is illuminated by electromagnetic radiation having a wavelength in the range of from about 10 nm to about 2500 nm, relative to an identical device without said first thin film.
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An analysis device, comprising:
- a substrate configured so as to define a channel enclosed within the substrate,
- the substrate being transparent to electromagnetic radiation having at least one frequency component in the range of from about 10 nm to about 2500 nm.
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A method of fabricating an analysis device, comprising:
- disposing a first substrate, a second substrate, and a first thin film layer so as to define a channel disposed between the first and second substrates,
- the first thin film layer being selected such that said layer reduces the background signal of the device when the device is illuminated by electromagnetic radiation having a wavelength in the range of from about 10 nm to about 2500 nm, relative to an identical device without said first thin film;
- and
- bonding the first thin film layer to the first substrate, the second substrate, or both.
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A method of fabricating an analysis device, comprising:
- disposing a sacrificial template within a workpiece comprising a material that is transparent to electromagnetic radiation having a wavelength in the range of from about 10 nm to about 5000 nm;
- removing at least a portion of the sacrificial template so as to give rise to a channel disposed within the workpiece,
- at least a portion of the channel having a cross-sectional dimension in the range of from about 5 nm to about 5000 nm.
A method of analyzing a fluorescently labeled molecule, comprising:
- placing at least a portion of the fluorescently labeled molecule into a channel within an analysis device,
- the analysis device having at least a first substrate, a second substrate, and a first thin film configured to give rise to the channel being disposed between the first and second substrates, the first thin film bonded to the first substrate, the second substrate, or both,
- the fluorescently labeled molecule capable of emitting electromagnetic radiation of an emission wavelength when the sample is illuminated by electromagnetic radiation of an excitation wavelength in the range of from about 10 nm to about 2500 nm,
- the first thin film reducing the background signal of the device when the device is illuminated by electromagnetic radiation of the excitation wavelength, relative to an identical device without said first thin film, and
- collecting electromagnetic radiation of the emission wavelength emitted from the fluorescently labeled molecule.
Dependencies are inferred from the claim text.