Abstract: In one aspect, methods of biomolecular analysis are described herein. Briefly, a method comprises providing a composition comprising glycosaminoglycans and contacting the composition with a membrane comprising at least one nanopore. An electric field is applied across the nanopore, and data of glycosaminoglycan translocation events through the nanopore are recorded. A molecular weight distribution of the glycosaminoglycans is derived from the data.

Abstract: Described are methods of detecting modified nucleotide bases in a DNA sample using specific DNA glycosylases to excise target modified bases. DNA molecules are then labeled using a DNA polymerase lacking 3??5? exo-nuclease activity and strand displacement activity. The methods can be used to detect epigenetic changes and DNA damage. Provided are methods for diagnosing a disease or condition, determining risk of a disease or condition, identifying appropriate treatment, monitoring effectiveness of treatment, and monitoring side effects of treatment in subjects based on detection of modified bases. Also provided are methods for determining environmental exposure, or an environmental exposure time, of a biological sample containing DNA. Also provided are kits, systems, and devices for performing the described methods.

Abstract: In one aspect, methods are described herein for the selective detection and quantitative analysis of biological molecule compositions. A method described herein comprises providing a mixture comprising biological molecules, such as DNA, RNA or proteins, complexed with a translocating agent, such as another DNA or protein, and non-complexed biological molecules. The mixture is contacted with a membrane comprising at least one nanopore and an electric field is applied across the nanopore to selectively translocate the biological molecules complexed with the translocating agent through the at least one nanopore. Concentration of the complexed biological molecules is determined based on the translocation rate of said molecules.

Abstract: The present disclosure describes a method of encapsulating cells in a crosslinked alginate microbead using a microfluidic encapsulation device.

Abstract: In one aspect, methods of biomolecular analysis are described herein. Briefly, a method comprises providing a composition comprising glycosaminoglycans and contacting the composition with a membrane comprising at least one nanopore. An electric field is applied across the nanopore, and data of glycosaminoglycan translocation events through the nanopore are recorded. A molecular weight distribution of the glycosaminoglycans is derived from the data.

Abstract: Described are methods of detecting modified nucleotide bases in a DNA sample using specific DNA glycosylases to excise target modified bases. DNA molecules are then labeled using a DNA polymerase lacking 3??5? exo-nuclease activity and strand displacement activity. The methods can be used to detect epigenetic changes and DNA damage. Provided are methods for diagnosing a disease or condition, determining risk of a disease or condition, identifying appropriate treatment, monitoring effectiveness of treatment, and monitoring side effects of treatment in subjects based on detection of modified bases. Also provided are methods for determining environmental exposure, or an environmental exposure time, of a biological sample containing DNA. Also provided are kits, systems, and devices for performing the described methods.

Abstract: Methods for fabricating materials useful for optical detection in microfluidic and nanofluidic devices, such as those used in nanopore-based nucleic acid sequencing are described herein. In certain variations, a method of reducing background fluorescence in a MEMS material may include the step of treating a surface of the MEMS material with a low energy ion beam.

Abstract: In one aspect, methods are described herein for the selective detection and quantitative analysis of biological molecule compositions. A method described herein comprises providing a mixture comprising biological molecules, such as DNA, RNA or proteins, complexed with a translocating agent, such as another DNA or protein, and non-complexed biological molecules. The mixture is contacted with a membrane comprising at least one nanopore and an electric field is applied across the nanopore to selectively translocate the biological molecules complexed with the translocating agent through the at least one nanopore. Concentration of the complexed biological molecules is determined based on the translocation rate of said molecules.

Abstract: Methods for fabricating materials useful for optical detection in microfluidic and nanofluidic devices, such as those used in nanopore-based nucleic acid sequencing are described herein. In certain variations, a method of reducing background fluorescence in a MEMS material may include the step of treating a surface of the MEMS material with a low energy ion beam.

Abstract: In one aspect, methods of nanopore formation in solid state membranes are described herein, In some embodiments, a method of forming an aperture comprises providing at least one solid state membrane in a chamber, selecting a first dose of ions sufficient to provide a first aperture of predetermined diameter through the membrane and exposing a surface of the membrane at a first location to the first dose of ions in a focused ion beam having a focal point of diameter less than or equal to about 1 nm to remove material from the membrane at the first location thereby providing the first aperture having the predetermined diameter or substantially the predetermined diameter.

Abstract: In one aspect, methods of nanopore formation in solid state membranes are described herein, In some embodiments, a method of forming an aperture comprises providing at least one solid state membrane in a chamber, selecting a first dose of ions sufficient to provide a first aperture of predetermined diameter through the membrane and exposing a surface of the membrane at a first location to the first dose of ions in a focused ion beam having a focal point of diameter less than or equal to about 1 nm to remove material from the membrane at the first location thereby providing the first aperture having the predetermined diameter or substantially the predetermined diameter.

Abstract: A dual pipe drill string system having increased fluid flow. The dual pipe system comprises a plurality of pipe sections, each pipe section having an inner rod and an outer pipe. The inner rod and the outer pipe of each pipe section may be coupled to the inner rod and outer pipe of an adjacent pipe section. An annulus between the inner rod and the outer pipe defines a fluid flow path through the dual pipe system. The outer pipe defines a shoulder at each end of an individual pipe section. The inner rod defines at least one stop for maintaining the inner rod within the outer pipe. A spacing assembly disposed around the circumference of the inner rod defines paths for fluid flow and maintains a minimum distance between the stop and the shoulder at one end of outer pipe of the pipe section.

Abstract: A dual pipe drill string system having increased fluid flow. The dual pipe system comprises a plurality of pipe sections, each pipe section having an inner rod and an outer pipe. The inner rod and the outer pipe of each pipe section may be coupled to the inner rod and outer pipe of an adjacent pipe section. An annulus between the inner rod and the outer pipe defines a fluid flow path through the dual pipe system. The outer pipe defines a shoulder at each end of an individual pipe section. The inner rod defines at least one stop for maintaining the inner rod within the outer pipe. A spacing assembly disposed around the circumference of the inner rod defines paths for fluid flow and maintains a minimum distance between the stop and the shoulder at one end of outer pipe of the pipe section.

Abstract: A dual pipe drill string system having increased fluid flow. The dual pipe system comprises a plurality of pipe sections, each pipe section having an inner rod and an outer pipe. The inner rod and the outer pipe of each pipe section may be coupled to the inner rod and outer pipe of an adjacent pipe section. An annulus between the inner rod and the outer pipe defines a fluid flow path through the dual pipe system. The outer pipe defines a shoulder at each end of an individual pipe section. The inner rod defines at least one stop for maintaining the inner rod within the outer pipe. A spacing assembly disposed around the circumference of the inner rod defines paths for fluid flow and maintains a minimum distance between the stop and the shoulder at one end of outer pipe of the pipe section.

Abstract: A pipe handling assembly for transporting pipe sections to and from the drill string of a horizontal boring machine. The system comprises a magazine, a cradle for supporting the magazine, a support member, a drive system, and a transfer assembly. The drive system may move the cradle and the magazine laterally on the support member or may pivot the magazine. The transfer assembly transfers pipe sections between the magazine and the spindle connection area. The magazine and the support frame are disposed above the spindle connection area such that only empty columns of the magazine are outside of the footprint of the boring machine. The magazine may be removed from the cradle when empty or full to continue with the boring operation.

Abstract: A dual pipe drill string system having increased fluid flow. The dual pipe system comprises a plurality of pipe sections, each pipe section having an inner rod and an outer pipe. The inner rod and the outer pipe of each pipe section may be coupled to the inner rod and outer pipe of an adjacent pipe section. An annulus between the inner rod and the outer pipe defines a fluid flow path through the dual pipe system. The outer pipe defines a shoulder at each end of an individual pipe section. The inner rod defies at least one stop for maintaining the inner rod within the outer pipe. A spacing assembly disposed around the circumference of the inner rod defines paths for fluid flow and maintains a minimum distance between the stop and the shoulder at one end of outer pipe of the pipe section.