Nanonozzle device arrays: their preparation and use for macromolecular analysis

#The present invention pertains to the field of nanoscale devices. The present invention also pertains to the field of macromolecular sequencing, particularly the field of DNA sequencing and characterization.

#Various scientific and patent publications are referred to herein. Each is incorporated by reference in its entirety.

#Biomolecules such as DNA or RNA are long molecules composed of nucleotides, the sequence of which is directly related to the genomic and post-genomic gene expression information of an organism. In most cases, the mutation or rearrangement of the nucleotide sequences during an individual's life span can lead to disease states such as genetic abnormalities or cell malignancy. In other cases, the small amount of sequence differences among each individual reflects the diversity of the genetic makeup of the population. Because of these differences in genetic sequence, certain individuals respond differently to environmental stimuli and signals, including drug treatments. For example, some patients experience positive response to certain compounds while others experience no effects or even adverse side effects.

#The summary, as well as the following detailed description, is further understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there are shown in the drawings exemplary embodiments of the invention; however, the invention is not limited to the specific methods, compositions, and devices disclosed. In addition, the drawings are not necessarily drawn to scale. In the drawings:

#FIG. 1a is a schematic view of a DNA sequencer showing linearized double-stranded DNA passing through a nanochannel into an outlet reservoir, where a measurement device detects physical, chemical, electrical, or other changes in the outlet reservoir or within the nanochannel related to the passage of the DNA;

#FIG. 1b depicts a DNA molecule flowing through a nanonozzle constriction at the end of a nanochannel, wherein the DNA molecule is a double-stranded DNA having a first strand comprising a nucleic acid sequence of SEQ ID NO: 1 and a complementary strand comprising a nucleic acid sequence of SEQ ID NO: 2;

#As used herein, the term “substantially linear” means that the conformation of at least a portion of a long molecule, such as, but not limited to, a polynucleic acid comprising 200 nucleic acids linked together, does not loop back on itself or does not containing any sharp bends or curves greater than about 360 degrees.

#As used herein, the term “nanochannel” means a conduit, channel, pipe, duct, or other similar structure having at least one nanoscale dimension.

#The present invention may be understood more readily by reference to the following detailed description taken in connection with the accompanying figures and examples, which form a part of this disclosure. It is to be understood that this invention is not limited to the specific devices, methods, applications, conditions or parameters described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed invention. Also, as used in the specification including the appended claims, the singular forms “a,” “an,” and “the” include the plural, and reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise. The term “plurality”, as used herein, means more than one. When a range of values is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. All ranges are inclusive and combinable.