Tuesday, January 26, 2010

Nanotextured Microwell and Micromesa Biomolecular Arrays for Improved Chemical Analysis Revealed in IBM Patent


Biomolecular arrays have quickly developed into an important tool in life science research. Microarrays, or densely-packed, ordered arrangements of miniature reaction sites on a suitable substrate, enable the rapid evaluation of complex biomolecular interactions. Because of their high-throughput characteristics and low-volume reagent and sample requirements, microarrays are now commonly used in gene expression studies, and they are finding their way into significant emerging areas such as proteomics and diagnostics.

International Business Machines (IBM)  (Armonk, NY) earned U.S. Patent 7,651,872 for improved biomolecular arrays with nano-textured structures for biochemical and chemical analysis.  The analytical device consists of a substrate across which is distributed an array of discrete regions of a porous substance that is formed from a porogen-containing organosilicate material.  The arrays have high areal density.  The nanostructured arrays permit the collection of data with good signal/noise ratio. The array sites have a consistent and uniform spot morphology.

According to IBM inventors Mark Whitney Hart, Ho-Cheol Kim, Robert Dennis Miller and Gregory Michael Wallraff, the porous substance is designed to bind chemical targets useful in biotechnology applications, such as gene expression, protein, antibody, and antigen experiments.

The  chemically active regions are preferably optically isolated from each other and may be shaped to enhance detection of optical radiation emanating from the porous substance, e.g., as a result of irradiation of the regions with ultraviolet light. The discrete regions may be configured as microscopic wells within the substrate, or they may reside on top of the substrate in the form of microscopic mesas.

The arrays are used in chemical and biochemical applications, and include a substrate with an array of discrete regions of a porous substance designed to bind chemical targets. These regions are preferably optically isolated from each other and may be shaped to enhance detection of optical radiation emanating from the porous substance, e.g., fluorescence as a result of irradiation of the regions with ultraviolet, visible, or infrared light. For example, these regions may have a parabolic or hemispherical contour.  

FIG. 1 shows a plan view of a biochip 10 that includes a substrate into which a number of small wells  or microwells have been formed. The microwells have nanoporous material within them , resulting in a significant increase in effective surface area, and thereby permitting more sensitive detection measurements to be made. The microwells and the micromesas may have a characteristic transverse (lateral) dimension of about 1-500 microns, but most preferably between 1-10 microns (e.g., if the microwells have a circular cross section, their diameters may be about 1 micron; for a square cross section, the corresponding square may be about 1 micron times 1 micron).

 The depth of each microwell (or height of the micromesas discussed below) may be about 1-50 microns or more preferably 0.5-50 microns. The width of the substrate that separates adjacent microwells  (or the distance separating the micromesas) is preferably sufficient to optically isolate one microwell from adjacent microwells, e.g., 0.1-10 microns. The material separating adjacent microwells  is preferably optically opaque; if this material is not intrinsically optically opaque, the microwells may have roughened surfaces so that light is scattered, or these surfaces may be coated.

FIG. 3 is an enlarged view of a microwell that includes optical and hydrophobic coatings.

FIG. 4 is a cross sectional side view of a biochip in which an optical coating has been applied to the underside of the substrate.  



FIG. 5 shows porous material within the microwells of the biochip. One preferred nanoporous material is formed using an organosilicate material (such as methylsilsesquioxane, or MSSQ) that has been mixed with a sacrificial porogen in a solvent.

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