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Assembly of arrays on chips segmented from wafers

a technology of arrays and wafers, applied in the field of material science and analytical chemistry, can solve the problems of high parallel array format of analysis, sample processing and analysis by way, and has not been described to date, and none of the array formation techniques of the prior art permit the formation of arrays in real tim

Inactive Publication Date: 2005-11-03
HUANG HIU +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0025] The present invention provides methods, compositions and processes relating to the implementation of bioanalytical assay procedures for multiplexed molecular interaction analysis. The processes of the invention employ a multiplicit

Problems solved by technology

However, the integration of sample processing and a highly parallel array format of analysis by way of microfluidic operations, highly desirable in connection with the miniaturization of biochemical and analytical assay procedures, has not been described to date.
Therefore, none of the techniques of array formation of the prior art permit the real-time formation of arrays subsequent to completion of the binding interaction of interest.
One drawback of the process is the difficulty in controlling the mono-dispersity of the resulting magnetic Latex, and the process does not appear well suited for the generation of fluorescent magnetic particles
U.S. Pat. No. 5,356,713 to Charmot et al discloses magnetizable composite microspheres which are useful in biological applications but are limited by their size distribution to other applications.
A two-step reactive process such as this suffers from the drawback of possible inhibition of polymerization by the fluorescent dye or conversely bleaching of the fluorescence by the shell polymerization process.
(Caruso et al “Magnetic Core-Shell Particles: Preparation of Magnetite Multilayers on Polymer Latex Microspheres” Adv. Mater. 1999, 11, 950-953) A shell applied by electrostratic physisorption is not desirable for bioanalytical assays because it is chemically unstable under changes of assay conditions, particularly salt concentration, and promotes non-specific adsorption and denaturation of charged biomolecules; the particles described in this prior art reference are unsuitable in connection with the assay formats contemplated herein.

Method used

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  • Assembly of arrays on chips segmented from wafers
  • Assembly of arrays on chips segmented from wafers
  • Assembly of arrays on chips segmented from wafers

Examples

Experimental program
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example 1

Optically Programmable Array Formation

[0124] As illustrated in FIG. 9, LEAPS serves to simultaneously assemble multiple random encoded subarrays and to “drag-and-drop” these subarrays into separate, but proximate locations on the chip within a common, enclosed liquid environment. Two sets of beads (2.8 μm Oligo-(dT)25, Dynal, Oslo, Norway), dispensed from separate reservoirs A and B, were simultaneously assembled into distinct subarrays within the same fluid; subarrays were then simultaneously placed into desired destinations as directed by spatially varying illumination profiles which were generated and projected onto the substrate by a PC-programmable illumination pattern generator (described in U.S. Ser. No. 09 / 397,793, filed Sep. 17, 1999, which is incorporated herein by reference in its entirety). This drag-and-drop operation reduced the separation between the two sub-arrays from approximately 250 μm to 20 μm. Beads were moved at 5 V at a frequency of 2 kHz; total power projec...

example 2

Array Formation on Patterned Surface

[0125] Illustrated in FIG. 10 is an array of encoded beads assembled on a patterned silicon chip using an AC voltage of 1-2 V and a frequency of 100-150 Hz, applied across a 100 μm electrode gap filled with an aqueous bead suspension; a thermal oxide (˜1000 Å) on the substrate was patterned by etching the oxide to a thickness of 50-100 Å in a set of square features (˜30×30 μm2) on 130 μm centers; arrays of similar layout also can be produced in response to suitable illumination patterns. Each sub-array shown here contains approximately 80 beads coupled with anti-cytokine monoclonal antibodies. Carboxylate-modified polystyrene beads of 5.5 μm diameter (Bangs Laboratory, Fishers, Ind.) were stained with a combination of two types of fluorescent dyes and were then functionalized with anti-cytokine-mAb. The assembly process ensures collection of all beads at the substrate surface. Bead encoding was as follows: IL-2 (Bright Red); IL-4 (Dim Red); IL-6 ...

example 3

Formation of Arrays of Magnetic Nanoparticles

[0126] Colloidal particles exhibiting a finite diamagnetic susceptibility, when disposed on a planar substrate can be assembled into ordered arrays in response to increasing magnetic fields. Commercially available superparamagnetic particles (Dynal, Oslo, NO), dispersed from a fluid suspension onto the planar surface of the lower of two parallel bounding surfaces of a fluid cell (“sandwich” geometry), when exposed to a homogeneous axial magnetic field (oriented normal to the substrate plane), will form ordered assemblies. As a function of increasing magnetic field strength, and for given diamagnetic susceptibility of the particles as controlled by the manufacturing process known to the art, ordered planar assemblies and linear strings of beads oriented normal to the substrate can be formed. Permanent magnets can be designed so as to produce the field strength required to realize the desired configuration of the assembly. Requisite magnet...

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Abstract

The present invention provides a method for the generation of novel libraries of encoded magnetic particles from sub-libraries of by the generation of novel sub-libraries of magnetic nanoparticles and encoded particles. The sub-libraries are functionalized on demand are useful in the formation of arrays. The present invention is especially useful for performing multiplexed (parallel) assays for qualitative and / or quantitative analysis of binding interactions of a number of analyte molecules in a sample.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of International Application Serial No. PCT / US01 / 20179, filed Jun. 21, 2001 which claims priority for U.S. Provisional Application Ser. No. 60 / 213,106 filed Jun. 21, 2000. All the above-referenced applications are expressly incorporated herein by referenceFIELD OF THE INVENTION [0002] The present invention generally relates to the field of materials science and analytical chemistry. [0003] The present invention discloses a process for the production of libraries of encoded magnetic particles, and the formation of planar assemblies inclusive of such particles. The present invention also discloses a platform for the implementation of multistep bioanalytical assay protocols permitting the integration of sample preparation steps with the simultaneous analysis of binding interactions between multiple types of analytes and binding agents. BACKGROUND OF THE INVENTION [0004] Many bioanalytical procedur...

Claims

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Application Information

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IPC IPC(8): B01J19/00C12M1/34G01N21/64C12Q1/68C12Q1/6837G01N33/53G01N33/543G01N33/553G01N33/58G01N35/00
CPCB01J19/0046Y10T436/11B01J2219/00315B01J2219/00497B01J2219/005B01J2219/00527B01J2219/00545B01J2219/00576B01J2219/00585B01J2219/00596B01J2219/00644B01J2219/00648B01J2219/00653B01J2219/00722B01J2219/00725C12Q1/6837G01N27/745G01N33/5434G01N33/54346G01N33/587G01N2035/00564G01N2035/00762G01N2446/20G01N2446/64B01J2219/00286C12Q1/6876C12Q1/6813C12Q2565/513C12Q2563/143C12Q2563/107C12Q2563/155
Inventor HUANG, HIUCHAU, CHIU
Owner HUANG HIU
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