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Flow-thru chip cartridge, chip holder, system & method thereof

a technology of flow-thru chip and chip holder, which is applied in fluid controllers, laboratory glassware, instruments, etc., can solve the problems of high component density, limited detection limit of hybridization on flat-surface genosensors, and high cost of genosensors

Inactive Publication Date: 2008-08-14
GOODMAN JACK +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The system achieves uniform fluid distribution and controlled flow rates, enhancing the efficiency and reliability of hybridization assays by preventing leakage and ensuring consistent fluid flow through microchannels.

Problems solved by technology

Microfabricated genosensor devices are compact, but with a high density of components.
As in membrane hybridization, the detection limit for hybridization on flat-surface genosensors is limited by the quantity of DNA that can be bound to a two dimensional area.
Another limitation of these approaches is the fact that a flat surface design introduces a rate-limiting step in the hybridization reaction, i.e., diffusion of target molecules over relatively long distances before encountering complementary probes on the surface.
This characteristic distinguishes the FTCs from other three-dimensional arrays, such as porous aluminum oxide, which utilizes non-uniform hole sizes (and thus variable surface areas) and prevents straightforward normalization of results.
In practice, however, a conventional technique of holding and utilizing FTCs has led to several problems.
This technique, however, leads to substantial leakage problems.
While initial capillary action draws fluid into the microchannels, blockage problems can quickly decrease the flow rate.
Further, utilizing this technique is disadvantageous in that the flow rate is not selectively controllable.
In other words, this conventional cartridge does not facilitate uniform flow during the passage of fluid through the flow-through device.
Therefore, this type of conventional design is inadequate to address fluid flow and leakage issues.

Method used

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  • Flow-thru chip cartridge, chip holder, system & method thereof
  • Flow-thru chip cartridge, chip holder, system & method thereof
  • Flow-thru chip cartridge, chip holder, system & method thereof

Examples

Experimental program
Comparison scheme
Effect test

experiment 1

Uniform Fluid Distribution

[0109]Reproducible assay performance can be highly dependent on the uniformity of fluid distribution across the FTC (or chip) face. To test the uniformity of fluid flow, the inventors performed two different sets of experiments.

[0110]In a first experiment, a microarray pattern was spotted covering 60% of the viewable chip area. The array consisted of 16 identical 4×4 subarrays. Each subarray contained 4 different probes, denoted as probes 1-4 (P1-P4), spotted in quadruplicate. An image of the uniformity test array run through the FTC is shown in FIG. 12. In this experiment, a FTC cartridge had a test fluid delivery chamber that included a spade-like flow surface, such as flow surface 421 illustrated in FIGS. 3 and 4. The FTC cartridge had an α1-angle slope of 2.55°, an α2-angle slope of about 3.7-, and a trench β-angle of about 2.6°. The target mixture used to test the array contained targets complimentary to Probes 1, 2, and 3. The concentrations for targe...

experiment 2

In-Situ Detection

[0118]An advantage of the FTC cartridge and fluid delivery system of the present invention is that it permits observation and / or detection of reactions in-situ. For example, DNA hybridizations were monitored for fluorescently labeled targets in real-time by mounting the FTC cartridge of the present invention on an epi-fluorescence microscope. As sample passes through the chip, specific targets are captured from solution by the probes on the FTC. Under a re-circulation condition, target accumulates over time resulting in greater fluorescence intensity. In-situ detection of hybridization to the FTC was investigated using the FTC cartridge 300 described above with respect to Experiment 1. The cartridge was interfaced with a fluidics station embodying the features of the fluidics station 800 illustrated in FIG. 11. The cartridge was placed on the stage of a fluorescent microscope for the duration of the hybridization in order to allow in-situ detection. The FTC within t...

experiment 3

Temperature Control of Hybridization

[0121]By way of background, there is a significant interest in using DNA chips to determine single nucleotide polymorphisms (SNPs) for diagnostics. SNPs are single base mutations that can contribute to diseases. Mapping of SNPs is conventionally performed to determine the role in disease development and progression. Once determined, the SNP can be used as a diagnostic marker for testing individuals. Within the nucleic acid sequence homology, a successful discrimination between perfectly-matched (PM) and single base pair mismatch (SBMM) sequences is difficult to detect because of the requirement for control of test conditions, including temperature.

[0122]The ability to discriminate PM and SBMM sequences was investigated using the FTC cartridge 300 (as described above with respect to Experiment 1) by varying the temperature during hybridization for a series of PM and mismatch probes. FTCs were prepared with 3 different 18mer probes including a PM, S...

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Abstract

A system for performing hybridization assays comprises a cartridge for housing a flow through device, where the cartridge includes a test fluid chamber for facilitating a substantially uniform flow of a test fluid mixture through the flow through device, and a fluidics station to deliver the test fluid mixture to the cartridge. The cartridge has a chip holder that holds the flow-through device, which has an array of microchannel passages. The chip holder has a support for placement of the flow though device, the test fluid chamber for directing a substantially uniform flow of a test fluid mixture through the array of microchannel passages of the flow through device, and a first port that receives the test fluid mixture. The cartridge has a sealing system for preventing the leakage of the test fluid around the flow through device. The test fluid chamber is defined in part by a spade-like surface having an inlet for the test fluid mixture.

Description

[0001]The present application claims the benefit of the filing date of U.S. Provisional Application No. 60 / 171,510, filed on Dec. 22, 1999, which is hereby incorporated by reference in its entirety.BACKGROUND[0002]Microfabrication technology has revolutionized the electronics industry. This unleashed numerous industrial applications in miniaturization and automation of manufacturing processes. The impact of microfabrication technology in biomedical research can be seen in the growing presence of microprocessor-controlled analytical instrumentation and robotics in the laboratory, which is particularly evident in laboratories engaged in high throughput genome mapping and sequencing. One area of particular interest is the development and use of microfabricated genosensor devices for biomolecule analysis, such as a FLOW-THRU CHIP™ (“FTC”).[0003]Microfabricated genosensor devices are compact, but with a high density of components. Known microfabricated binding devices typically are recta...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C40B60/12B01L3/00B01L7/00B01L9/00G01N21/05G01N21/25G01N35/00
CPCB01L3/5027G01N2021/0346B01L3/502715B01L3/502746B01L7/00B01L7/52B01L9/527B01L2200/027B01L2200/0689B01L2300/0636B01L2300/0816B01L2300/0877B01L2300/18B01L2300/1822B01L2300/1838B01L2400/0478B01L2400/0481B01L2400/0487B01L2400/06B01L2400/0622G01N21/05G01N21/253G01N2035/00158B01L3/502707
Inventor GOODMAN, JACKTORRES, MATTHEWYANG, HONGJUNMATEER, DAVID G.SMITH, IAN STUART RICHARD
Owner GOODMAN JACK