Hanging drop devices, systems and/or methods

a technology of devices and droplets, applied in the field of hanging drop devices, systems and/or methods, can solve the problems of time-consuming and expensive nature of drug studies involving such models, inability to produce accurate readouts, and inability to perform in vitro in the manner of conventional two-dimensional studies, etc., and achieve the effect of high throughpu

Inactive Publication Date: 2014-06-26
3D BIOMATRIX +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

Enables the formation of uniformly sized spheroids in a high-throughput manner, with stable geometry and long-term culture capabilities, reducing labor and costs, and providing accurate therapeutic readouts comparable to in vivo models.

Problems solved by technology

Currently, however, most in vitro studies are still performed under conventional two-dimensional (2D) cell culture systems, which are often not physiological models for functional tissues and tumors.
Therefore, drug studies involving such models may not produce accurate readouts.
However, one obvious drawback of in vivo studies is the time-consuming and expensive nature of these experiments.
As a result, the drops are susceptible to perturbation, resulting in falling, spreading, and merging with neighboring drops.
Although inexpensive, this method is labor-intensive, does not permit efficient scalable production, and is not compatible with automated instruments for high-throughput screening.
Because it is difficult to perform media exchange without damaging the spheroids, this method usually requires another labor-intensive step of transferring the spheroids manually, one by one, to a multi-well culture plate for longer-term culture, treatment, analysis, and harvest.
This method requires the consumption of large quantities of culture media.
It also requires specialized equipment and the size and uniformity of the spheroids are hard to control.
The high variability in spheroids prohibits their use in many applications.
However, these methods require specialized and expensive equipment for generating the microwell structures and micropatterns.
Moreover, since a plurality of spheroids is cultured within one fluid compartment, the spheroids cannot be individually monitored, manipulated, and treated with testing compounds.
The difficulty of performing analysis on individual spheroids before and after treatment also makes these methods unsuitable for certain applications, for example, drug testing and screening applications.
However, these devices are expensive to design and produce.
In addition, these devices are not suitable for long-term culture of spheroids, not chemically compatible with certain drugs, and not compatible with automated instruments for performing high-throughput screening.

Method used

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  • Hanging drop devices, systems and/or methods
  • Hanging drop devices, systems and/or methods
  • Hanging drop devices, systems and/or methods

Examples

Experimental program
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example 2

Additional Plate Design

[0132]The devices of certain embodiments of the present disclosure are able to robustly generate hanging drops, maintain hanging drops, provide the ability to add and / or remove fluid from the hanging drops, or combinations thereof. Because each access hole is configured to hold a hanging drop securely in place, large numbers of hanging drops can be formed reproducibly. In certain embodiments, each access hole is substantially identical. The access holes which have openings on the top surface of the array plate allow fluids to be withdrawn or added to form hanging drops or to already formed hanging drops. This means fluids can be withdrawn or added throughout an experiment to manipulate and / or maintain measurable properties of the hanging drops and / or the contents in said hanging drops. This example describes a device (for example as described in FIG. 14) that provides an extra topographical barrier to confine the droplets stably. The barrier is shown in FIG. 1...

example 3

[0135]This Example provides examples of methods, systems and devices that further illustrate certain non-limiting embodiments of the present disclosure:

example 1

comprising:

[0136]a) at least one array plate, the at least one array plate comprising a top surface and a bottom surface and a plurality of holes therein, wherein each of the plurality of holes comprises a top and a bottom and wherein the bottom surface of said array plate comprises a at least one plateau substantially adjacent to the bottom of at least one of the plurality of holes; and

[0137]b) wherein the at least one array plate is configured to accommodate a plurality of hanging drops, wherein each drop hangs from a corresponding one of the plurality of said holes and extends beneath the hole, wherein the number of hanging drops the that at least one array plate can accommodate is equal to or less than the number of holes in the at least one array plate.

2. The system of example 1, further comprising at least one second plate positioned below said at least one array plate.

3. The system of examples 1 or 2, wherein said at least one array plate further comprises at least one reserv...

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Abstract

The present disclosure relates general to devices, systems, and methods of using such devices in creating and handling hanging drops of fluid. The present disclosure also relates to cell culture devices, methods and / or systems of using such devices as well as the use of cell culture devices, for example, for research and high throughput screening.

Description

[0001]This application is a continuation of U.S. application Ser. No. 13 / 575,558, which is a national phase application under 35 U.S.C. ยง371 of PCT International Application No. PCT / US2011 / 022966, filed Jan. 28, 2011, which claims priority to U.S. provisional application 61 / 299,011, filed Jan. 28, 2010, each of which are herein incorporated by reference in its entirety. In addition, the following manual entitled Sambrook, J. et al., Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, New York (1989) pp. 16.9-16.15 is herein incorporated by reference in its entirety.FIELD[0002]The present disclosure relates generally to devices, systems, and methods of using such devices in creating and handling hanging drops of fluid. The present disclosure also relates generally to cell culture devices, systems and methods of using such devices. The present disclosure also relates generally to the use of cell culture devices for research and high throughput screeni...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): C12M1/12C12N5/00
CPCB01L3/50853B01L3/50857B01L3/5088B01L2200/025B01L2200/141B01L2200/142B01L2300/0829B01L2300/161G01N2035/1046C12M23/12G01N35/028B33Y80/00C12M25/01C12N5/0062
InventorTAKAYAMA, SHUICHITUNG, YI-CHUNGHSIAO, AMY YU-CHINGJAN, EDWARD
Owner3D BIOMATRIX