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Interconnections of multiple perfused engineered tissue constructs and microbioreactors, multi-microformulators and applications of the same

An interconnected bus, biological technology, applied in the field of microfluidic systems, can solve problems such as cost constraints

Active Publication Date: 2017-08-08
VANDERBILT UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, this is done using automated fluid handling robots, but the size and cost of the robots and the requirement that a large number of well plates must be serviced by a single robot limits the number of combinations of growth factors etc. that can be detected

Method used

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  • Interconnections of multiple perfused engineered tissue constructs and microbioreactors, multi-microformulators and applications of the same
  • Interconnections of multiple perfused engineered tissue constructs and microbioreactors, multi-microformulators and applications of the same
  • Interconnections of multiple perfused engineered tissue constructs and microbioreactors, multi-microformulators and applications of the same

Examples

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Embodiment 1

[0161] Systems and methods for aseptic fluidic interconnection of multiple perfused engineered tissue constructs and microreactors

[0162] Some aspects of the present invention relate to systems and methods for aseptic fluid interconnection of multiple perfused engineered tissue constructs and microreactors, particularly the interconnection of integrated organ microfluidics (IOM) modules to create a human body-on-a-chip. In some embodiments, the present invention addresses the issues of sterilization, fluid containment, bubble generation, and excess volume associated with standard techniques for connecting organs using simple microfluidic channels or tubing. The novelty of the present invention is that the interconnection is arranged as a parallel circuit with cleaning line, arterial line, venous line and sewage line. The present invention has potential value for long-term culture of tissue engineered organ construction in any system or process, especially for processes that ...

Embodiment 2

[0219] Push-pull injectable microformulation module with multiple open reservoirs

[0220] The miniformulation module 100 shown above in Figures 1 and 17 is described in PCT Publication Nos. WO 2012 / 048261, WO 2013 / 086505, and WO 2014 / 081840, and is used to prepare and deliver custom formulations of cell culture media, including pharmaceuticals, Toxins and growth factors whose output is delivered to a single bioreactor, organ-on-a-chip or other fluidic reservoir, or a single set of such interconnected devices. The following describes how a computer-controlled microfluidic microformulation module, with additional computer-controlled valves and a fluid distribution and collection network, can be used to deliver solutions or mixtures of solutions independently or into multiple fluid reservoirs, such as for cell culture Well plates, multiple tissue or cell culture bioreactors or in different organs in a connected, in vitro organ-on-a-chip microphysiological system, and fluid is re...

Embodiment 3

[0308] Device for fluidic control between engineered tissue constructs, microreactors and well plates

[0309] This example discusses how the previously described invention can be modified and optimized for the control of fluids, as is specifically required for long-term cell culture in tissue chips or organ chips, which can be considered as two-dimensional or three-dimensional microreactions for culturing adherent or non-adherent cells with and without a supporting matrix.

[0310] When organ chips are connected together, there is a need for the missing endocrine organ system microscopic formulation design module, which can provide endocrine control for the above-mentioned integrated organ chip. Figure 36 A schematic of one such system comprising the neurovascular unit / blood-brain barrier, liver, kidney and skeletal muscle is shown. Control and sensing functions can be provided by different modules such as Figure 17 mentioned. For perspective, we are developing an in vit...

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Abstract

The invention relates to a system of fluidic valves and pumps and associated fluidic channels integratable into a bio-object microfluidics module. The module can include input and output buses; upstream and downstream interconnection bus control valves (CVs) coupled to the input and output buses, respectively. It may include arterial, venous, wash and waste bus lines, each connecting between the upstream and downstream interconnection bus CVs. It may also include an input CV connecting to the arterial bus line, upstream interconnection bus CV, bio-object and inlets, and an output CV connecting to the bio-object, input CV, downstream interconnection bus CV and outlets; and a pump connecting between the input CV and bio-object. The system of fluidic valves and pumps can be arranged to provide MicroFormulator functionality enabling precise mixtures of drugs, chemicals, or biochemicals to be delivered in a time-dependent fashion to biological entities housed in individual wells or chambers.

Description

[0001] Federally Funded Research Reports [0002] This invention is made under Contract No. W911NF-12-2-0036 awarded by the Defense Advanced Research Projects Agency, DTRA100271A-5196 and HDTRA1-09-1-00-13 awarded by the Defense Threat Reduction Agency, and by the National Institutes of Health 1UH2-TR000491-01 awarded by the Institute is supported by the government. The government has certain rights in this invention. [0003] Cross reference to related patent applications [0004] According to 35U. S. c. § 119(e), claimed by this application, U.S. Provisional Patent Application Serial Nos. 62 / 183571, 62 / 193029, 62 / 276047, and 62 / 295306, filed June 23, 2015, July 15, 2015, respectively Priority and related rights of patent applications filed on January 7, 2016 and February 15, 2016. Each of the above applications is incorporated herein by reference. [0005] This application is also US Patent Application Serial No. 13 / 877925, 14 / 363074, 14 / Continuation of application...

Claims

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Application Information

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IPC IPC(8): C12M3/00C12M1/36C12M1/34C12M1/00
CPCC12M21/08C12M23/16C12M29/10C12M41/48C12M23/04C12M23/40C12M23/44C12M23/58C12M41/46B01L3/502715B01L3/502738B01L2200/027B01L2200/028B01L2400/0622B01L2400/0644
Inventor 约翰·威克斯沃德米特里·马尔可夫菲利普·萨姆森弗兰克·布洛克大卫·谢弗罗纳德·雷萨勒
Owner VANDERBILT UNIV