Abstract
In this study, we present a novel approach for the design and development of three-dimensional monolithic ceramic microsystems with complex geometries and with potential applications in the biomedical field, mainly linked to labs-on-chips and organs-on-chips. The microsystem object of study stands out for its having a complex three-dimensional geometry, for being obtained as a single integrated element, hence reducing components, preventing leakage and avoiding post-processes, and for having a cantilever porous ceramic membrane aimed at separating cell culture chambers at different levels, which imitates the typical configuration of transwell assays. The design has been performed taking account of the special features of the manufacturing technology and includes ad hoc incorporated supporting elements, which do not affect overall performance, for avoiding collapse of the cantilever ceramic membrane during debinding and sintering. The manufacture of the complex three-dimensional microsystem has been accomplished by means of lithography-based ceramic manufacture, the additive manufacturing technology which currently provides the most appealing compromises between overall part size and precision when working with ceramic materials. The microsystem obtained provides one of the most remarkable examples of monolithic bio-microsystems and, to our knowledge, a step forward in the field of ceramic microsystems with complex geometries for lab-on-chip and organ-on-chip applications. Cell culture results help to highlight the potential of the proposed approach and the adequacy of using ceramic materials for biological applications and for interacting at a cellular level.
Highlights
Global health concerns require new ways of modeling and studying diseases and of assessing related therapies in a rapid and non-invasive way, all of which has promoted a growing demand of biomedical microdevices aimed at culturing different cell types, at learning from their mutual interactions and at applying such knowledge to the development of more efficient and realistic biomimetic platforms for modeling medical conditions and for drug testing [1]
Cell culture results help to highlight the potential of the proposed approach and the adequacy of using ceramic materials for biological applications and for interacting at a cellular level
We have presented a very promising approach for the design and development of three-dimensional monolithic ceramic biomedical microsystems with complex geometries and with potential applications in fields linked to labs-onchips and organs-on-chips
Summary
Global health concerns require new ways of modeling and studying diseases and of assessing related therapies in a rapid and non-invasive way, all of which has promoted a growing demand of biomedical microdevices aimed at culturing different cell types, at learning from their mutual interactions and at applying such knowledge to the development of more efficient and realistic biomimetic platforms for modeling medical conditions and for drug testing [1]. State-of-the-art cell co-culture devices and platforms include modified Petri dishes with some areas prepared for locating a cell-loaded gel amidst fluid; “Flocell®” devices with micro-perforated tubes placed in a bottle and loaded with saline solution; and, more frequently, “Transwell®” devices, consisting of a glass with a porous-membrane bottom placed inside a larger glass, again filled with buffer In these transwell and flocell devices, different cell types can interact in a physiological way through the tube or membrane pores. The already mentioned devices are in many cases excessively complex, made of several parts manufactured separately, too large for the phenomena being studied and inadequate from the perspective of ecoefficient product development, making them more “chips on a lab” than “labs on a chip” [3] Their sizes promote the use of high quantities of cells and reagents, many of which are extremely difficult and expensive to obtain, limiting the implementation of systematic studies
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