Provided is a sample processing method that liquefies a medium solution by making a liquid that liquefies the medium solution act on a sample formed by gelating or solidifying the medium solution that is supported by a substrate while an observation subject is included therein, while maintaining a state in which the medium solution is supported by the substrate while the observation subject is included therein.

According to an aspect, the present description is related to an apparatus for depositing on a substrate drops of a specimen sample including a liquid medium and living microorganisms. The apparatus includes a tray for supporting the substrate, a container, e.g. a syringe, configured to receive a volume of the specimen sample and a drop deposition motor configured to push the specimen sample out of the container to form drops of a predetermined volume that detach by gravity and fall on the substrate. The apparatus further includes guiding motors configured for changing a relative position of the tray and the container and a control unit configured to synchronize the drop deposition motor and the guiding motors in order to deposit drops on the substrate according to a pattern.

Provided is a method for preparing a sample for microscope examination, the method including bringing a liquid (B) for gelling or solidifying a medium solution (A) into contact with a surface of the medium solution (A), which contains at least one spheroid (S) and which is substantially transparent when being gelled or solidified, in a state where the liquid (B) is in the form of mist, bubbles, or liquid droplets with a smaller volume than the volume of the medium solution (A), thereby gelling or solidifying the medium solution (A).

A method of making a cardiac construct is carried out by depositing a mixture comprising live mammalian cardiac cells (e.g., individual cells, organoids, or spheroids), fibrinogen, gelatin, and water on a support to form an intermediate cardiac construct; optionally co-depositing a structural support material (e.g., polycaprolactone) with the mixture in a configuration that supports the intermediate construct; and then contacting thrombin to the construct in an amount effective to cross-link the fibrinogen and produce a cardiac construct comprised of live cardiac cells that together spontaneously beat in a fibrin hydrogel. Constructs made and methods of using the same are also described.

Compositions and methods are provided that extend the range of biological assays, such as immunoassays. In one embodiment a plurality of discrete test sites are used. Data for the proportion of test sites that indicate the presence of the analyte of interest and data that provides a statistical value for a signal generated by the population of discrete test sites is gathered. The results of these digital and statistical approaches are aggregated to provide an extended dynamic range. In another embodiment two or more reagent additions are provided in a serial fashion to a single test site or vessel. Such additions present different reagent sets with different dilutions of the same sample, and permit simultaneous characterization of both high and low abundance analytes in a single multiplexed assay while avoiding the high dose hook effect observed for high abundance analytes at low sample dilutions. These approaches can be combined to provide further improvements in dynamic range.

The invention relates to a method for cultivating cells in adhesion culture, comprising at least the following steps: a) dissolving or suspending a cross-linkable, biocompatible material having adhesion points for cells in a cell culture medium; b) suspending cells in the cell culture medium, which contains the cross-linkable, biocompatible material, or in a medium that contains at least one component that is required for the cross-linking of the cross-linkable, biocompatible material; c) introducing the cell suspension into a medium in drops under conditions that initiate or permit the cross-linking of the biocompatible material, wherein either the cell suspension or the medium into which the cell suspension is introduced in drops contains the cross-linkable biocompatible material; d) forming stable, preferably porous capsules from cross-linked biocompatible material, which capsules contain incorporated adherent cells; e) proliferating the adherent cells in the capsules for a specified time period; f) breaking up the capsule material by means of a physical or chemical stimulus and releasing the cells as a cell suspension. In an especially preferred embodiment of the invention, the method is performed cyclically, in that the cells released in step f) are suspended anew in a cell culture medium that contains a cross-linkable, biocompatible material or in a medium that contains at least one component that is required for the cross-linking of the cross-linkable, biocompatible material and steps c)-f) are repeated at least once.

This invention provides devices and methods that enable co-incubation of microorganisms. Also provided are methods of making such devices for co-incubation of microorganisms, and various applications of such devices.

Provided is a sample manufacturing method that includes: a step of forming a hanging drop consisting of a liquid drop of a medium solution in a hanging state while causing at least one cell aggregate to be encapsulated in the liquid drop of the medium solution, the medium solution becoming substantially transparent upon gelling or solidifying; and a step of causing the hanging drop to gel or solidify by causing a promoting factor that promotes gelling or solidification of the medium solution to act on the hanging drop.

A method of making a cardiac construct is carried out by depositing a mixture comprising live mammalian cardiac cells (e.g., individual cells, organoids, or spheroids), fibrinogen, gelatin, and water on a support to form an intermediate cardiac construct; optionally co-depositing a structural support material (e.g., polycaprolactone) with the mixture in a configuration that supports the intermediate construct; and then contacting thrombin to the construct in an amount effective to cross-link the fibrinogen and produce a cardiac construct comprised of live cardiac cells that together spontaneously beat in a fibrin hydrogel. Constructs made and methods of using the same are also described.

A gel-encapsulated cell production apparatus according to an embodiment has a first droplet generator, a second droplet generator, and a gel-encapsulated cell generator. The first droplet generator generates a first droplet in which a processed cell is encapsulated. The second droplet generator generates a second droplet in which a gelator is encapsulated. The gel-encapsulated cell generator is connected to the first droplet generator and the second droplet generator via a channel, and the gel-encapsulated cell generator blends the first droplet and the second droplet and generates a gel-encapsulated cell, which is the cell encapsulated in a gel originating in the gelator.