Abstract: Methods of transferring material from a first device having an array of microwells to a second device is provided. In some examples, the first device and the second device are moved together toward a stopper plate and impinge on the stopper plate. In other examples, the first device and the second device are kept stationary and an impinging device is impacted on a mounting structure enclosing the first and second devices, causing material transfer from the microwells of the first device to the second device. Apparatus for carrying out the transfer of material is also disclosed.

Abstract: A kit includes a microfabricated device having a top surface defining an array of microwells for receiving a sample comprising at least one cell, and a membrane for applying on the top surface of the microfabricated device to retain the at least one cell in at least one microwell of the array of microwells after the sample is loaded on the microfabricated device.

Abstract: A method of screening for at least one biological entity of interest using a microfabricated device which has a top surface defining an array of microwells. A sample is loaded onto the microfabricated device such that at least one microwell of the array of microwells includes at least one cell and an amount of a nutrient. A membrane is applied to the microfabricated device to retain the at least one cell and the nutrient. A plurality of cells is cultured from the at least one cell in the at least one microwell of the array of microwells. The plurality of cells in the at least one microwell of the array of microwells are split into a first portion of the plurality of cells and a second portion of the plurality of cells. The plurality of cells is analyzed to determine a presence or absence of a biological entity of interest.

Abstract: A method of screening for at least one biological entity of interest using a microfabricated device which has a top surface defining an array of microwells. A sample is loaded onto the microfabricated device such that at least one microwell of the array of microwells includes at least one cell and an amount of a nutrient. A membrane is applied to the microfabricated device to retain the at least one cell and the nutrient. A plurality of cells are cultured from the at least one cell in the at least one microwell of the array of microwells. The plurality of cells is then analyzed to determine a presence or absence of a biological entity of interest.

Abstract: Methods of transferring material from a first device having an array of microwells to a second device is provided. In some examples, the first device and the second device are moved together toward a stopper plate and impinge on the stopper plate. In other examples, the first device and the second device are kept stationary and an impinging device is impacted on a mounting structure enclosing the first and second devices, causing material transfer from the microwells of the first device to the second device. Apparatus for carrying out the transfer of material is also disclosed.

Abstract: A microfabricated device defining a high density array of microwells is described for cultivating cells from a sample. A series of unique tags may be disposed in the microwells to identify one or more species of cells and locate the particular microwells in which each species was cultivated. A unique tag may be a nucleic acid molecule including a target-specific nucleotide sequence for annealing to a target nucleic acid fragment and a location-specific nucleotide sequence predetermined to identify one or more microwells. The device may be incubated to grow a plurality of cells, which may be split into an analysis portion and a reserve portion. High throughput methods are described for cultivating, screening, and determining a relative and/or absolute abundance of cells from a sample.

Abstract: Provided is a method of using a device including a plurality of microscale experimental units. At least one cell and an indicator capable of producing an optical signal are loaded in each of the plurality of experimental units. The device with the loaded contents is incubated to grow a plurality of cells. At least one optical property of the contents of each of the plurality of experimental units is measured at multiple time points during the incubation to thereby obtain a time-dependent profile. The time-dependent profile for the plurality of experimental units are analyzed, and the analysis result may be used to select/transfer contents from certain experimental unit(s) for further cultivation and/or assay, or to determine whether certain experimental units contain any biological entity of interest.

Abstract: A method is provided for analyzing a sample including a population of biological entities using at least one microfabricated device. A plurality of the microwells on the microfabricated device are each uniquely indexed, and loaded with a sample such that at least some microwells each include more than one cell of a biological entity. The microfabricated device was incubated at predetermined conditions, and a selected genetic material of the cells of the biological entities obtained from the incubation is amplified to obtaining amplicons. An aggregate of the amplicons are sequenced obtain sequencing data, based on which and the indexing of the microwells, an identification of the biological entities present in each of the plurality of microwells is obtained. Such identification can then be used to determine a relationship between different types of biological entities in the sample.

Abstract: A picking instrument for picking biological samples, such as microbial samples, includes a picking pin having a distal tip and three degrees-of-freedom and configured to move in x, y, and z directions. The picking instrument also includes a loading platform comprising a first area and a second area, the first area configured to accommodate and secure a microfabricated chip including a plurality of microwells. The picking pin is programmatically controlled to pick a sample contained in one or more selected microwells of the microfabricated chip and then transfer the sample to a predetermined location at the destination sample holder. Methods of operating the picking instrument, including calibrating the coordinates of the selected microwell(s) relative to a location of the picking pin, are also provided.

Abstract: A picking instrument for picking biological samples, such as microbial samples, includes a picking pin having a distal tip and three degrees-of-freedom and configured to move in x, y, and z directions. The picking instrument also includes a loading platform comprising a first area and a second area, the first area configured to accommodate and secure a microfabricated chip including a plurality of microwells. The picking pin is programmatically controlled to pick a sample contained in one or more selected microwells of the microfabricated chip and then transfer the sample to a predetermined location at the destination sample holder. Methods of operating the picking instrument, including calibrating the coordinates of the selected microwell(s) relative to a location of the picking pin, are also provided.

Abstract: A kit includes a microfabricated device having a top surface defining an array of microwells for receiving a sample comprising at least one cell, and a membrane for applying on the top surface of the microfabricated device to retain the at least one cell in at least one microwell of the array of microwells after the sample is loaded on the microfabricated device.

Abstract: A method of screening for at least one biological entity of interest using a microfabricated device which has a top surface defining an array of microwells. A sample is loaded onto the microfabricated device such that at least one microwell of the array of microwells includes at least one cell and an amount of a nutrient. A membrane is applied to the microfabricated device to retain the at least one cell and the nutrient. A plurality of cells is cultured from the at least one cell in the at least one microwell of the array of microwells. The plurality of cells in the at least one microwell of the array of microwells are split into a first portion of the plurality of cells and a second portion of the plurality of cells. The plurality of cells is analyzed to determine a presence or absence of a biological entity of interest.

Abstract: A method of screening for at least one biological entity of interest using a microfabricated device which has a top surface defining an array of microwells. A sample is loaded onto the microfabricated device such that at least one microwell of the array of microwells includes at least one cell and an amount of a nutrient. A membrane is applied to the microfabricated device to retain the at least one cell and the nutrient. A plurality of cells are cultured from the at least one cell in the at least one microwell of the array of microwells. The plurality of cells is then analyzed to determine a presence or absence of a biological entity of interest.

Abstract: A method of screening for at least one biological entity of interest using a microfabricated device which has a top surface defining an array of microwells. A sample is loaded onto the microfabricated device such that at least one microwell of the array of microwells includes at least one cell and an amount of a nutrient. A membrane is applied to the microfabricated device to retain the at least one cell and the nutrient. Without furnishing additional nutrient to the microwells, the microfabricated device is incubated to grow a plurality of cells from the at least one cell in the at least one microwell of the array of microwells. The plurality of cells is then analyzed to determine a presence or absence of a biological entity of interest.

Abstract: A picking instrument for picking biological samples, such as microbial samples, includes a picking pin having a distal tip and three degrees-of-freedom and configured to move in x, y, and z directions. The picking instrument also includes a loading platform comprising a first area and a second area, the first area configured to accommodate and secure a microfabricated chip including a plurality of microwells. The picking pin is programmatically controlled to pick a sample contained in one or more selected microwells of the microfabricated chip and then transfer the sample to a predetermined location at the destination sample holder. Methods of operating the picking instrument, including calibrating the coordinates of the selected microwell(s) relative to a location of the picking pin, are also provided.

Abstract: A method of screening for at least one biological entity of interest using a microfabricated device which has a top surface defining an array of microwells. A sample is loaded onto the microfabricated device such that at least one microwell of the array of microwells includes at least one cell and an amount of a nutrient. A membrane is applied to the microfabricated device to retain the at least one cell and the nutrient. Without furnishing additional nutrient to the microwells, the microfabricated device is incubated to grow a plurality of cells from the at least one cell in the at least one microwell of the array of microwells. The plurality of cells is then analyzed to determine a presence or absence of a biological entity of interest.

Abstract: A method for selecting a medium is provided. The method includes obtaining a microfabricated device including a plurality of microwells; loading a plurality of different media into the plurality of microwells such that each microwell of the plurality comprises a medium and the plurality of microwells comprises a plurality of different media; loading at least one cell from a sample into each microwell of the plurality microwells; incubating the microfabricated device at a predetermined condition for a predetermined duration of time; comparing the contents of the plurality of microwells across the plurality of microwells; and based on the comparison, determining at least one medium out of the plurality of different media.

Abstract: A method is provided for analyzing a sample including a population of biological entities using at least one microfabricated device. A plurality of the microwells on the microfabricated device are each uniquely indexed, and loaded with a sample such that at least some microwells each include more than one cell of a biological entity. The microfabricated device was incubated at predetermined conditions, and a selected genetic material of the cells of the biological entities obtained from the incubation is amplified to obtaining amplicons. An aggregate of the amplicons are sequenced obtain sequencing data, based on which and the indexing of the microwells, an identification of the biological entities present in each of the plurality of microwells is obtained. Such identification can then be used to determine a relationship between different types of biological entities in the sample.

Abstract: A microfabricated device defining a high density array of microwells is described for cultivating cells from a sample. A series of unique tags may be disposed in the microwells to identify one or more species of cells and locate the particular microwells in which each species was cultivated. A unique tag may be a nucleic acid molecule including a target-specific nucleotide sequence for annealing to a target nucleic acid fragment and a location-specific nucleotide sequence predetermined to identify one or more microwells. The device may be incubated to grow a plurality of cells, which may be split into an analysis portion and a reserve portion. High throughput methods are described for cultivating, screening, and determining a relative and/or absolute abundance of cells from a sample.