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. The device may be incubated to grow a plurality of cells, which may be split into an analysis portion and a reserve portion. Methods are provided for screening a biological entity of interest using the microfabricated device, for example, for screening phosphate solubilizing bacteria or other bacteria producing acids.

Abstract: A method of transferring material using a picking pin having a distal tip includes: forming a first coating of organic molecules on at least a portion of the distal tip of the picking pin; dipping at least a portion of the coated distal tip in a first source such that an amount of material is picked up from the first source and attached to the first coating; dipping the coated distal tip attached with the amount of material into a first target so as to release some of the amount of the material to the first target; and removing the first coating from the distal tip. The procedure can be repeated for transferring additional material from the same or different source to the same or different targets.

Abstract: A method for identifying a status of at least one cell in a cell culture including resorufin in an anaerobic atmosphere is provided. In the method, the extent of reduction of resorufin in the cell culture to dihyrdoresorufin is measured while the cell culture is maintained in an anaerobic atmosphere. The cell culture may be loaded in microwells of a microfabricated chip positioned in an anaerobic chamber, and the measurement can be based on fluorescence of the cell culture.

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: A microfabricated device defining a high density array of microwells is described for cultivating cells from a sample. The device may be incubated to grow a plurality of cells, which may be split into an analysis portion and a reserve portion. Methods are provided for screening a biological entity of interest using the microfabricated device, for example, for screening phosphate solubilizing bacteria or other bacteria producing acids.

Abstract: A system for loading a sample into microwells of a microfabricated chip. The system can include a vacuum loading module, and can further include a sealing module. The loading module includes enclosed chamber formed a bottom part and a top part. The chamber is provided with at least one vacuum port. The chamber can also be provided with an injection port for injecting a liquid sample into the chamber to thereby load the sample into the microwells of the microchip. The sealing module includes a wheel carrying a sealing film and a mounting platform to position a microfabricated chip, where the rotation of the wheel on the microfabricated chip transfers the sealing film on the top surface of the microfabricated chip. Methods of loading a sample onto the microfabricated chip and sealing the loaded chip are also provided.

Abstract: A method of screening for at least one biological entity of interest in a sample using a microfabricated chip having an array of microwells. At least one cell from the sample and a nutrient are loaded into at least one microwell, and a gas permeable membrane is applied to the microfabricated device to retain the at least one cell. The microfabricated device is incubated to grow a plurality of cells. Mass spectrometry is used to detect gas in a sampling region for the at least one microwell. A presence or absence of at least one biological entity of interest in the at least one microwell is determined based on the detection.

Abstract: A method of modifying a microfabricated chip made of a hydrophobic material is provided. The microfabricated chip has a top surface including a plurality of microwells each having a bottom and a side wall, and interstitial space between the microwells. First, the ed chip is surface treated to render the surface of the bottom and side wall of the microwells and the interstitial space hydrophilic. Then, the surface of the interstitial space is treated to render it hydrophobic. A microfabricated chip having hydrophilic microwells and hydrophobic interstitial space is also provided.

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 method of transferring material from a first microfabricated device to a second microfabricated device. At least one magnetic bead is loaded into at least one microwell of the first microfabricated device, where a plurality of cells are cultivated. The second microfabricated device is positioned such that the at least one microwell of the first array of microwells is aligned with at least one microwell of the second array of microwells. A magnetic field is applied so as to move the at least one magnetic bead contained in the at least one microwell of the first microfabricated device into the at least one microwell of the second microfabricated device. In this manner, at least one cell from the plurality of cells in the at least one microwell of the first microfabricated device is transferred to the at least one microwell of the second microfabricated device.

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 for providing a lateral flow of liquid across a plurality of microwells of a microfabricated device. The microwells of the microfabricated device are covered by a membrane which includes a first portion disposed on one side of at least one microwell and a second portion on the other side of the at least one microwell. The first portion of the membrane is contacted with a liquid absorbable by the membrane such that the liquid is wicked by the membrane and laterally flows from the first portion to the second portion and across the at least one microwell. At least a portion of the liquid enters the at least one microwell.

Abstract: A method of transferring material from a first microfabricated device to a second microfabricated device. At least one magnetic bead is loaded into at least one microwell of the first microfabricated device, where a plurality of cells are cultivated. The second microfabricated device is positioned such that the at least one microwell of the first array of microwells is aligned with at least one microwell of the second array of microwells. A magnetic field is applied so as to move the at least one magnetic bead contained in the at least one microwell of the first microfabricated device into the at least one microwell of the second microfabricated device. In this manner, at least one cell from the plurality of cells in the at least one microwell of the first microfabricated device is transferred to the at least one microwell of the second microfabricated device.