Abstract: Described herein are cell culture methods of producing hepatocytes, or mature, highly functional hepatocyte-like cells in vitro; cell culture media suitable for use in these methods; functional hepatocytes, or mature, highly functional hepatocyte-like cells produced by these methods; and cell compositions comprising hepatocytes, or mature, highly functional hepatocyte-like cells produced by these methods.

Abstract: A method and system of delivering a charged cargo, such as a biomolecule, to a target structure, such as cells, exosomes, other vesicles or micelles, using an electroactive porous membrane. This method comprises contacting an electroactive porous membrane with a fluid flow toward the membrane. The fluid contains charged biomolecules and the membrane and biomolecules are oppositely charged so that the biomolecules in the fluid are trapped on the membrane as the fluid flows through the pores of the membrane. Acceptor cells of interest are pinned to the membrane by the flow of the fluid, thereby aggregating the cells onto the membrane in close proximity to the trapped biomolecules. Finally, the acceptor cells are permeabilized.

Abstract: A system and method of using a microfluidic electroporation device for cell treatment is provided. The cell or exosome treatment system can include a microfluidic electroporation device, a voltage source coupled to a plurality of electrodes and a controller coupled to the voltage source. The microfluidic electroporation device can include a fluid receptacle, a semipermeable membrane, and a base including a channel in fluid communication with the fluid receptacle and the semipermeable membrane. A first electrode can be positioned within the fluid receptacle and a second electrode coupled to the base. The second electrode is positioned relative to the first electrode to create an electric field sufficient to electroporate cells or exosomes disposed in the fluid receptacle. The controller can be configured to cause the first and second electrodes to apply voltage electroporating the cells and exosomes.

Abstract: The methods and systems described herein provide a cell culture platform with an array of tissue modeling environments and dynamic control of fluid flow. The cell culture platform includes an array of wells that are fluidically coupled by microchannel structures. The dynamically controlled flow of fluid interacts with cells grown within the microchannels.

Abstract: Compression cold welding methods, joint structures, and hermetically sealed containment devices are provided. The method includes providing a first substrate having at least one first joint structure which comprises a first joining surface, which surface comprises a first metal; providing a second substrate having at least one second joint structure which comprises a second joining surface, which surface comprises a second metal; and compressing together the at least one first joint structure and the at least one second joint structure to locally deform and shear the joining surfaces at one or more interfaces in an amount effective to form a metal-to-metal bond between the first metal and second metal of the joining surfaces. Overlaps at the joining surfaces are effective to displace surface contaminants and facilitate intimate contact between the joining surfaces without heat input. Hermetically sealed devices can contain drug formulations, biosensors, or MEMS devices.

Abstract: A destroy on-demand electrical device includes a substrate layer formed using a soluble material (e.g., a Germanium oxide), a semi-conductor layer formed from a material that can become soluble upon further processing (e.g., Germanium) and conductive elements, formed from a metallic material such as Copper. The device is coupled with one or more disintegration sources that contain disintegration agents (e.g., Hydrogen Peroxide) that can promote disintegration of the device. The device can be destroyed in response to actuation of the disintegration sources, for example by actuation of a source that produces Hydrogen Peroxide for use in oxidizing the semi-conductor layer. Water can be used to dissolve dissolvable substrate layers. The semi-conductor layer can be destroyed by first processing this layer to form a dissolvable material and dissolving the processed layer with water. The remaining Copper components disintegrate once their underlying layer have been dissolved and/or by use of a salt.

Abstract: Drug delivery devices are provided that are configured to release drug following passive or active activation of the device protecting the drug contained therein. In one aspect, the device may be configured to release a drug following selective application of light irradiation to the device. In another aspect, the device is configured to a release drug following degradation of at least a part of the device body that is formed, for example, from a bioerodible, hermetic material. An exemplary bioerodible, hermetic material is a biodegradable glass. Still other aspects provide for release of a drug upon a combination of both passive and active activation of the device.

Abstract: Devices and methods are provided for selectively delivering a drug by laser activation. The device includes structural elements forming a hermetic, enclosed reservoir, and at least one drug unit contained in the enclosed reservoir. The at least one drug unit includes a drug. The device is able to absorb laser irradiation effective to open the enclosed reservoir to permit release of the drug. The method includes implanting a drug delivery device into a tissue site of a patient, and irradiating at least a portion of the drug delivery device to breach the enclosed reservoir to permit the drug to be released in tissues at the tissue site.

Abstract: Methods and systems are provided for making a drug microtablet. The method includes loading a lyophilization capillary channel with a liquid drug solution; lyophilizing the liquid drug solution in the lyophilization capillary channel to produce a lyophilized drug formulation; compressing the lyophilized drug formulation in the lyophilization capillary channel, or in a compression capillary channel, to form a microtablet; and ejecting the microtablet from the lyophilization capillary channel or compression capillary channel. The methods and systems may provide drug microtablets having improved content uniformity and reduced weight variability.

Abstract: Sensor devices and methods are provided for detecting the presence or concentration of an analyte in fluid. The device has a reservoir; a working electrode located within the reservoir, a catalyst covering at least part of the working electrode; an oxygen-generating auxiliary electrode in the reservoir; and a reservoir cap to isolate the working and auxiliary electrodes within the reservoir. The device further includes means for selectively rupturing the cap to permit analyte from outside the reservoir to contact the catalyst. The methods may include in vivo glucose monitoring and may include implanting the device in a patient; disintegrating a reservoir cap to permit glucose to enter the reservoir; generating oxygen using the oxygen-generating auxiliary electrode; and using a working electrode to oxidize hydrogen peroxide produced by the reaction of the oxygen with glucose in the presence of glucose oxidase, and thereby detecting endogenous glucose in the patient.

Abstract: Devices, such as medical devices, are provided which include a body portion having at least one reservoir which has two or more openings, the two or more openings being defined in part by a reservoir cap support; reservoir contents, such as a drug formulation or sensor, disposed inside the reservoir; and a reservoir cap which closes off the two or more reservoir openings. The reservoir cap, which can be ruptured, controls release or exposure of the reservoir contents. In one embodiment, the device is an implantable medical device and provides for the controlled release of drug or exposure of a sensor.

Abstract: Methods and systems are provided for making a drug microtablet. The method includes loading a lyophilization capillary channel with a liquid drug solution; lyophilizing the liquid drug solution in the lyophilization capillary channel to produce a lyophilized drug formulation; compressing the lyophilized drug formulation in the lyophilization capillary channel, or in a compression capillary channel, to form a microtablet; and ejecting the microtablet from the lyophilization capillary channel or compression capillary channel. The methods and systems may provide drug microtablets having improved content uniformity and reduced weight variability.

Abstract: Compression cold welding methods, joint structures, and hermetically sealed containment devices are provided. The method includes providing a first substrate having at least one first joint structure which comprises a first joining surface, which surface comprises a first metal; providing a second substrate having at least one second joint structure which comprises a second joining surface, which surface comprises a second metal; and compressing together the at least one first joint structure and the at least one second joint structure to locally deform and shear the joining surfaces at one or more interfaces in an amount effective to form a metal-to-metal bond between the first metal and second metal of the joining surfaces. Overlaps at the joining surfaces are effective to displace surface contaminants and facilitate intimate contact between the joining surfaces without heat input. Hermetically sealed devices can contain drug formulations, biosensors, or MEMS devices.

Abstract: Methods and systems are provided for making a drug microtablet. The method includes loading a lyophilization capillary channel with a liquid drug solution; lyophilizing the liquid drug solution in the lyophilization capillary channel to produce a lyophilized drug formulation; compressing the lyophilized drug formulation in the lyophilization capillary channel, or in a compression capillary channel, to form a microtablet; and ejecting the microtablet from the lyophilization capillary channel or compression capillary channel. The methods and systems may provide drug microtablets having improved content uniformity and reduced weight variability.

Abstract: Compression cold welding methods, joint structures, and hermetically sealed containment devices are provided. The method includes providing a first substrate having at least one first joint structure which comprises a first joining surface, which surface comprises a first metal; providing a second substrate having at least one second joint structure which comprises a second joining surface, which surface comprises a second metal; and compressing together the at least one first joint structure and the at least one second joint structure to locally deform and shear the joining surfaces at one or more interfaces in an amount effective to form a metal-to-metal bond between the first metal and second metal of the joining surfaces. Overlaps at the joining surfaces are effective to displace surface contaminants and facilitate intimate contact between the joining surfaces without heat input. Hermetically sealed devices can contain drug formulations, biosensors, or MEMS devices.

Abstract: An implantable drug delivery device that uses multiple reservoir elements to contain and release doses of active pharmaceutical ingredients. The device includes a first shell element, which has a first enclosed cavity volume and forms a low-permeability barrier. The first shell element is configured to absorb light irradiation from a laser source, the laser irradiation causing a breach in the first shell element. A first active pharmaceutical ingredient is contained in the first enclosed cavity volume and is released when the first shell element is breached. The device also includes a second shell element, which has a second enclosed cavity volume and also forms a low-permeability barrier. A second active pharmaceutical ingredient is contained in the second enclosed cavity volume. The device also includes an envelope element containing the first and second shell elements.

Abstract: Devices, such as medical devices, are provided which include a body portion having at least one reservoir which has two or more openings, the two or more openings being defined in part by a reservoir cap support; reservoir contents, such as a drug formulation or sensor, disposed inside the reservoir; and a reservoir cap which closes off the two or more reservoir openings. The reservoir cap, which can be ruptured, controls release or exposure of the reservoir contents. In one embodiment, the device is an implantable medical device and provides for the controlled release of drug or exposure of a sensor.

Abstract: Reservoir-based devices are provided in which an individual reservoir has at least two openings with a support structure therebetween and closed by reservoir caps covering the openings to control release or exposure of reservoir contents. In one embodiment, the device is an implantable medical device and provides for the controlled release of drug or exposure of a sensor. The device includes a substrate; at least one reservoir disposed in the substrate, the reservoir having two or more openings; reservoir contents located in the reservoir; two or more discrete reservoir caps, each reservoir cap sealingly covering at least one of the reservoir openings; and control means for selectively disintegrating or permeabilizing the reservoir caps.

Abstract: Devices and methods are provided for controlled release of chemical molecules, such as drugs. One device comprises a plurality of reservoirs; a rupturable covering, such as a thin metal film, enclosing a first end of each reservoir; a release formulation in each reservoir comprising chemical molecules for release; an expanding material layer in each reservoir; and a semi-permeable membrane enclosing a second end of each reservoir distal the release formulation, the semi-permeable membrane being operable to permit selected molecules (e.g., water) from outside the reservoir to diffuse to the expanding material layer to expand the expanding material layer and displace the release formulation in an amount effective rupture the rupturable membrane and discharge the release formulation.

Abstract: A technique for fabricating the required surface shapes for micro optical elements, such as curved micro mirrors and lenses, starts with a simple, binary for example, approximation to the desired surface shape. Then polishing, e.g., chemical mechanical polishing (CMP), is used to form the smooth optical surface. Specifically, starting with a mesa or blind hole, with a mesa profile, a smooth mirror or lens structure is fabricated.