Patent Application
20210107015
Analytical Ultracentrifuge (AUC) instruments are centrifuges known for generating sedimentation data that can be deconvoluted for the determination of size distribution profiles in protein and other biological samples, for the purpose of evaluating the extent of aggregates or other impurities in fluid samples. An early example is disclosed in U.S. Pat. No. 1,648,369 the content of which is incorporated herein by reference, wherein the fundamental components of an AUC instrument are described in detail. Later examples include U.S. Pat. Nos. 2,340,825, 3,391,597, 3,487,994, and 4,226,537, the content of each being incorporated herein by reference, which present improvements to AUC instrument design and the introduction of improved supporting devices, including the AUC cell, which is assembled and inserted into specialized rotors that allow data collection via modules within the centrifuge.
A standard procedure for the operation of a conventional AUC instrument and its accessory hardware components is to first assemble the AUC cell, which is a layered collection of windows, sector-shaped sample chamber, and outer housing and screw rings. Specifically, a sector-shaped geometry is defined as the volume element of a cylindrical segment having the cross-sectional area of a circular sector (an area enclosed by two radii of a large circle, the bounding arc of the larger circle between the radii, and an arc of a smaller concentric circle of lesser radius). Once torqued so as to render the sample chamber fluid-tight, the fluid sample may be loaded into the chamber through small ports, which are also subsequently sealed. The AUC cell is placed into a rotor which is typically solid titanium with cylindrical cavities parallel to the axis of rotation and arranged symmetrically about said axis of rotation. The rotor is placed inside the AUC instrument and allowed to equilibrate to the desired temperature via thermostatting of the centrifuge chamber, controlled by refrigeration or heating elements which are located inside the centrifuge. The centrifuge is also programmed to accelerate the rotor to the desired centrifugal velocity and maintain the velocity for a fixed period.
Embodiments relate to centrifugation, and, more specifically, to analytical centrifugation or ultracentrifugation systems and methods for detecting in fluid samples the degree of sedimentation of soluble molecules, aggregates, or particles. In some embodiments, detection can be performed in real time and continuously. In some embodiments, detection can be performed during the course of the sedimentation process. Some embodiments provide for an assembly of modules or sub-units for sample containment, illumination and detection. In some embodiments, supporting functions are integrated and confined within the geometry of a rotor. In some embodiments, supporting functions of the sample interrogation, data generation and data collection, as well as modulation and control of sample condition, are integrated into units, and, in some embodiments, assembled into structures, or cells that are affixed within the rotor. The resulting configuration can be rotated by an externally applied centrifugal force, such as that supplied by a standard floor-model centrifuge, ultracentrifuge, or table-top centrifuge, which are commonly available. In some embodiments, the resulting self-contained, integrated device can generate, store, and transmit data for completing an analytical centrifugation or ultracentrifugation experiment.
In an aspect, a rotor system, comprises: a rotor constructed and arranged to rotate about an axis of rotation; a source of electromagnetic radiation at a first position of the rotor, the source of electromagnetic radiation configured to emit electromagnetic radiation at one or more wavelengths; a sample region; and a detector at a second position of the rotor, the detector constructed and arranged to receive electromagnetic radiation that traverses at least a portion of the sample region.
In an embodiment, the rotor comprises a central opening.
In an embodiment, the central opening is aligned with the axis of rotation.
In an embodiment, the rotor is constructed and arranged to mate with a spindle.
In an embodiment, the spindle is aligned with the axis of rotation.
In an embodiment, the spindle comprises a spindle of a centrifuge.
In an embodiment, the rotor is oriented symmetrically about the axis of rotation.
In an embodiment, the rotor comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation.
In an embodiment, neighboring ones of the one or more stacked sub-units are coupled to each other at a threaded interface.
In an embodiment, one or more of the one or more stacked sub-units are coupled with a bolt-through configuration.
In an embodiment, a gasket is positioned between one or more of the one or more stacked sub-units.
In an embodiment, the gasket is constructed and arranged to form a sealed region.
In an embodiment, the sealed region is sealed from an ambient region external to the sealed region.
In an embodiment, one or more of the one or more sub-units are coupled to each other with a tongue-in-groove structure.
In an embodiment, one or more of the one or more stacked sub-units comprise high-strength materials.
In an embodiment, the high-strength material comprises titanium.
In an embodiment, the high-strength material comprises an alloy material.
In an embodiment, the high-strength material comprises a composite material.
In an embodiment, the high-strength material comprises a material including a carbon fiber material.
In an embodiment, the sample region comprises a sector shape.
In an embodiment, the sample region comprises a sample chamber.
In an embodiment, the sample chamber comprises a removable liner.
In an embodiment, the first position and the second position are at the sample chamber and wherein the sample chamber comprises the source of electromagnetic radiation and the detector.
In an embodiment, the sample region comprises an open top and an open bottom.
In an embodiment, the sample region is coupled to one or more neighboring sub-units.
In an embodiment, a portion of the electromagnetic radiation emitted from the source of electromagnetic radiation is incident on the detector.
In an embodiment, the electromagnetic radiation is directed toward the sample region.
In an embodiment, the detector is arranged to detect electromagnetic radiation that traverses a portion of the sample region.
In an embodiment, the sample region, the source of electromagnetic radiation, and the detector are arranged along an axis that is parallel to the axis of rotation.
In an embodiment, the source of electromagnetic radiation is positioned at a first of the one or more stacked sub-units.
In an embodiment, the sample region is positioned at a second of the one or more stacked sub-units.
In an embodiment, the detector is positioned at a third of the one or more stacked sub-units.
In an embodiment, the system further comprises an alignment mechanism that aligns the first, second and third of the one or more stacked sub-units so that the source of electromagnetic radiation, the sample region and the detector being aligned in a vertical direction along an axis of interrogation that is parallel to the axis of rotation.
In an embodiment, a portion of the electromagnetic radiation emitted from the source of electromagnetic radiation traverses a portion of the sample chamber.
In an embodiment, one or more wavelengths of the electromagnetic radiation is incident at the sample region.
In an embodiment, electromagnetic radiation propagates through the sample region to the detector.
In an embodiment, electromagnetic radiation triggers a reaction of material at the sample region.
In an embodiment, the detector collects electromagnetic radiation emitted from the sample region and the electromagnetic radiation emitted from the sample region comprises one or more wavelengths that are different than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the wavelengths of the electromagnetic radiation emitted from the sample region are greater than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the wavelengths of the electromagnetic radiation emitted from the sample region are less than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the electromagnetic radiation triggers a photophysical interaction.
In an embodiment, the photophysical interaction comprises excitation of molecules present in the sample region to energy levels above a ground state of the sample molecules.
In an embodiment, the excitation of the energy levels consists of at least one of excitation of electronic energy levels, excitation of vibrational energy levels or excitation of rotational energy levels.
In an embodiment, the source of electromagnetic radiation is one of a plurality of sources of electromagnetic radiation that is optically coupled with the detector.
In an embodiment, the source of electromagnetic radiation is coupled to a circuit board.
In an embodiment, the rotor comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein a topmost sub-unit of the one or more sub-units comprises a source of electromagnetic radiation coupled to a circuit board.
In an embodiment, the rotor comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein a topmost sub-unit of the one or more sub-units comprises a plurality of sources of electromagnetic radiation, wherein the sample region comprises a plurality of sample regions and wherein the detector comprises a plurality of detectors, each source of electromagnetic radiation being optically coupled to a corresponding detector through an optical path that includes a corresponding sample region.
In an embodiment, the source of electromagnetic radiation is a single light emitting diode (LED).
In an embodiment, the source of electromagnetic radiation comprises an array of light emitting diodes (LEDs).
In an embodiment, the source of electromagnetic radiation comprises a laser diode.
In an embodiment, the source of electromagnetic radiation comprises and array of laser diodes.
In an embodiment, the detector comprises an array detector.
In an embodiment, the detector comprises a point detector.
In an embodiment, the detector comprises a CCD array.
In an embodiment, the detector comprises a photodiode.
In an embodiment, the detector periodically samples incident electromagnetic radiation.
In an embodiment, the system further comprises a storage that stores information collected by the detector.
In an embodiment, the system further comprises a transmitter that transmits the stored information stored by the storage to a receiver.
In an embodiment, the transmitter transmits the stored information as the rotor is rotating about the axis of rotation.
In an embodiment, the system transmits the stored information when the rotor is stationary.
In an embodiment, the system is configured to measure light absorbance of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide spectroscopic information of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide hyperspectral image data of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide Schlieren images of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide fluorescence images of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide quantitative fluorescence emission data of the sample region based on the stored information collected by the detector.
In an embodiment, the quantitative fluorescence emission data comprises a spatial arrangement of the sample region.
In an embodiment, the system further comprises a Fabry-Perot interferometer optically coupled with the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical filters positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical lenses positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more mirrors positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical diffusers positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical collimators positioned between the source of electromagnetic radiation and the detector.
In an embodiment, one or more of the one or more optical collimators comprises at least one self-collimating photonic crystal.
In an embodiment, one or more of the one or more optical collimators comprises at least one micro-Fresnel lens.
In an embodiment, the system further comprises one or more optical lenses positioned between the source of electromagnetic radiation and the detector wherein the one or more optical lenses are positioned relative to the sample region and the detector such that the detector detects an image of a plane at the sample region.
In an embodiment, the one or more lenses are positioned below the sample region.
In an embodiment, the system further comprises an elongated edge constructed and arranged to block a portion of the light incident on the detector.
In an embodiment, the system further comprises an iris constructed and arranged to block a portion of the light incident on the detector.
In an embodiment, the system further comprises a beamsplitter system constructed and arranged to direct electromagnetic radiation from the source of electromagnetic radiation to a plurality of locations.
In an embodiment, the beamsplitter system comprises at least one mirror.
In an embodiment, the beamsplitter system comprises at least one filter.
In an embodiment, the beamsplitter system comprises at least one lens.
In an embodiment, the beamsplitter system is constructed and arranged such that electromagnetic radiation emitted from a first sub-unit of the rotor is optically coupled to a detector on a second sub-unit of the rotor different than the first sub-unit.
In an embodiment, the rotor comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein one or more of the one or more stacked sub-units are electrically connected with one or more connectors.
In an embodiment, the one or more connectors are configured to transfer information.
In an embodiment, the one or more connectors are configured to transfer power.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with USB ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with micro-USB ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with VGA ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with D-type connectors.
In an embodiment, the system further comprises a transmitter configured to transmit information from the detector.
In an embodiment, the transmitter is configured to transmit the information in an encrypted format.
In an embodiment, the transmitter is configured to transmit the information to a cloud-based storage system.
In an embodiment, the transmitter is configured to transmit information wirelessly.
In an embodiment, the transmitter comprises an antenna.
In an embodiment, the transmitter is configured to transmit the information optically.
In an embodiment, the transmitter comprises a cable connection.
In an embodiment, the cable connection comprises an electrical connection.
In an embodiment, the cable connection comprises fiber optics.
In an embodiment, the cable connection comprises connection to a circuit board.
In an embodiment, the cable connection comprises connection to an on-board memory.
In an embodiment, the on-board memory comprises a device selected from the group consisting of: a random access memory (RAM) device, a read-only memory (ROM) device, a solid-state memory (SSD) device, an SD memory card, or a micro-SD memory card.
In an embodiment, the transmitter is positioned at a bottom portion of the rotor.
In an embodiment, the rotor comprises a central opening aligned with the axis of rotation.
In an embodiment, the transmitter is constructed and arranged to extend through the central opening.
In an embodiment, the transmitter extends from the bottom of the rotor to the top of the rotor.
In an embodiment, the transmitter comprises one of a plurality of transmitters.
In an embodiment, the transmitter comprises a battery.
In an embodiment, the system further comprises a recharging mechanism that recharges the battery, the recharging mechanism converting rotational energy from the rotation of the rotor into electrical current.
In an embodiment, the recharging mechanism comprises an electric generator comprising a planetary gear configuration constructed and arranged to facilitate relative internal rotation in a rotor-stator pairing.
In an embodiment, the system further comprises an on-board memory at the rotor.
In an embodiment, the on-board memory comprises a device selected from the group consisting of: a random access memory (RAM) device, a read-only memory (ROM) device, a solid-state memory (SSD) device, an SD memory card, or a micro-SD memory card.
In an embodiment, the system further comprises a temperature control system configured to modify a temperature of the sample region.
In an embodiment, the temperature control system is configured to maintain the temperature of the sample region.
In an embodiment, maintaining the temperature comprises heating the sample region.
In an embodiment, maintaining the temperature comprises cooling the sample region.
In an embodiment, the temperature control system circulates thermally conductive material at the sample region.
In an embodiment, the temperature control system comprises a pumping system to circulate the thermally conductive material.
In an embodiment, the temperature control system heats the sample region.
In an embodiment, the temperature control system cools the sample region.
In an embodiment, the temperature control system circulates thermally conductive material through channels at one or more sub-units of the rotor.
In an embodiment, the system further comprises a temperature sensor, and wherein the temperature control system adjusts the temperature of the sample region in response to an output of the temperature sensor.
In an embodiment, the temperature sensor comprises a thermocouple.
In an embodiment, the temperature sensor comprises an optical sensor.
In an embodiment, the temperature sensor comprises an infrared sensor.
In an embodiment, the temperature sensor is one of a plurality of temperature sensors.
In an embodiment, at least two of the plurality of temperature sensors are in communication with each other.
In an embodiment, the temperature control system comprises an open-loop temperature system.
In an embodiment, the temperature control system comprises a closed-loop temperature feedback system.
In an embodiment, the system further comprises a sample chamber at the sample region and wherein the temperature control system is configured to adjust a temperature of the sample chamber.
In an embodiment, the temperature control system is positioned at the sample region.
In an embodiment, the temperature control system comprises a thermoelectric or Peltier device.
In an embodiment, the rotor comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein one or more of the one or more stacked sub-units comprises a power source.
In an embodiment, the power source comprises at least one battery.
In an embodiment, the at least one battery is positioned on a first sub-unit and supplies power to a device on a second sub-unit.
In an embodiment, each of the one or more sub-units comprises a power source.
In an embodiment, the power source comprises a recharging mechanism constructed and arranged to convert the rotational energy of the rotor into electrical current.
In an embodiment, the recharging mechanism comprises at least one voltaic cell.
In an embodiment, the at least one voltaic cell comprises two electrodes separated by an electrolyte solution.
In an embodiment, the current is driven by an electrolyte concentration difference in the electrolyte solution that is induced by centrifugation.
In an embodiment, the at least one voltaic cell comprises a concentration cell.
In an embodiment, the at least one voltaic cell is driven by a radio-isotopic decay.
In an embodiment, the at least one voltaic cell comprises a beta-voltaic cell.
In an embodiment, the system further comprises a recharging mechanism that recharges the battery, the recharging mechanism converting rotational energy from the rotation of the rotor into electrical current.
In an embodiment, the recharging mechanism comprises an electric generator comprising a planetary gear configuration constructed and arranged to facilitate relative internal rotation in a rotor-stator pairing.
In another aspect, an integrated rotor system, comprises: a rotor comprising at least one rotor cavity, the rotor being constructed and arranged to rotate about an axis of rotation; and an interrogation cell positioned in the at least one rotor cavity. The interrogation cell comprises: a source of electromagnetic radiation at a first position of the interrogation cell, the source of electromagnetic radiation configured to emit electromagnetic radiation at one or more wavelengths; a sample region; and a detector at a second position of the interrogation cell, the detector configured to receive electromagnetic radiation that traverses at least a portion of the sample region.
In an embodiment, the at least one rotor cavity comprises a plurality of rotor cavities.
In an embodiment, the system further comprises a plurality of interrogation cells, each interrogation cell corresponding to one of the plurality of rotor cavities.
In an embodiment, the rotor comprises a central opening.
In an embodiment, the central opening is aligned with the axis of rotation.
In an embodiment, the rotor is constructed and arranged to mate with a spindle.
In an embodiment, the spindle is aligned with the axis of rotation.
In an embodiment, the spindle comprises a spindle of a centrifuge.
In an embodiment, the rotor is oriented symmetrically about the axis of rotation.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation.
In an embodiment, neighboring ones of the one or more stacked sub-units are coupled to each other at a threaded interface.
In an embodiment, one or more of the one or more stacked sub-units are coupled with a bolt-through configuration.
In an embodiment, a gasket is positioned between one or more of the one or more stacked sub-units.
In an embodiment, the gasket is constructed and arranged to form a sealed region.
In an embodiment, the sealed region is sealed from an ambient region external to the sealed region.
In an embodiment, one or more of the one or more sub-units are coupled to each other with a tongue-in-groove structure.
In an embodiment, one or more of the one or more stacked sub-units comprise high-strength materials.
In an embodiment, the high-strength material comprises titanium.
In an embodiment, the high-strength material comprises an alloy material.
In an embodiment, the high-strength material comprises a composite material.
In an embodiment, the high-strength material comprises a material including a carbon fiber material.
In an embodiment, the sample region comprises a sector shape.
In an embodiment, the sample region comprises a sample chamber.
In an embodiment, the sample chamber comprises a removable liner.
In an embodiment, the first position and the second position are at the sample chamber and wherein the sample chamber comprises the source of electromagnetic radiation and the detector.
In an embodiment, the sample region comprises an open top and an open bottom.
In an embodiment, the sample region is coupled to one or more neighboring sub-units.
In an embodiment, a portion of the electromagnetic radiation emitted from the source of electromagnetic radiation is incident on the detector.
In an embodiment, the electromagnetic radiation is directed toward the sample region.
In an embodiment, the detector is arranged to detect electromagnetic radiation that traverses a portion of the sample region.
In an embodiment, the sample region, the source of electromagnetic radiation, and the detector are arranged along an axis that is parallel to the axis of rotation.
In an embodiment, the source of electromagnetic radiation is positioned at a first of the one or more stacked sub-units.
In an embodiment, the sample region is positioned at a second of the one or more stacked sub-units.
In an embodiment, the detector is positioned at a third of the one or more stacked sub-units.
In an embodiment, the system further comprises an alignment mechanism that aligns the first, second and third of the one or more stacked sub-units so that the source of electromagnetic radiation, the sample region and the detector being aligned in a vertical direction along an axis of interrogation that is parallel to the axis of rotation.
In an embodiment, a portion of the electromagnetic radiation emitted from the source of electromagnetic radiation traverses a portion of the sample chamber.
In an embodiment, one or more wavelengths of the electromagnetic radiation is incident at the sample region.
In an embodiment, electromagnetic radiation propagates through the sample region to the detector.
In an embodiment, electromagnetic radiation triggers a reaction of material at the sample region.
In an embodiment, the detector collects electromagnetic radiation emitted from the sample region and the electromagnetic radiation emitted from the sample region comprises one or more wavelengths that are different than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the wavelengths of the electromagnetic radiation emitted from the sample region are greater than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the wavelengths of the electromagnetic radiation emitted from the sample region are less than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the electromagnetic radiation triggers a photophysical interaction.
In an embodiment, the photophysical interaction comprises excitation of molecules present in the sample region to energy levels above a ground state of the sample molecules.
In an embodiment, the excitation of the energy levels consists of at least one of excitation of electronic energy levels, excitation of vibrational energy levels or excitation of rotational energy levels.
In an embodiment, the source of electromagnetic radiation is one of a plurality of sources of electromagnetic radiation that is optically coupled with the detector.
In an embodiment, the source of electromagnetic radiation is coupled to a circuit board.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein a topmost sub-unit of the one or more sub-units comprises a source of electromagnetic radiation coupled to a circuit board.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein a topmost sub-unit of the one or more sub-units comprises a plurality of sources of electromagnetic radiation, wherein the sample region comprises a plurality of sample regions and wherein the detector comprises a plurality of detectors, each source of electromagnetic radiation being optically coupled to a corresponding detector through an optical path that includes a corresponding sample region.
In an embodiment, the source of electromagnetic radiation is a single light emitting diode (LED).
In an embodiment, the source of electromagnetic radiation comprises an array of light emitting diodes (LEDs).
In an embodiment, the source of electromagnetic radiation comprises a laser diode.
In an embodiment, the source of electromagnetic radiation comprises and array of laser diodes.
In an embodiment, the detector comprises an array detector.
In an embodiment, the detector comprises a point detector.
In an embodiment, the detector comprises a CCD array.
In an embodiment, the detector comprises a photodiode.
In an embodiment, the detector periodically samples incident electromagnetic radiation.
In an embodiment, the system further comprises a storage that stores information collected by the detector.
In an embodiment, the system further comprises a transmitter that transmits the stored information stored by the storage to a receiver.
In an embodiment, the transmitter transmits the stored information as the rotor is rotating about the axis of rotation.
In an embodiment, the system transmits the stored information when the rotor is stationary.
In an embodiment, the system is configured to measure light absorbance of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide spectroscopic information of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide hyperspectral image data of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide Schlieren images of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide fluorescence images of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide quantitative fluorescence emission data of the sample region based on the stored information collected by the detector.
In an embodiment, the quantitative fluorescence emission data comprises a spatial arrangement of the sample region.
In an embodiment, the system further comprises a Fabry-Perot interferometer optically coupled with the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical filters positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical lenses positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more mirrors positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical diffusers positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical collimators positioned between the source of electromagnetic radiation and the detector.
In an embodiment, one or more of the one or more optical collimators comprises at least one self-collimating photonic crystal.
In an embodiment, one or more of the one or more optical collimators comprises at least one micro-Fresnel lens.
In an embodiment, the system further comprises one or more optical lenses positioned between the source of electromagnetic radiation and the detector wherein the one or more optical lenses are positioned relative to the sample region and the detector such that the detector detects an image of a plane at the sample region.
In an embodiment, the one or more lenses are positioned below the sample region.
In an embodiment, the system further comprises an elongated edge constructed and arranged to block a portion of the light incident on the detector.
In an embodiment, the system further comprises an iris constructed and arranged to block a portion of the light incident on the detector.
In an embodiment, the system further comprises a beamsplitter system constructed and arranged to direct electromagnetic radiation from the source of electromagnetic radiation to a plurality of locations.
In an embodiment, the beamsplitter system comprises at least one mirror.
In an embodiment, the beamsplitter system comprises at least one filter.
In an embodiment, the beamsplitter system comprises at least one lens.
In an embodiment, the beamsplitter system is constructed and arranged such that electromagnetic radiation emitted from a first sub-unit of the interrogation cell is optically coupled to a detector on a second sub-unit of the interrogation cell different than the first sub-unit.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein one or more of the one or more stacked sub-units are electrically connected with one or more connectors.
In an embodiment, the one or more connectors are configured to transfer information.
In an embodiment, the one or more connectors are configured to transfer power.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with USB ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with micro-USB ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with VGA ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with D-type connectors.
In an embodiment, the system further comprises a transmitter configured to transmit information from the detector.
In an embodiment, the transmitter is configured to transmit the information in an encrypted format.
In an embodiment, the transmitter is configured to transmit the information to a cloud-based storage system.
In an embodiment, the transmitter is configured to transmit information wirelessly.
In an embodiment, the transmitter comprises an antenna.
In an embodiment, the transmitter is configured to transmit the information optically.
In an embodiment, the transmitter comprises a cable connection.
In an embodiment, the cable connection comprises an electrical connection.
In an embodiment, the cable connection comprises fiber optics.
In an embodiment, the cable connection comprises connection to a circuit board.
In an embodiment, the cable connection comprises connection to an on-board memory.
In an embodiment, the on-board memory comprises a device selected from the group consisting of: a random access memory (RAM) device, a read-only memory (ROM) device, a solid-state memory (SSD) device, an SD memory card, or a micro-SD memory card.
In an embodiment, the transmitter is positioned at a bottom portion of the interrogation cell.
In an embodiment, the rotor comprises a central opening aligned with the axis of rotation.
In an embodiment, the transmitter is constructed and arranged to extend through the central opening.
In an embodiment, the transmitter extends from the bottom of the rotor to the top of the rotor.
In an embodiment, the transmitter comprises one of a plurality of transmitters.
In an embodiment, the transmitter comprises a battery.
In an embodiment, the system further comprises a recharging mechanism that recharges the battery, the recharging mechanism converting rotational energy from the rotation of the rotor into electrical current.
In an embodiment, the recharging mechanism comprises an electric generator comprising a planetary gear configuration constructed and arranged to facilitate relative internal rotation in a rotor-stator pairing.
In an embodiment, the system further comprises an on-board memory at the interrogation cell.
In an embodiment, the on-board memory comprises a device selected from the group consisting of: a random access memory (RAM) device, a read-only memory (ROM) device, a solid-state memory (SSD) device, an SD memory card, or a micro-SD memory card.
In an embodiment, the system further comprises a temperature control system configured to modify a temperature of the sample region.
In an embodiment, the temperature control system is configured to maintain the temperature of the sample region.
In an embodiment, maintaining the temperature comprises heating the sample region.
In an embodiment, maintaining the temperature comprises cooling the sample region.
In an embodiment, the temperature control system circulates thermally conductive material at the sample region.
In an embodiment, the temperature control system comprises a pumping system to circulate the thermally conductive material.
In an embodiment, the temperature control system heats the sample region.
In an embodiment, the temperature control system cools the sample region.
In an embodiment, the temperature control system circulates thermally conductive material through channels at one or more sub-units of the interrogation cell.
In an embodiment, the system further comprises a temperature sensor, and wherein the temperature control system adjusts the temperature of the sample region in response to an output of the temperature sensor.
In an embodiment, the temperature sensor comprises a thermocouple.
In an embodiment, the temperature sensor comprises an optical sensor.
In an embodiment, the temperature sensor comprises an infrared sensor.
In an embodiment, the temperature sensor is one of a plurality of temperature sensors.
In an embodiment, at least two of the plurality of temperature sensors are in communication with each other.
In an embodiment, the temperature control system comprises an open-loop temperature system.
In an embodiment, the temperature control system comprises a closed-loop temperature feedback system.
In an embodiment, the system further comprises a sample chamber at the sample region and wherein the temperature control system is configured to adjust a temperature of the sample chamber.
In an embodiment, the temperature control system is positioned at the sample region.
In an embodiment, the temperature control system comprises a thermoelectric or Peltier device.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein one or more of the one or more stacked sub-units comprises a power source.
In an embodiment, the power source comprises at least one battery.
In an embodiment, the at least one battery is positioned on a first sub-unit and supplies power to a device on a second sub-unit.
In an embodiment, each of the one or more sub-units comprises a power source.
In an embodiment, the power source comprises a recharging mechanism constructed and arranged to convert the rotational energy of the rotor into electrical current.
In an embodiment, the recharging mechanism comprises at least one voltaic cell.
In an embodiment, the at least one voltaic cell comprises two electrodes separated by an electrolyte solution.
In an embodiment, the current is driven by an electrolyte concentration difference in the electrolyte solution that is induced by centrifugation.
In an embodiment, the at least one voltaic cell comprises a concentration cell.
In an embodiment, the at least one voltaic cell is driven by a radio-isotopic decay.
In an embodiment, the at least one voltaic cell comprises a beta-voltaic cell.
In an embodiment, the system further comprises a recharging mechanism that recharges the battery, the recharging mechanism converting rotational energy from the rotation of the rotor into electrical current.
In an embodiment, the recharging mechanism comprises an electric generator comprising a planetary gear configuration constructed and arranged to facilitate relative internal rotation in a rotor-stator pairing.
In another aspect, an interrogation cell, comprises; a source of electromagnetic radiation at a first position, the source of electromagnetic radiation configured to emit electromagnetic radiation at one or more wavelengths; a sample region; and a detector at a second position, the detector configured to receive electromagnetic radiation that traverses at least a portion of the sample region, wherein the interrogation cell is dimensioned for positioning in a rotor cavity of a centrifuge rotor.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation.
In an embodiment, neighboring ones of the one or more stacked sub-units are coupled to each other at a threaded interface.
In an embodiment, one or more of the one or more stacked sub-units are coupled with a bolt-through configuration.
In an embodiment, a gasket is positioned between one or more of the one or more stacked sub-units.
In an embodiment, the gasket is constructed and arranged to form a sealed region.
In an embodiment, the sealed region is sealed from an ambient region external to the sealed region.
In an embodiment, one or more of the one or more sub-units are coupled to each other with a tongue-in-groove structure.
In an embodiment, one or more of the one or more stacked sub-units comprise high-strength materials.
In an embodiment, the high-strength material comprises titanium.
In an embodiment, the high-strength material comprises an alloy material.
In an embodiment, the high-strength material comprises a composite material.
In an embodiment, the high-strength material comprises a material including a carbon fiber material.
In an embodiment, the sample region comprises a sector shape.
In an embodiment, the sample region comprises a sample chamber.
In an embodiment, the sample chamber comprises a removable liner.
In an embodiment, the first position and the second position are at the sample chamber and wherein the sample chamber comprises the source of electromagnetic radiation and the detector.
In an embodiment, the sample region comprises an open top and an open bottom.
In an embodiment, the sample region is coupled to one or more neighboring sub-units.
In an embodiment, a portion of the electromagnetic radiation emitted from the source of electromagnetic radiation is incident on the detector.
In an embodiment, the electromagnetic radiation is directed toward the sample region.
In an embodiment, the detector is arranged to detect electromagnetic radiation that traverses a portion of the sample region.
In an embodiment, the sample region, the source of electromagnetic radiation, and the detector are arranged along an axis that is parallel to the axis of rotation.
In an embodiment, the source of electromagnetic radiation is positioned at a first of the one or more stacked sub-units.
In an embodiment, the sample region is positioned at a second of the one or more stacked sub-units.
In an embodiment, the detector is positioned at a third of the one or more stacked sub-units.
In an embodiment, the system further comprises an alignment mechanism that aligns the first, second and third of the one or more stacked sub-units so that the source of electromagnetic radiation, the sample region and the detector being aligned in a vertical direction along an axis of interrogation that is parallel to the axis of rotation.
In an embodiment, a portion of the electromagnetic radiation emitted from the source of electromagnetic radiation traverses a portion of the sample chamber.
In an embodiment, one or more wavelengths of the electromagnetic radiation is incident at the sample region.
In an embodiment, electromagnetic radiation propagates through the sample region to the detector.
In an embodiment, electromagnetic radiation triggers a reaction of material at the sample region.
In an embodiment, the detector collects electromagnetic radiation emitted from the sample region and the electromagnetic radiation emitted from the sample region comprises one or more wavelengths that are different than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the wavelengths of the electromagnetic radiation emitted from the sample region are greater than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the wavelengths of the electromagnetic radiation emitted from the sample region are less than the one or more wavelengths emitted from the source of electromagnetic radiation.
In an embodiment, the electromagnetic radiation triggers a photophysical interaction.
In an embodiment, the photophysical interaction comprises excitation of molecules present in the sample region to energy levels above a ground state of the sample molecules.
In an embodiment, the excitation of the energy levels consists of at least one of excitation of electronic energy levels, excitation of vibrational energy levels or excitation of rotational energy levels.
In an embodiment, the source of electromagnetic radiation is one of a plurality of sources of electromagnetic radiation that is optically coupled with the detector.
In an embodiment, the source of electromagnetic radiation is coupled to a circuit board.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein a topmost sub-unit of the one or more sub-units comprises a source of electromagnetic radiation coupled to a circuit board.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein a topmost sub-unit of the one or more sub-units comprises a plurality of sources of electromagnetic radiation, wherein the sample region comprises a plurality of sample regions and wherein the detector comprises a plurality of detectors, each source of electromagnetic radiation being optically coupled to a corresponding detector through an optical path that includes a corresponding sample region.
In an embodiment, the source of electromagnetic radiation is a single light emitting diode (LED).
In an embodiment, the source of electromagnetic radiation comprises an array of light emitting diodes (LEDs).
In an embodiment, the source of electromagnetic radiation comprises a laser diode.
In an embodiment, the source of electromagnetic radiation comprises and array of laser diodes.
In an embodiment, the detector comprises an array detector.
In an embodiment, the detector comprises a point detector.
In an embodiment, the detector comprises a CCD array.
In an embodiment, the detector comprises a photodiode.
In an embodiment, the detector periodically samples incident electromagnetic radiation.
In an embodiment, the system further comprises a storage that stores information collected by the detector.
In an embodiment, the system further comprises a transmitter that transmits the stored information stored by the storage to a receiver.
In an embodiment, the transmitter transmits the stored information as the interrogation cell is rotating about the axis of rotation of the rotor.
In an embodiment, the system transmits the stored information when the interrogation cell is stationary.
In an embodiment, the system is configured to measure light absorbance of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide spectroscopic information of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide hyperspectral image data of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide Schlieren images of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide fluorescence images of the sample region based on the stored information collected by the detector.
In an embodiment, the system is configured to provide quantitative fluorescence emission data of the sample region based on the stored information collected by the detector.
In an embodiment, the quantitative fluorescence emission data comprises a spatial arrangement of the sample region.
In an embodiment, the system further comprises a Fabry-Perot interferometer optically coupled with the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical filters positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical lenses positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more mirrors positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical diffusers positioned between the source of electromagnetic radiation and the detector.
In an embodiment, the system further comprises one or more optical collimators positioned between the source of electromagnetic radiation and the detector.
In an embodiment, one or more of the one or more optical collimators comprises at least one self-collimating photonic crystal.
In an embodiment, one or more of the one or more optical collimators comprises at least one micro-Fresnel lens.
In an embodiment, the system further comprises one or more optical lenses positioned between the source of electromagnetic radiation and the detector wherein the one or more optical lenses are positioned relative to the sample region and the detector such that the detector detects an image of a plane at the sample region.
In an embodiment, the one or more lenses are positioned below the sample region.
In an embodiment, the system further comprises an elongated edge constructed and arranged to block a portion of the light incident on the detector.
In an embodiment, the system further comprises an iris constructed and arranged to block a portion of the light incident on the detector.
In an embodiment, the system further comprises a beamsplitter system constructed and arranged to direct electromagnetic radiation from the source of electromagnetic radiation to a plurality of locations.
In an embodiment, the beamsplitter system comprises at least one mirror.
In an embodiment, the beamsplitter system comprises at least one filter.
In an embodiment, the beamsplitter system comprises at least one lens.
In an embodiment, the beamsplitter system is constructed and arranged such that electromagnetic radiation emitted from a first sub-unit of the interrogation cell is optically coupled to a detector on a second sub-unit of the interrogation cell different than the first sub-unit.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein one or more of the one or more stacked sub-units are electrically connected with one or more connectors.
In an embodiment, the one or more connectors are configured to transfer information.
In an embodiment, the one or more connectors are configured to transfer power.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with USB ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with micro-USB ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with VGA ports.
In an embodiment, one or more of the one or more stacked sub-units are electrically connected with D-type connectors.
In an embodiment, the system further comprises a transmitter configured to transmit information from the detector.
In an embodiment, the transmitter is configured to transmit the information in an encrypted format.
In an embodiment, the transmitter is configured to transmit the information to a cloud-based storage system.
In an embodiment, the transmitter is configured to transmit information wirelessly.
In an embodiment, the transmitter comprises an antenna.
In an embodiment, the transmitter is configured to transmit the information optically.
In an embodiment, the transmitter comprises a cable connection.
In an embodiment, the cable connection comprises an electrical connection.
In an embodiment, the cable connection comprises fiber optics.
In an embodiment, the cable connection comprises connection to a circuit board.
In an embodiment, the cable connection comprises connection to an on-board memory.
In an embodiment, the on-board memory comprises a device selected from the group consisting of: a random access memory (RAM) device, a read-only memory (ROM) device, a soli-state memory (SSD) device, an SD memory card, or a micro-SD memory card.
In an embodiment, the transmitter is positioned at a bottom portion of the interrogation cell.
In an embodiment, the transmitter comprises one of a plurality of transmitters.
In an embodiment, the transmitter comprises a battery.
In an embodiment, the system further comprises an on-board memory at the interrogation cell.
In an embodiment, the on-board memory comprises a device selected from the group consisting of: a random access memory (RAM) device, a read-only memory (ROM) device, a solid-state memory (SSD) device, an SD memory card, or a micro-SD memory card.
In an embodiment, the system further comprises a temperature control system configured to modify a temperature of the sample region.
In an embodiment, the temperature control system is configured to maintain the temperature of the sample region.
In an embodiment, maintaining the temperature comprises heating the sample region.
In an embodiment, maintaining the temperature comprises cooling the sample region.
In an embodiment, the temperature control system circulates thermally conductive material at the sample region.
In an embodiment, the temperature control system comprises a pumping system to circulate the thermally conductive material.
In an embodiment, the temperature control system heats the sample region.
In an embodiment, the temperature control system cools the sample region.
In an embodiment, the temperature control system circulates thermally conductive material through channels at one or more sub-units of the interrogation cell.
In an embodiment, the system further comprises a temperature sensor, and wherein the temperature control system adjusts the temperature of the sample region in response to an output of the temperature sensor.
In an embodiment, the temperature sensor comprises a thermocouple.
In an embodiment, the temperature sensor comprises an optical sensor.
In an embodiment, the temperature sensor comprises an infrared sensor.
In an embodiment, the temperature sensor is one of a plurality of temperature sensors.
In an embodiment, at least two of the plurality of temperature sensors are in communication with each other.
In an embodiment, the temperature control system comprises an open-loop temperature system.
In an embodiment, the temperature control system comprises a closed-loop temperature feedback system.
In an embodiment, the system further comprises a sample chamber at the sample region and wherein the temperature control system is configured to adjust a temperature of the sample chamber.
In an embodiment, the temperature control system is positioned at the sample region.
In an embodiment, the temperature control system comprises a thermoelectric or Peltier device.
In an embodiment, the interrogation cell comprises one or more sub-units configured to be stacked in a vertical direction of extension along the axis of rotation and wherein one or more of the one or more stacked sub-units comprises a power source.
In an embodiment, the power source comprises at least one battery.
In an embodiment, the at least one battery is positioned on a first sub-unit and supplies power to a device on a second sub-unit.
In an embodiment, each of the one or more sub-units comprises a power source.
In an embodiment, the power source comprises a recharging mechanism constructed and arranged to convert the rotational energy of the interrogation cell into electrical current.
In an embodiment, the recharging mechanism comprises at least one voltaic cell.
In an embodiment, the at least one voltaic cell comprises two electrodes separated by an electrolyte solution.
In an embodiment, the current is driven by an electrolyte concentration difference in the electrolyte solution that is induced by centrifugation.
In an embodiment, the at least one voltaic cell comprises a concentration cell.
In an embodiment, the at least one voltaic cell is driven by a radio-isotopic decay.
In an embodiment, the at least one voltaic cell comprises a beta-voltaic cell.
In an embodiment, the system further comprises a recharging mechanism that recharges the battery, the recharging mechanism converting rotational energy from the rotation of the interrogation cell into electrical current.
In an aspect, a method comprises: providing a rotor constructed and arranged to rotate about an axis of rotation; providing a source of electromagnetic radiation at a first position of the rotor, the source of electromagnetic radiation configured to emit electromagnetic radiation at one or more wavelengths; providing a sample region; and providing a detector at a second position of the rotor, the detector constructed and arranged to receive electromagnetic radiation that traverses at least a portion of the sample region.
In an embodiment, the method further comprises mounting the rotor system at a centrifuge.
In an aspect, a method comprises: providing a rotor comprising at least one rotor cavity, the rotor being constructed and arranged to rotate about an axis of rotation; and providing an interrogation cell positioned in the at least one rotor cavity, comprising: providing a source of electromagnetic radiation at a first position of the interrogation cell, the source of electromagnetic radiation configured to emit electromagnetic radiation at one or more wavelengths; providing a sample region; and providing a detector at a second position of the interrogation cell, the detector configured to receive electromagnetic radiation that traverses at least a portion of the sample region.
In an embodiment, the method further comprises mounting the rotor system at a centrifuge.
In an aspect, a method of providing an interrogation cell, comprises: providing a source of electromagnetic radiation, the source of electromagnetic radiation configured to emit electromagnetic radiation at one or more wavelengths; providing a sample region; and providing a detector at a second position, the detector configured to receive electromagnetic radiation that traverses at least a portion of the sample region, wherein the interrogation cell is dimensioned for positioning in a rotor cavity of a centrifuge rotor.
In an embodiment, the method further comprises mounting the interrogation cell at a centrifuge rotor.
In an embodiment, the method further comprises mounting the centrifuge rotor including the interrogation cell at a centrifuge.
The foregoing and other objects, features and advantages of embodiments of the present inventive concepts will be apparent from the more particular description of embodiments, as illustrated in the accompanying drawings in which like reference characters refer to the same elements throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the embodiments.
FIG. 8G1 is a close-up perspective view of an embodiment of a functional element and an associated connector, in accordance with aspects of the present inventive concepts.
FIG. 8H1 is a perspective view of an embodiment of the two subunits of FIG. 8F1, in accordance with aspects of the present inventive concepts.
FIG. 8H2 is a perspective view of an embodiment of the two subunits of FIG. 8F1 coupled with an air-tight and liquid-tight junction, in accordance with aspects of the present inventive concepts.
FIG. 8H3 is a perspective view of a sample being added to the sample region, in accordance with aspects of the present inventive concepts.
FIG. 8H4 is a perspective view of an embodiment of a subunit being added above the sample region, in accordance with aspect of the present inventive concepts.
FIG. 8H5 is a perspective view of an embodiment of three subunits coupled together, in accordance with aspects of the present inventive concepts.
FIG. 11C1 is a close-up perspective view of an embodiment of one or more illumination elements 70 at a position at a source subunit, in accordance with aspects of the present inventive concepts.
FIG. 11D1 is a perspective view of an embodiment of sources of electromagnetic radiation, in accordance with aspects of the present inventive concepts.
FIG. 11D2 is a perspective view of an embodiment of sources of electromagnetic radiation, in accordance with aspects of the present inventive concepts.
FIG. 11F1 is a close-up perspective view of an embodiment of one or more detection elements, in accordance with aspects of the present inventive concepts.
FIG. 11G1 is a perspective view of an embodiment of a rotor system comprising a Schlieren image detection system, in accordance with aspects of the present inventive concepts.
FIG. 11G2 is a conceptual diagram of an embodiment of a rotor system configured to perform Schlieren imaging, in accordance with aspects of the present inventive concepts.
FIG. 11H1 is a perspective view of an embodiment of a rotor system comprising a hyperspectral image detection system, in accordance with aspects of the present inventive concepts.
FIG. 11H2 is a conceptual diagram of an embodiment of a rotor system configured to perform hyperspectral imaging, in accordance with aspects of the present inventive concepts.
FIG. 12B1 is a perspective view of an embodiment of a subunit comprising at least one sample region and a temperature control system, in accordance with aspects of the present inventive concepts.
FIG. 12B2 is a close-up perspective view of an embodiment of a sample region from FIG. 12B1, in accordance with aspects of the present inventive concepts.
FIG. 12B3 is a top view of an embodiment of a sample subunit comprising a thermal channel, in accordance with aspects of the present inventive concepts.
FIG. 12B4 is a close-up perspective view of an embodiment of a temperature control element and a stirrer, in accordance with aspects of the present inventive concepts.
Reference will now be made in detail to the present embodiments of the technology, examples of which are illustrated in the accompanying drawings. Similar reference numbers may be used to refer to similar components. However, the description is not intended to limit the present disclosure to particular embodiments, and it should be construed as including various modifications, equivalents, and/or alternatives of the embodiments described herein.
It will be understood that the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) when used herein, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof
It will be further understood that, although the terms first, second, third etc. may be used herein to describe various limitations, elements, components, regions, layers and/or sections, these limitations, elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one limitation, element, component, region, layer or section from another limitation, element, component, region, layer or section. Thus, a first limitation, element, component, region, layer or section discussed below could be termed a second limitation, element, component, region, layer or section without departing from the teachings of the present application.
It will be further understood that when an element is referred to as being “on”, “attached”, “connected” or “coupled” to another element, it can be directly on or above, or connected or coupled to, the other element, or one or more intervening elements can be present. In contrast, when an element is referred to as being “directly on”, “directly attached”, “directly connected” or “directly coupled” to another element, there are no intervening elements present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g. “between” versus “directly between,” “adjacent” versus “directly adjacent,” etc.).
It will be further understood that when a first element is referred to as being “in”, “on” and/or “within” a second element, the first element can be positioned: within an internal space of the second element, within a portion of the second element (e.g. within a wall of the second element); positioned on an external and/or internal surface of the second element; and combinations of one or more of these.
As used herein, the term “proximate” shall include locations relatively close to, on, in and/or within a referenced component, anatomical location, or other location.
Spatially relative terms, such as “beneath,” “below,” “lower,” “above,” “upper” and the like may be used to describe an element and/or feature's relationship to another element(s) and/or feature(s) as, for example, illustrated in the figures. It will be further understood that the spatially relative terms are intended to encompass different orientations of the device in use and/or operation in addition to the orientation depicted in the figures. For example, if the device in a figure is turned over, elements described as “below” and/or “beneath” other elements or features would then be oriented “above” the other elements or features. The device can be otherwise oriented (e.g. rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
The terms “reduce”, “reducing”, “reduction” and the like, where used herein, are to include a reduction in a quantity, including a reduction to zero. Reducing the likelihood of an occurrence shall include prevention of the occurrence.
The term “and/or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example, “A and/or B” is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein.
In this specification, unless explicitly stated otherwise, “and” can mean “or,” and “or” can mean “and.” For example, if a feature is described as having A, B, or C, the feature can have A, B, and C, or any combination of A, B, and C. Similarly, if a feature is described as having A, B, and C, the feature can have only one or two of A, B, or C.
The expression “configured (or set) to” used in the present disclosure may be used interchangeably with, for example, the expressions “suitable for”, “having the capacity to”, “designed to”, “adapted to”, “made to” and “capable of” according to a situation. The expression “configured (or set) to” does not mean only “specifically designed to” in hardware. Alternatively, in some situations, the expression “a device configured to” may mean that the device “can” operate together with another device or component.
It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. For example, it will be appreciated that all features set out in any of the claims (whether independent or dependent) can be combined in any given way.
It is to be understood that at least some of the figures and descriptions of the disclosure have been simplified to focus on elements that are relevant for a clear understanding of the disclosure, while eliminating, for purposes of clarity, other elements that those of ordinary skill in the art will appreciate may also comprise a portion of the disclosure. However, because such elements are well known in the art, and because they do not necessarily facilitate a better understanding of the disclosure, a description of such elements is not provided herein.
Terms defined in the present disclosure are only used for describing specific embodiments of the present disclosure and are not intended to limit the scope of the present disclosure. Terms provided in singular forms are intended to include plural forms as well, unless the context clearly indicates otherwise. All of the terms used herein, including technical or scientific terms, have the same meanings as those generally understood by an ordinary person skilled in the related art, unless otherwise defined herein. Terms defined in a generally used dictionary should be interpreted as having meanings that are the same as or similar to the contextual meanings of the relevant technology and should not be interpreted as having ideal or exaggerated meanings, unless expressly so defined herein. In some cases, terms defined in the present disclosure should not be interpreted to exclude the embodiments of the present disclosure.
An integrated rotor device for autonomous analytical centrifugation offers advantages over former approaches in that the rotating device itself is equipped with all the means to complete an AUC assay, with the exception of the centrifugal force, in contrast to the previous art where the majority of the measurement functions are carried out on modules located within the centrifuge, rather than by assembling the critical components within the confines of a rotor. Therefore, by locating most of the assay functionality into self-contained modules or cells within a spinning rotor apparatus, the embodied device is versatile and efficient, and can be used with a range of centrifuges including smaller, cost effective bench-top (table-top) centrifuges where lower centrifugal speeds are sufficient, such as in the analysis of high molecular weight biological species including viral particles and gene delivery vectors. Furthermore, by having the light source, sample, and detector all move together (in register) during sedimentation, in the rotating frame of reference, the speed of data acquisition, and the quality of data, are improved, resulting in higher resolution and precision in the numerical results.
In this manner, a system is provided that is portable, cost-effective, and versatile in its measurement capabilities, and that allows for the collection of high quality sedimentation profile data.
In an embodiment of the device, cells can be loaded into the rotor without the need for any special cell alignment, as such cell alignment can be highly subjective, based on interpretation by the user operating the equipment.
In another embodiment, numerical output of the sedimentation data can be provided in a retrievable digital format, following a minimum of input parameters required of the technician operating the device.
In another embodiment, numerical output of the sedimentation data can be provided in a retrievable digital format, in real-time during the sedimentation, by means such as Wi-Fi, Bluetooth, or other wireless mode for transmission of the data to an external unit or to Cloud Storage.
In another embodiment, robust temperature control of the fluid chamber can be provided by thermostatic devices (such as thermoelectric units) placed internally in the rotor device and nearby the fluid-chamber region of the device.
In another embodiment, high speed data acquisition, and improved data quality, can be provided by collecting light absorbance, interference, or fluorescence profiles across the radial dimension of each fluid chamber simultaneously along said radial dimension, via the use of a diode array, rather than sequentially, via the use of a detector on a radially moving armature system.
In another embodiment, an improvement in the quality of AUC data can be provided by collecting light absorbance, interference, or fluorescence profiles across the radial dimension of the fluid chamber while the source and detector remain fixed in the same frame of reference as the fluid chamber (the rotating frame of reference), during centrifugation and data collection.
A measurement device is in the form of an assembly of integrated modules and/or functional cells, within a rotor, and contains—internal to the rotor—all provisions for the acquisition of sedimentation profile data in the manner of a controlled AUC assay.
In some embodiments, a fluid chamber region confines the sample and/or reference fluids in a sector-shaped geometry. The fluid chamber is a walled unit, or multiple such units, that are open on the top and bottom faces and are bounded on the top and bottom faces by transparent windows that may be affixed to each open face of the chamber, sealing the unit in all directions against leakage, and allowing the passage of electromagnetic radiation, such as visible or UV light, and other types of sample monitoring.
An assembly of integrated modules or functional cells within a rotor body, is configured with the rotor body having an opening or cavity that is coincident with the axis of rotation so that the rotor may be placed atop the drive shaft (spindle) of a centrifuge, in a manner similar to conventional analytical rotors (i.e. non-functional or non-data acquiring rotors which are simply structural units composed of e.g. solid titanium). The cavity is configured to accept the drive shaft and with proper adaptation may be acceptable to a plurality of shaft dimensions.
A centrifuge, which is external to, and separate from the rotor device, and in which the rotor device is placed, provides centrifugal force which causes sedimentation in the sample and/or reference chambers. In some embodiments, a source of electromagnetic radiation (light source) and a detector are affixed along a linear axis that is parallel to the axis of rotation and coincident with a straight line that traverses the transparent windows that bound the top and bottom faces of the fluid chamber.
In some embodiments, a separate light source and detector are placed along the linear axis through each separate fluid chamber that is housed within a cell structure and/or within the entire rotor device. In some embodiments, the light source and detector are rigidly affixed within the rotor device, so as to maintain the co-linear positioning of the light source, fluid chamber, and detector at all times before, during, and after centrifugation; in this manner each fluid chamber may be illuminated, and sedimentation subsequently detected, simultaneously across the radial dimension of each sample/reference chamber, and likewise each separate fluid chamber may also be illuminated and detected simultaneously with (and/or independently of) any other chamber.
In some embodiments, the light source, detector, and other modules stacked together in a rigid sleeve or housing, which may be considered a functional cell, which can be removed from the rotor, and then rigidly affixed to back to the rotor at appropriate times prior to the start of an assay.
The source of radiation associated with each chamber may be a single diode or an array of light emitting diodes that uniformly illuminate the radial dimension of each chamber, and the detector can likewise be a corresponding array of diodes, charge coupled devices, or the like, which develop a voltage or current as a function of illumination. The respective voltages or amperages can be shifted to a threshold detector means for encoding light intensity levels at the pixels and comparing the intensity levels for resolving the sedimentation profiles in each chamber at prescribed times throughout the sedimentation. The radiation and detection functions are managed and controlled by a microprocessor and appropriate circuitry and chipsets, to likewise control and maintain the desired chamber temperature, process the samples accurately in a programmed manner, and calculate and display the results numerically.
The depiction of
The depiction of
Also surrounding each sample chamber 6 are thermostat units 9 which may be thermoelectric circuit components, and may be located in close proximity to the sample chamber 6 for the purpose of maintaining a constant temperature in the region where the sample fluid resides, and in particular in the fluid itself, to buffet against any temperature gradients which may arise from irradiation of the fluid or nearby circuitry, or other sources. Although not detailed in
Finally in
Furthermore, the cell units 14 embodied in
A key-way 18 extends along the cavity wall in a direction parallel to the axis of rotation. The key-way 18 is constructed and arranged to mate with components that are stacked inside the optical cavity, to provide precise and robust alignment of the components with respect to the axis of rotation. Each key-way 18 inside each cavity may be removable or may be a rigid, continuous part of the cavity wall, as may be desired for precise and robust alignment and positioning of the stacked components. From the top view, the key-way 18 appears as a ridge protruding into the optical cavity, and extends the length of the cavity from top to bottom.
One or more thermostat devices 19, such as thermoelectric modules, may be positioned around the optical cavity. The one or more thermo-electric devices 19 may be rectangular in shape having some fixed thickness. In some embodiments, the thermo-electric devices 19 may be curved, so as to surround the optical cavity to better maintain the temperature in the vicinity of one or more sample/reference chambers. In the embodiment shown in
In some embodiments, the integrated rotor device contains a card-slot 20. The card-slot 20 may be constructed and arranged to couple with an electric circuit board. In some embodiments, the circuit board is coupled to the one or more thermo-electric devices 19 by any suitable means, such as ribbon-cable or cable-cord connectors. Measurement components (including, but not limited, to the light sources and detectors) may also be coupled to the circuit board. The circuit board may comprise a central microprocessor unit (CPU). The circuit board may further comprise other chip sets and circuit components, including, but not limited to, digital memory modules, rechargeable batteries for supplying power, and overall management of the measurement and temperature control in a programmable manner. Although
The integrated rotor device may comprise a centerpiece 21. In some embodiments, the centerpiece 21 is a walled unit that encloses sector-shaped compartments of the sample and/or reference solutions (fluids).
Specifically, a sector-shaped geometry is defined as the volume element of a cylindrical segment having the cross-sectional area of a circular sector (an area enclosed by two radii of a large circle, an arc of the larger circle, and an arc of a smaller concentric circle of lesser radius).
In some embodiments, the centerpiece 21 is inserted from the bottom of the rotor, up through the cavity walls, and the centerpiece is pushed upwards until it meets with the collar 17. In some embodiments, the centerpiece comprises a first ridge on an upper surface that couples with the collar and allows the upper surface of the centerpiece 21 to protrude slightly above the collar 17. The centerpiece 21 may include a second ridge that allows it to couple with the key-way 18, for precise alignment of the centerpiece 21 in the optical cavity.
In some embodiments, a bottom window unit 22 is inserted from the bottom of the optical cavity. In some embodiments, the bottom window unit 22 is a rigid metal housing into which a transparent (quartz or the like) cylindrical window is held. The bottom window unit 22 may also have a key-way mating ridge as part of its structure, for precise and optimal alignment of the window. In the embodiment shown in
In some embodiments, a detector unit 23 is inserted from the bottom of the optical cavity and pushed upwards in a similar manner. The detector unit 23 can also contain a key-way mating ridge as part of its structure, for the same purposes as described above for the centerpiece, etc. The detector 23 may be of a certain geometry such that part of the detector device may protrude upwards and allow it to mate with an opening in the bottom window holder 22 structure, allowing for close contact between parts of the detector and the (e.g. quartz) window surface.
In some embodiments, the detector unit 23 is constructed and arranged to resolve the differential absorbance (or other signal) that is spread out over the radial dimension in the sample chamber, as sedimentation occurs during centrifugation. In some embodiments, the detection is accomplished by a linear arrangement of an array of detector units, such as an array of diodes that can detect the intensity of light, or other detection means such as fluorescence, refraction, etc. Because the detector 23 is affixed in register with the sample chamber, the detector 23 is designed to experience the same centrifugal velocity as the sample chamber. In some embodiments, the detector 23 can be programmed to acquire data at any desirable time during centrifugation, simultaneously across the radial dimension and independently of any other sample chamber being centrifuged in the same rotor. In some embodiments, the detector 23 is designed to transmit it signals, such as voltages or current values, by means of a wire connect to the card-slot peripheral 20 (refer to
In some embodiments, a bottom gasket 24 is pushed up from the bottom of the optical cavity to interface with the bottom face of the detector unit 23. In some embodiments, a bottom screw ring 25 is also affixed from the bottom, which mates with threads in the wall of the optical cavity. The purpose of the bottom screw ring 25 is to provide a significant tension force that can be adjusted and made to press together all the subunits of the bottom half of the cavity, which press against the collar 17. Once sufficient tension force is applied via the bottom screw ring 25, the bottom half of the subunits provide a leak-tight junction between the inner walls of the centerpiece 21 (the sample/reference chambers) and the bottom face of the centerpiece which meets flush with the window surface.
In some embodiments, the sample and/or reference fluids may be pipetted into the open face of the fluid-tight chambers from above, i.e. the sector shaped chambers of the centerpiece 21. Note that by first sealing the centerpiece and the bottom window by providing tension against the collar, the sector-shaped chamber is fluid-tight and can be filled with a certain volume of fluid via top of the chamber which remains open until the top window is applied.
In some embodiments, after inserting the fluids, a top window assembly 26 is placed down over the centerpiece 21. In some embodiments, the top window assembly 26 is aligned with the key-way 18 (
In some embodiments, a light source 27 is inserted down into the cavity. In some embodiments, the light source 27 comprises a key-way ridge for alignment. In some embodiments, the light source 27 is constructed and arranged to provide uniform sample illumination. The light source 27 may be a monochromatic or narrow band wavelength or may be a broadband source that is made monochromatic by sufficient means for transmission through the light source module.
Similar to the bottom half of the cavity assembly, the top portion may be sealed by means of a top gasket 28 and a top screw ring 29. Once the top screw ring 29 is fully torqued down, the entire stack is a fluid-tight and air-tight stack enclosed in the rotor body. Because there are electrical connections between the light source-CPU and detector-CPU, the illumination and subsequent detection across the sample chamber can be operated in a controlled and programmed manner. The input of experimental parameters is intended to be entered by the operator prior to the placement of the device in the centrifuge, by means of a separate electrical connection between the device and a workstation, such as by USB connection.
In some embodiments, the rotor body 1 comprises one or more stacked subunits 30. In the embodiment shown in
In the embodiment shown in
In the embodiment shown in
In the embodiment shown in
In some embodiments, one or more of the one or more subunits 30 comprise an opening 31 constructed and arranged to allow for the insertion of a central projection (not shown in
In some embodiments, the base subunit 32 comprises a central projection 34. The central projection 34 extends in a vertical direction transverse to a horizontal direction of extension x of the base subunit 32. In some embodiments, the central projection 34 comprises a material of high strength and is configured to absorb and distribute the centrifugal force of the centrifuge's drive shaft. In some embodiments, the central projection 34 comprises a transmitter 200, the transmitter 200 being constructed and arranged to transmit information from the rotor system 100 to an external location. In some embodiments, the transmitter 200 comprises a broadcast antenna. In some embodiments, the transmitter 200 transmits a wireless electromagnetic signal.
In
In some embodiments, one or more of the one or more subunits 30 comprise one or more sample regions 40. The embodiment shown in
In some embodiments, one or more of the one or more subunits 30 comprise one or more window regions 45. In
In some embodiments, one or more of the one or more sample regions 40 comprises a sector shape. Specifically, a sector-shaped geometry is defined as the volume element of a cylindrical segment having the cross-sectional area of a circular sector (an area enclosed by two radii of a large circle, the bounding arc of the larger circle between the radii, and an arc of a smaller concentric circle of lesser radius). In addition, a sector-shaped geometry comprises at least two boundaries that coincide with radial lines that emanate outward from the axis of rotation, the radial direction being defined as the direction that extends radially outward from the axis of rotation 103.
In some embodiments, the rotor system 100 comprises one or more functional components. The embodiment shown in
FIG. 8G1 is a close-up perspective view of an embodiment of a functional element 149 and the associated connector 151, in accordance with embodiments of the present inventive concepts. In the embodiment shown in FIG. 8G1, the functional element 149 comprises a circuit board. In the embodiment shown in FIG. 8G1 the connector 151 comprises a ribbon cable. In alternative embodiments, the connector 151 comprises connections including, but not limited to USB connections, micro-USB connection, VGA connections, D-type connections, or other mechanisms suitable for transferring power and/or information.
In alternative embodiments, alternative geometries can be employed such that electromagnetic radiation can be guided in and out the sample region by various optics, for example light pipes, mirrors, fiber optics, focusing lenses, or other suitable optical devices.
In the embodiment shown in
FIG. 8H1-8H5 illustrate a method of assembling a rotor system 100, in accordance with embodiments of the present inventive concepts. In some embodiments, the rotor system 100 is assembled from the bottom up. For example, for assembling some embodiments, one subunit 30j comprising a sample region 40 is positioned above a second subunit 30i, as shown in FIG. 8H1. In this embodiment, the sample region 40 comprises sector-shaped side walls, and is open at the top and bottom.
FIG. 8H2 is a perspective view of an embodiment of the two subunits 30i-j of FIG. 8H1 coupled with an air-tight and liquid-tight junction, in accordance with aspects of the present inventive concepts. In this embodiment, a surface in the lower subunit 30i serves as a lower surface for the sample region 40.
FIG. 8H3 is a perspective view of an embodiment of a sample being added to the sample region 40, in accordance with aspects of the present inventive concepts.
FIG. 8H4 is a perspective view of an embodiment of an additional subunit 30k being added above the sample region 40, in accordance with aspect of the present inventive concepts. In this embodiment, the top subunit 30k is coupled to another subunit 30j with an air-tight, liquid-tight seal. A surface in the top subunit 30k serves as an upper surface of the sample region 40.
FIG. 8H5 is a perspective view of an embodiment of the three subunits coupled together, in accordance with aspects of the present inventive concepts.
Alternative embodiments comprise a different number of subunits. For example, in assembling an embodiment such as the one illustrated in
In some embodiments, the first window subunit 30b is positioned above the sample subunit 30c. In some embodiments, a sample is inserted into the sample region 40 before the first window subunit 30b is positioned above the sample subunit 30c. In such cases, the first window 110a is positioned directly above the sample region 40 and the first window 110a serves as a boundary for the sample region 40. In some embodiments, the source subunit 30a is positioned above the first window subunit 30b.
In some embodiments, the first window subunit 30b is positioned above the sample subunit 30c. In some embodiments, a sample is inserted into the sample region 40 before the first window subunit 30b is positioned above the sample subunit 30c. In such cases, the first window 110a is positioned directly above the sample region 40 and the first window 110a serves as a boundary for the sample region 40. In some embodiments, the source subunit 30a is positioned above the first window subunit 30b.
In some embodiments the sample region 40 comprises a sample chamber 106 that is constructed and arranged to be positioned in the sample region 40. In such embodiments, the sample chamber 106 comprises a top window that is transparent to one or more wavelengths in the electromagnetic spectrum. In some embodiments, the sample chamber 106 comprises a bottom window that is transparent to one or more wavelengths in the electromagnetic spectrum. In some embodiments, the top window of the sample chamber 106 is transparent to one or more wavelengths emitted by the source of electromagnetic radiation 107. In some embodiments, the bottom window is transparent to one or more wavelengths emitted from the sample region 40. In some embodiments, the sample chamber 106 comprises a key-way 118 such that it is coupled to the sample subunit. The key-way 118 can be constructed and arranged to hold the sample chamber 106 in position.
In some embodiments the sample chamber 106 is constructed and arranged to be removable from the sample region 40. In the embodiment shown in
In the embodiment of
In some embodiments, the windows 110a, 110b at each window region 45a, 45b and the windows at the sample chamber 106 may all pass substantially similar wavelengths of electromagnetic radiation. In such cases, the source of electromagnetic radiation 107 may be aligned with the first detector 108a. The electromagnetic radiation may pass through the window 110a at the first window layer 45a, pass through the window at the sample chamber 106, and interact with the sample. The scattered electromagnetic radiation may then pass through the lower window in the sample chamber 106, the window 110b at the second window layer 45b, and then reach the detector 108a.
In some embodiments, different windows transmit different wavelengths of electromagnetic radiation. For example, the electromagnetic radiation emitted from the source of electromagnetic radiation 107 may need to be filtered before propagating to the sample region 40. In such cases, the first window 110a at the first window layer 45a and/or the top window at the sample chamber 106 may perform such filtering.
In some embodiments, the wavelengths of electromagnetic radiation to be detected may not match the wavelengths of electromagnetic radiation emitted from the source of electromagnetic radiation 107 (e.g. fluorescence imaging, Raman imaging, etc.). In such cases, the window 110b at the second window layer 45b and/or the bottom window at the sample chamber 106 may perform the necessary filtering.
In the embodiment shown in
In some embodiments, the rotor system 100 comprises other components, such as additional integrated circuits, memory units, transmitter/receivers, and sensors. Such components may likewise be located on the various subunits 30 and may be positioned with respect to the axis of rotation 103 so as to provide a symmetric weight distribution for the resulting rotor.
In the embodiment shown in
FIG. 11D1 and FIG. 11D2 are perspective views of an embodiment of sources of electromagnetic radiation, in accordance with aspects of the present inventive concepts. In some embodiments, a source of electromagnetic radiation 107 is positioned above each sample region 40. In some embodiments, the source of electromagnetic radiation 107 comprises one or more light-emitting diodes. In alternative embodiments, there may be one or more sources of electromagnetic radiation 107 that direct incident electromagnetic radiation 50 to the sample region 40 via fiber optics, mirrors, waveguides, or other mechanisms suitable for conveying electromagnetic energy.
FIG. 11G1 is a perspective view of an embodiment of a rotor system 100 comprising a Schlieren image detection system, in accordance with aspects of the present inventive concepts. In this embodiment, the source subunit 30 comprises a window 76, and the detection subunit comprises a window 86. Electromagnetic radiation passes through the window 76 in the source subunit and into the sample region 40. The electromagnetic radiation from the sample region 40 passes through the window 86 on the detection subunit and passes through a focusing lens 92. The electromagnetic radiation is focused though an iris 94. The iris 94 can be positioned at the focal position of the focusing lens 92. In this embodiment, a Schlieren image is formed at the detector 108. In alternative embodiments, the iris 94 is replaced with a knife-edge or any suitable edge geometry capable of blocking a portion of the electromagnetic radiation.
FIG. 11G2 is a conceptual diagram of an embodiment of a rotor system 100 configured to perform Schlieren imaging, in accordance with aspects of the present inventive concepts. This embodiment is similar to the embodiment of FIG. 11G1. In this embodiment, temperature control elements 109 are positioned near the sample region 40. In this embodiment, the source of electromagnetic radiation 107, the detector 108, and the temperature control elements 109 are coupled to a CPU 10A, memory 10B, a battery 10C, a wireless transmitter 10D, and/or additional circuitry.
FIG. 11H1 is a perspective view of an embodiment of a rotor system 100 comprising a hyperspectral image detection system, in accordance with aspects of the present inventive concepts. In this embodiment, the source subunit comprises a window 76 and the detection subunit comprises a window 86. Electromagnetic radiation passes through the window 76 at the source subunit and into the sample region 40. The electromagnetic radiation from the sample region 40 passes through the window 86 at the detection subunit and passes through a lens system 82. The electromagnetic radiation then passes through a Fabry-Perot interferometer 96 before reaching the detector 108.
FIG. 11H2 is a conceptual diagram of an embodiment of a rotor system 100 configured to perform hyperspectral imaging, in accordance with aspects of the present inventive concepts. This embodiment is similar to the embodiment of FIG. 11H1. In this embodiment, temperature control elements 109 are positioned near the sample region 40. In this embodiment, the source of electromagnetic radiation 107, the detector 108, and the temperature control elements 109 are coupled to a CPU 10A, memory 10B, a battery 10C, a wireless transmitter 10D, and/or additional circuitry.
FIG. 12B1 is a perspective view of an embodiment of a subunit 30 comprising at least one sample region 40 and a temperature control system 700, in accordance with aspects of the present inventive concepts. In some embodiments, the temperature control system 700 comprises one or more temperature control elements 109, such as, but not limited to, a Peltier unit (FIG. 12B4). In some embodiments, one or more temperature control elements 109 neighbor one or more of the sample regions 40 in the rotor system 100. In some embodiments, there are fewer temperature control elements 109 than sample regions 40.
In some embodiments, the temperature control system 700 comprises an active pumping mechanism and one or more thermal channels 720. In some embodiments, the active pumping mechanism pumps a thermally conductive fluid 730 through the one or more thermal channels 720. The temperature control elements 109 heat or cool the thermally conductive fluid 730 and the fluid is pumped through the thermal channels 720. The thermal channels 720 are positioned near one or more sample regions 40 and the presence of the thermally conductive fluid 730 modifies the temperature in the sample region 40.
In some embodiments, the temperature control system 700 comprises one or more stirrers 710. In some embodiments, the one or more stirrers 710 help to move the thermally conductive fluid 730 through the thermal channels 720.
FIG. 12B2 is a close-up perspective view of an embodiment of a sample region 40 from FIG. 12B1, in accordance with aspects of the present inventive concepts. In the embodiments shown in FIG. 12B2, the temperature control system 700 comprises a temperature sensor 740 that is coupled to the sample region 40. The temperature sensor 740 measures the temperature at the sample region 40 and transmits that information to the temperature control system 700, via a wired or wireless connection. In some embodiments, the temperature control system 700 compares the measured temperature to a predetermined set point. In some embodiments, if the measured temperature deviates from the predetermined set point, the temperature control system 700 takes steps to reduce this difference. In some embodiments, the temperature control system 700 reduces the temperature difference by adjusting one or more temperature control elements 109 or by adjusting the flow of the thermally conductive fluid 730. In some embodiments, the temperature sensor 740 comprises an alarm that indicates when the temperature deviates by a certain amount from a predetermined set point. In the embodiment shown in FIG. 12B2, a thermal channel 720 neighbors the sample region 40 and is oriented along the axis of rotation 103.
FIG. 12B3 is a top view of an embodiment of a sample subunit 30 comprising a thermal channel 720, in accordance with aspects of the present inventive concepts. In this embodiment, the sample subunit 30 comprises four sample regions 40, symmetrically aligned about the rotor's axis of rotation 103. The thermal channel 720 extends symmetrically though the sample subunit (only the upper left quadrant is displayed). In this embodiment, the thermal channel 720 is oriented transverse to the axis of rotation 103.
FIG. 12B4 is a close-up perspective view of an embodiment of a temperature control element 109 and a stirrer 710, in accordance with aspects of the present inventive concepts.
In addition to being connected via the electrolyte solution 830, a separate electrical wiring connection 840 is maintained between the two terminals 810, 820. In the figure, current is driven through the wiring, as shown, by an induced ion concentration gradient which occurs due to the centrifugal force exerted on the system. In some embodiments, unlike the conventional concentration-type voltaic cell, the local ionic concentration at the vicinity of each electrode is prevented from being equalized as long as sufficient centrifugal force is applied, and therefore will run under centrifugation as long as solid electrode material is available at each terminal. In some embodiments, a multitude of cells of the type shown here may be interconnected in series and/or in parallel, to form a battery-like configuration which may supply power on board the rotating device.
In some embodiments, each cell 850 comprises a topmost layer which comprises a material that emits beta particles by radio-isotopic decay 860. In some embodiments, immediately below the beta emitting layer 860 is a layer comprising n-type semiconductor material 870, which releases electrons, as donors, upon irradiation with high energy beta particles. In some embodiments, immediately below the n-type material is a layer comprising p-type semiconductor material 880, forming a p-n semiconductor junction. In some embodiments, the layer comprising p-type semiconductor material 880 is positioned above a base 890.
Irradiation of the n-type layer 870 above the p-n junction drives a current through terminals 875, 885 attached at the junctions above and below the p-n junction, as shown, which may drive electrical work when connected to a load.
It is noted that the mounting systems described herein at least in connection with
It is noted that the subunit systems described herein at least in connection with
It is noted that the window systems described herein at least in connection with
It is noted that the battery systems described herein at least in connection with
It is noted that the optical systems described herein at least in connection with
It is noted that the temperature control systems described herein at least in connection with
Directly below the sample subunit 530c is a second window subunit 530d. The second window subunit 530b comprises a second window region 545b. The second window region 545b comprises at least one window 510b positioned below the sample region 540. In this embodiment, each window subunit 530b, d comprises a transparent window 510a, b that allows for the transmittance of electromagnetic radiation through the sample region 540. The subunits 530 may comprise other functional components, which may be components of integrated circuits on printed circuit boards, including, but not limited to, a source subunit 530a and a detection subunit 530e. In the embodiment shown in
In some embodiments, the source subunit 530a comprises a source of electromagnetic radiation 524. Examples of the source of electromagnetic radiation 524 include, but are not limited to, a light-emitting diode, a laser diode, gas-discharge arc-lamps (e.g. deuterium arc lamp or a xenon arc lamp), and an incandescent source. In some embodiments, the detection layer 530e comprises a detector 525. In some embodiments, the detector 525 is coupled to a circuit. In some embodiments, the detector comprises a detector array.
In the embodiment of
In some embodiments, the windows 510a,b in each window region 545a, 545b and the windows on the sample chamber 506 may all pass substantially similar wavelengths of electromagnetic radiation. In such cases, the source of electromagnetic radiation 524 may be aligned with the first detector 525. The electromagnetic radiation may pass through the window 510a at the first window layer 545a, pass through the window at the sample chamber 506, and interact with the sample. The scattered electromagnetic radiation then passes through the lower window in the sample chamber 506, the window 510b at the second window layer 545b, and then reaches the detector 525.
In some embodiments, different windows transmit different wavelengths of electromagnetic radiation. For example, the electromagnetic radiation emitted from the source of electromagnetic radiation 524 may need to be filtered before propagating to the sample region 540. In such cases, the window 510a at the first window layer 545a and/or the top window at the sample chamber 506 may perform such filtering.
In some embodiments, the wavelengths of electromagnetic radiation to be detected may not match the wavelengths of electromagnetic radiation emitted from the source of electromagnetic radiation 524 (e.g. fluorescence imaging, Raman imaging, etc.). In such cases, the window 510b at the second window layer 545b and/or the bottom window at the sample chamber 506 may perform the necessary filtering.
In the embodiment shown in
In alternative embodiments, other components, such as additional integrated circuits, memory units, transmitter/receivers, and sensors may likewise be located on one or more layers. In some embodiments, additional components are symmetrically positioned with respect to the axis of rotation.
In the embodiment shown in
In alternative embodiments, the source of electromagnetic radiation 524 emits electromagnetic radiation with a different divergence. In alternative embodiments, the cell 500 comprises at least one collimator that collimates the beam of electromagnetic radiation 26 as it traverses the sample region 540. In some embodiments, the electromagnetic radiation 26 is directed over the entire sample region 540. In alternative embodiments, the electromagnetic radiation 26 is directed over the entire sample region 540 and is collimated as it is directed over the entire sample region 540.
Although the electromagnetic radiation 26, illustrated in
The above-described embodiments should be understood to serve only as illustrative examples; further embodiments are envisaged. Any feature described herein in relation to any one embodiment may be used alone, or in combination with other features described, and may also be used in combination with one or more features of any other of the embodiments, or any combination of any other of the embodiments. Furthermore, equivalents and modifications not described above may also be employed without departing from the scope of the specification, which is defined in the accompanying claims.
This application claims the benefit of U.S. Provisional Application No. 62/635,514 filed on Feb. 26, 2018, the content of which is incorporated herein by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US19/19691 | 2/26/2019 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62635514 | Feb 2018 | US |
