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US-20260126459-A1 - MODULE FOR DETECTING OR MEASURING ANALYTES IN FLUID

US20260126459A1US 20260126459 A1US20260126459 A1US 20260126459A1US-20260126459-A1

Abstract

Aspects of the present disclosure describe an analytical module for performing automated assays on fluids. The present disclosure provides an analytical module comprising a cylindrical housing attached to a rigid base supporting a motor. The housing includes magnets and a sensor. The module comprises a shuttle attached to the rotating motor shaft, nested within and free to rotate in the housing, configured to hold reaction vessels, and comprising a flag that interacts with the sensor to define position. The module includes a detector connected to the housing and a shroud shielding the detector from ambient light. The disclosure provides an immunoassay module with a system to perform magnetic bead-based immunoassays configured to shake reaction vessels for mixing and bead resuspension. Methods for performing immunoassays using the analytical module are provided.

Inventors

  • Robert GRANIER
  • Anthony Lawrence Maida
  • Jesse Newton Jones, IV
  • Daniel Morris HARTMANN

Assignees

  • GENERAL FLUIDICS CORPORATION

Dates

Publication Date
20260507
Application Date
20251107

Claims (20)

  1. 1 . An analytical module comprising: a rigid base; a motor rigidly attached to the rigid base; a cylindrical housing rigidly attached to the rigid base and having a hole in a bottom through which a shaft of the motor protrudes, the housing including one or more magnets and a sensor; a shuttle attached to a rotating shaft of the motor, the shuttle being nested within the housing and free to rotate within the housing, the shuttle configured to hold one or more reaction vessels, and comprising a flag configured to interact with the sensor on the housing to define a unique position; a detector connected to the housing; and a shroud positioned so as to shield the detector from ambient light.
  2. 2 . The analytical module of claim 1 wherein the motor may be driven back-and-forth to cause the shuttle containing the one or more reaction vessels to rotate back-and-forth and thereby cause a liquid within the reaction vessels to mix, and to cause particles within the reaction vessels to be resuspended.
  3. 3 . The analytical module of claim 2 wherein the motor is driven back-and-forth at a frequency of between 1 and 20 cycles per second.
  4. 4 . The analytical module of claim 2 wherein the motor that causes the shuttle to oscillate back and forth for mixing may also be used to position the shuttle at precise locations in the housing.
  5. 5 . The analytical module of claim 1 wherein the analytical module further includes a double pipettor probe configured to interact with the one or more reaction vessels, the double pipettor probe including a first probe and a second probe.
  6. 6 . The analytical module of claim 1 wherein the analytical module further includes a wash manifold configured to translate up and down between two positions, the wash manifold having pairs of aspirate and dispense probes, each pair of probes being configured so that when the wash manifold is in one of its position, the probes are engaged with corresponding reaction vessels.
  7. 7 . The analytical module of claim 6 wherein the shuttle can be rotated between multiple unique positions in the housing, the positions including; (a) a reaction vessel load and reaction vessel unload position where one or more reaction vessels may be loaded and unloaded; (b) a magnet-engagement position where the one or more reaction vessels abut magnets in the housing; (c) a wash position in which the one or more reaction vessels are positioned under the wash manifold and may engage with the wash manifold when it is one of its positions; (d) a shake position in which the one or more reaction vessels are positioned far enough away from the magnets that a force from the magnets has no appreciable effect on contents of the one or more reaction vessels, and the one or more reaction vessels may be aggressively shaken back-and-forth to mix their contents and/or resuspend one or more particles within them; and (e) a read position in which the one or more reaction vessels may be sequentially positioned next to the detector so that light from within or shining through the one or more reaction vessels may be collected by the detector.
  8. 8 . The analytical module of claim 1 , wherein the rotating shuttle is also a heatblock and has an attached heating element.
  9. 9 . The analytical module of claim 1 , wherein each reaction vessel has a drain, and the rotating shuttle further includes a valve configured to gate the drain of each reaction vessel.
  10. 10 . The analytical module of claim 9 , wherein the module further includes a manifold including one or more fluidic paths fluidically connected to the one or more reaction vessels through the valves.
  11. 11 . An immunoassay module including: a system to perform magnetic bead based immunoassays wherein the system is configured to shake one or more reaction vessels back and forth to accomplish mixing and bead resuspension.
  12. 12 . The immunoassay module of claim 11 , wherein the module includes: a rigid base; a motor connected to the rigid base; a linear translation stage configured to translate along the base; a shuttle connected to the linear translation stage so that the shuttle moves linearly with the linear translation stage; one or more reaction vessels connected to the translating shuttle; a detector connected to the base, the detector being at least partially covered by an opaque shroud; a magnet-manifold connected to the base, a magnet manifold including one or more magnets; and a sensor connected to the shuttle that works in concert with another piece of hardware mounted to the base, such as a magnet, flag, or piece of metal, to define a particular position along the base.
  13. 13 . The immunoassay module of claim 12 wherein the system further includes a wash manifold configured to translate up and down between two positions, the wash manifold having pairs of aspirate and dispense probes, each pair of probes being configured so that when the wash manifold is in one of its position, the probes are engaged with corresponding reaction vessels.
  14. 14 . The immunoassay module of claim 11 , wherein the module includes: a fluidic sub-assembly having reaction vessels with output drains and valves that gate the outputs of the reaction vessels; and a shaker sub-assembly to which the fluidic sub-assembly may be mounted, the shaker sub-assembly having a shake motor separate and distinct from that of a positioning motor, the shake motor being configured to shake the fluidic sub-assembly back and forth at a frequency between 1 and 50 cycles per second.
  15. 15 . The immunoassay module of claim 14 , wherein the fluidic sub-assembly includes: a heatblock including one or more holes or slots for reaction vessels; one or more reaction vessels having output drains inserted into the slots or holes in the heatblock; a manifold connected to the heatblock, the manifold including one or more O-rings and a waste channel, the O-rings configured to form liquid-tight seals with the outputs of the reaction vessels, and to thereby create passages between the output of the reaction vessels and the manifold; one or more valves connected to the manifold, the valves gating the outputs of the reaction vessels such that when the valves are closed, the reaction vessels cannot drain, but when the valves are open, the outputs of the reaction vessels are connected through the valves to the waste channel; and a pump attached to the waste channel and configured so that when a valve is open, the pump can pull contents of an associated reaction vessel out of the vessel to waste.
  16. 16 . The immunoassay module of claim 14 , wherein the shaker sub-assembly includes: a shaker sub-assembly base; a linear stage shake carriage to connect to an immunoassay fluidic sub-assembly, the linear stage shake carriage connected to the shaker sub-assembly base; a linear stage shake rail connected to the linear stage shake carriage; a scotch yoke connected to the shaker sub-assembly base, the scotch yoke including a scotch yoke pin and scotch yoke follower; and a shake motor connected to the scotch yoke.
  17. 17 . The immunoassay module of claim 14 , the system further including a linear positioning module connected to the shaker sub-assembly.
  18. 18 . The immunoassay module of claim 17 , wherein the linear positioning module includes: a frame; one or more magnets connected to the frame; a wash manifold connected to the frame; a detector connected to the frame; and a linear positioning stage connected to the frame.
  19. 19 . The immunoassay module of claim 11 , wherein the immunoassay module is embedded within a system that further includes: (a) a pipettor mounted to a gantry robot; (b) a reservoir of system fluid; (c) a pump configured to prime system fluid from the reservoir to the pipettor, and aspirate and dispense fluids into the pipettor; (d) a reservoir of cleaning fluid; (e) a waste and wash station for washing the pipettor; (f) a waste pump for pulling fluid out of the waste and wash station; (g) a light cover.
  20. 20 . A method of performing one or more immunoassays with a combination of near-simultaneous actions performed by an instrument assembly based on one or more immunoassay protocols using the analytical module of claim 1 .

Description

CROSS-REFERENCE TO RELATED APPLICATION(S) This patent application claims the benefit of priority to U.S. Provisional Application No. 63/717,779, filed on Nov. 7, 2024, the entirety of which is incorporated herein by reference. TECHNICAL FIELD Various embodiments of the present disclosure relate generally to systems and methods for measuring analytes in fluid, and, more particularly, to systems and methods for an analyzer for measuring analytes in fluid. BACKGROUND Bead-based chemiluminescent immunoassays are among the most sensitive means of detecting proteins in analytical samples, and constitute the gold-standard of clinical diagnostic immunoassays. However, some commercialized immunoassay analyzers target medium-and high-throughput workflows, such as those found in hospitals and central laboratories. Such machines are large and expensive to own and operate. Their footprints, and cost-of-ownership make them inappropriate for low-throughput point-of-care environments, such as doctor offices and local clinics. Some smaller point-of-care immunoanlyzers use less sensitive techniques, such as absorbance and chromatography-based assays. These instruments are not only insensitive, but often imprecise, leading to unacceptable diagnostic errors. Small, point-of-care, bead-based chemiluminescent immunoassay instruments do exist. However, these instruments use single-use cartridges that contain the necessary reagents and disposables necessary to run a single assay. For instance, one such analyzer uses a disposable cartridge that comprises a pipette tip, a film-piercing trocar, a sheath to protect a magnet from contamination, an opaque read-well, and a series of 11 liquid wells containing the reagents needed for the run. The complexity of the consumable increases the per-sample cost of ownership. This is unacceptable in a point-of-care market where doctors are routinely constrained by factors such as insurance reimbursement rates. There is therefore an urgent need for a point-of-care immunoanlyzer that minimizes the consumable complexity and cost, while maintaining the bead-based chemiluminescent assay format that has become the gold-standard of sensitivity and accuracy in clinical diagnostics. The present disclosure is directed to overcoming one or more of these above referenced challenges. SUMMARY This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter. According to an aspect of the present disclosure, an analytical module is provided. The analytical module comprises a rigid base, a motor rigidly attached to the rigid base, and a cylindrical housing rigidly attached to the rigid base and having a hole in a bottom through which a shaft of the motor protrudes. The housing includes one or more magnets and a sensor. The analytical module further comprises a shuttle attached to a rotating shaft of the motor, the shuttle being nested within the housing and free to rotate within the housing. The shuttle is configured to hold one or more reaction vessels, and comprises a flag configured to interact with the sensor on the housing to define a unique position. The analytical module also comprises a detector connected to the housing and a shroud positioned so as to shield the detector from ambient light. According to other aspects of the present disclosure, the analytical module may include one or more of the following features. The motor may be driven back-and-forth to cause the shuttle containing the one or more reaction vessels to rotate back-and-forth and thereby cause a liquid within the reaction vessels to mix, and to cause particles within the reaction vessels to be resuspended. The motor may be driven back-and-forth at a frequency of between 1 and 20 cycles per second. The motor that causes the shuttle to oscillate back and forth for mixing may also be used to position the shuttle at precise locations in the housing. The analytical module may further include a double pipettor probe configured to interact with the one or more reaction vessels, the double pipettor probe including a first probe and a second probe. The analytical module may further include a wash manifold configured to translate up and down between two positions, the wash manifold having pairs of aspirate and dispense probes, each pair of probes being configured so that when the wash manifold is in one of its position, the probes are engaged with corresponding reaction vessels. The shuttle may be rotated between multiple unique positions in the housing, the positions including a reaction vessel load and reaction vessel unload position where one or more reaction vessels may be loaded and unloaded, a magnet-engagement position where the one or more reaction vessels abut ma