EP-4741801-A1 - AUTOMATED FLOW CYTOMETRY PREPARATION AND ACQUISITION SYSTEM, AND METHODS OF USE THEREOF

EP4741801A1EP 4741801 A1EP4741801 A1EP 4741801A1EP-4741801-A1

Abstract

Robotic systems for automated sample preparation are provided. Systems of interest include a plurality of sample processing modules, a plurality of robotic components integrated with the sample processing modules, a processor comprising memory operably coupled to the processor wherein the memory comprises instructions stored thereon, which when executed by the processor, cause the processor to control the sample processing modules and the robotic components to: operate the sample processing modules and robotic components to prepare a plurality of samples for flow cytometric analysis, and an operable connection among the processor, the sample processing modules and the plurality of robotic components. Systems according to certain embodiments further include a flow cytometer, wherein the plurality of robotic components are further integrated with the flow cytometer, wherein the memory further comprises instructions stored thereon, which when executed by the processor, cause the processor to control the sample processing modules, the robotic components and the flow cytometer to: load each prepared sample of the plurality of samples into the flow cytometer, and operate the flow cytometer to analyze each prepared sample of the plurality of samples, wherein the operable connection operably connects the processor, the sample processing modules, the flow cytometer and the plurality of robotic components. Methods of use and configuration or design of systems are also provided.

Inventors

Valeryevich Bashratyan, Roman
Ann Chuddy, Jennifer
de Vera, Kiera
Gayle Birmingham, Katherine

Assignees

Becton, Dickinson and Company

Dates

Publication Date: 20260513
Application Date: 20251111

Claims (15)

A robotic system for automated sample preparation, the system comprising: a plurality of sample processing modules; a plurality of robotic components integrated with the sample processing modules; a processor comprising memory operably coupled to the processor wherein the memory comprises instructions stored thereon, which when executed by the processor, cause the processor to control the sample processing modules and the robotic components to: operate the sample processing modules and robotic components to prepare a plurality of samples for flow cytometric analysis; and an operable connection among the processor, the sample processing modules and the plurality of robotic components.
The system of claim 1, further comprising: a flow cytometer, wherein the plurality of robotic components are further integrated with the flow cytometer, wherein the memory further comprises instructions stored thereon, which when executed by the processor, cause the processor to control the sample processing modules, the robotic components and the flow cytometer to: load each prepared sample of the plurality of samples into the flow cytometer; and operate the flow cytometer to analyze each prepared sample of the plurality of samples, wherein the operable connection operably connects the processor, the sample processing modules, the flow cytometer and the plurality of robotic components.
The system according to any of the preceding claims, wherein the system is configured to automatically prepare a plurality of samples for flow cytometric analysis.
The system according to any of the preceding claims, wherein the system is configured to automatically and continuously prepare a plurality of samples for flow cytometric analysis.
The system according to any of the preceding claims, wherein the system is configured to prepare a plurality of samples for flow cytometric analysis in a walkaway format.
The system according to any of the preceding claims, wherein the system is a robotic system for automated sample preparation and flow cytometric analysis.
The system according to any of the preceding claims, wherein the instructions comprise one or more of: scheduling software, software for defining liquid handling parameters and software for defining system setup.
The system according to any of the preceding claims, wherein the plurality of sample processing modules are configured to prepare samples for flow cytometric analysis.
The system according to any of the preceding claims, wherein the plurality of sample processing modules comprises standalone lab equipment.
The system according to any of the preceding claims, wherein the plurality of modules comprises one or more of: an antibody dilution module, a cell staining module, a sample washing module, a sample resuspension module, a sample movement module and a sample analysis module.
The system according to any of the preceding claims, wherein the plurality of modules comprises one or more of: an incubator, a storage unit, a chiller, a plate washer, a well washer, a compressor, a vacuum pump, a static nest, a bottle, a flow cytometer, a plate rotator, a barcode scanner, plate storage, a centrifuge, a handover nest, an automated liquid handling platform, a pipettor, a sample receiving area, a reagent receiving area and a waste receiving area.
The system according to any of the preceding claims, wherein the plurality of modules comprises a flow cytometer configured to perform flow cytometric analysis on a sample prepared by the system.
The system according to any of the preceding claims, further comprising a user interface.
The system according to any of the preceding claims, further comprising a network interface.
A method of preparing samples for flow cytometric analysis, the method comprising: introducing a plurality of samples into a first sample processing module of a plurality of sample processing modules of a system, wherein the system comprises: the plurality of sample processing modules; a plurality of robotic components integrated with the sample processing modules; a processor comprising memory operably coupled to the processor wherein the memory comprises instructions stored thereon, which when executed by the processor, cause the processor to control the sample processing modules and the robotic components to: operate the sample processing modules and robotic components to prepare a plurality of samples for flow cytometric analysis; and an operable connection among the processor, the sample processing modules and the plurality of robotic components; providing sample preparation instructions to the system; and activating the system to automatically prepare samples according to the sample preparation instructions.

Description

CROSS-REFERENCE TO RELATED APPLICATION Pursuant to 35 U.S.C. § 119(e), this application claims priority to the filing date of United States Provisional Patent Application Serial No. 63/719,515 filed November 12, 2024, the disclosure of which application is incorporated herein by reference in its entirety. INTRODUCTION The characterization of analytes in biological fluids has become an important part of biological research, medical diagnoses and assessments of overall health and wellness of a patient. Detecting analytes in biological fluids, such as human blood or blood derived products, can provide results that may play a role in determining a treatment protocol of a patient having a variety of disease conditions. Flow cytometry is a technique used to characterize and often times sort biological material, such as cells of a blood sample or particles of interest in another type of biological or chemical sample. A flow cytometer typically includes a sample reservoir for receiving a fluid sample, such as a blood sample, and a sheath reservoir containing a sheath fluid. The flow cytometer transports the particles (including cells) in the fluid sample as a cell stream to a flow cell, while also directing the sheath fluid to the flow cell. To characterize the components of the flow stream, the flow stream is irradiated with light. Variations in the materials in the flow stream, such as morphologies or the presence of fluorescent labels, may cause variations in the observed light and these variations allow for characterization and separation. To characterize the components in the flow stream, light must impinge on the flow stream and be collected. Light sources in flow cytometers can vary and may include one or more broad spectrum lamps, light emitting diodes as well as single wavelength lasers. The light source is aligned with the flow stream and an optical response from the illuminated particles is collected and quantified. Isolation of biological particles has been achieved by adding a sorting or collection capability to flow cytometers. Particles in a segregated stream, detected as having one or more desired characteristics, are individually isolated from the sample stream by mechanical or electrical removal. A common flow sorting technique utilizes drop sorting in which a fluid stream containing linearly segregated particles is broken into drops. The drops containing particles of interest are electrically charged and deflected into a collection tube by passage through an electric field. Typically, the linearly segregated particles in the stream are characterized as they pass through an observation point situated just below the nozzle tip. Once a particle is identified as meeting one or more desired criteria, the time at which it will reach the drop break-off point and break from the stream in a drop can be predicted. Ideally, a brief charge is applied to the fluid stream just before the drop containing the selected particle breaks from the stream and then grounded immediately after the drop breaks off. The drop to be sorted maintains an electrical charge as it breaks off from the fluid stream, and all other drops are left un-charged. Typically, before a sample can be characterized or otherwise analyzed by a flow cytometer, the sample, such as a biological sample, requires preparation, including, for example, sample staining and/or sample washing. Such preparation steps can be time and labor intensive, i.e., such that an operator or technician is required to conduct or oversee such aspects of sample preparation. Further, such preparation steps, when conducted or overseen by a human technician, can introduce variation into the resulting flow cytometric analysis of such prepared samples. SUMMARY Thus, the inventors have realized that there is a need for a robotic system that enables fully automated sample preparation and fully automated flow cytometric analysis. In particular, there is a need for a modular robotic system that permits automated sample preparation of flow cytometry assays to provide a walk-away solution for sample staining, washing and acquisition with the ability to stagger multiple unique experiments simultaneously. Embodiments of the present disclosure address this need. Embodiments of the present disclosure address limitations of existing techniques by providing a fully walk-away solution, i.e., a system configured such that flow cytometric samples can be prepared and analyzed without direct user supervision or manipulation. Such improvements of existing techniques may, among other things, improve sample preparation consistency and accuracy as well as improve efficiency and cost-effectiveness of sample preparation and flow cytometric analysis of prepared samples. Aspects of the present disclosure include robotic systems for automated sample preparation. Systems according to certain embodiments include a plurality of sample processing modules, a plurality of robotic components integrated with t