WO2025171036A1 - Automation of biopsy analysis systems and methods - Google Patents

Abstract

The present invention provides a system for automated biopsy analysis. The system includes a biopsy needle holder and delivery system configured to secure a biopsy needle, a sample transfer system configured to transfer a biopsy sample from the biopsy needle to a well of a multi-well plate, a liquid handling system configured to dispense and aspirate liquids to and from the well of the multi-well plate, an optical measurement system configured to measure fluorescent signals from the well, and a control system configured to control operations of the biopsy needle holder and delivery system, the sample transfer system, the liquid handling system, and the optical measurement system. The system enables automated processing and analysis of biopsy samples, improving efficiency and reproducibility in metabolic rate determination and other tissue analyses.

Description

AUTOMATION OF BIOPSY ANALYSIS SYSTEMS AND METHODS

INVENTORS: Benjamin Renquist, Kyle Kentch, Baker Logan, Tyler Shaw, Katrina Detmer

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63/550,566, titled "Automation of Biopsy Analysis Systems and Methods," filed February 6, 2024, which is hereby incorporated by reference in its entirety.

FIELD OF INVENTION

[0002] The present invention relates to automated systems for biological sample analysis, and more particularly to an automated biopsy analysis system and method for assessing the metabolic rate of an animal through automated processing and analysis of tissue biopsies in various settings, including on-site farm testing.

BACKGROUND

[0003] In the field of metabolic rate testing, particularly in veterinary medicine and animal research, accurate assessment of tissue samples is crucial for understanding animal health and metabolism. Traditionally, the process of obtaining and analyzing tissue biopsies has been largely manual, involving several discrete steps that are time-consuming and prone to variability.

[0004] Conventional approaches to biopsy analysis typically begin with the manual collection of tissue biopsies using specialized needle tools. Once obtained, the tissue biopsies must be carefully transferred to analysis plates, such as 96-well plates, for further processing. The transfer process introduces opportunities for human error and potential contamination of the samples.

[0005] After placement of the tissue biopsies in the analysis plate, the tissue biopsies require preparation with various media to preserve their viability and enable accurate metabolic analysis. In prior systems, this preparation step is often performed manually or with separate, nonintegrated liquid handling devices, which can lead to inconsistencies in sample preparation and affect the reliability of test results.

[0006] Incubation of prepared samples is another critical step in the analysis process. Typically, the incubation of the samples is performed in standard incubators with no direct integration with the sampling or analysis devices. This step necessitates additional handling of samples, potentially introducing temperature variations that can alter metabolic readings.

[0007] The detection and measurement of metabolic rates often rely on fluorescence-based assays, which require sophisticated optics to measure fluorescent signals from the processed tissue samples. Traditionally, these optics are part of separate, standalone readers or microscopes, requiring yet another transfer of the sample and introducing further risks of sample degradation and contamination.

[0008] Throughout the entire process, maintaining sterility presents a significant challenge, particularly when samples are handled outside of controlled laboratory environments, such as in on-site farm testing scenarios. Systems that incorporate sterility measures often do so in a manner that is not integrated with the biopsy and analysis process, thereby requiring additional steps and equipment.

[0009] Data collection and analysis in conventional systems typically involve manual recording of incubation times, sample handling schedules, and measurement results. This approach is not only labor-intensive but is also susceptible to human error, potentially leading to inaccuracies in data interpretation and reporting.

[0010] The segmented nature of these processes, requiring significant human intervention, is subject to risks of error, contamination, and variability. This non-integrated approach often results in a slow, laborious process that is not conducive to high-throughput environments or situations requiring rapid, on-site analysis.

[0011] There is a growing need for more efficient, accurate, and automated methods of biopsy analysis as research in animal metabolism and health continues to advance.

SUMMARY

[0012] 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.

[0013] The embodiments are for an integrated, automated system that streamlines the process of obtaining and analyzing tissue biopsies.

[0014] Its primary goal is to determine the metabolic rate of animals and perform other types of tissue analysis in a highly efficient, precise, and sterile manner.

[0015] It is an object of the present invention to increase efficiency by automating the traditionally manual steps involved in biopsy analysis, such as tissue extraction, transfer, media addition, and data collection, reducing the time and labor required. [0016] It is another object of the present invention to enhance precision by eliminating variability and errors caused by human intervention through the use of automated controls, advanced optics for fluorescence detection, and precise liquid handling systems.

[0017] It is another object of the present invention to ensure sterility by incorporating ultraviolet (UV) sterilization and positive pressure systems to maintain a sterile environment throughout the biopsy handling and analysis processes, crucial for reliable results.

[0018] It is another object of the present invention to enable high-throughput testing by providing a solution capable of processing multiple samples simultaneously, making it suitable for research and commercial applications.

[0019] It is yet another object of the present invention to facilitate on-site testing by designing a system that is portable and self-contained, which allows for use in various settings, including farms or other remote environments.

[0020] It is yet another object of the present invention to improve data management, integrate software for real-time control, data analysis, and reporting, ensuring traceability, reproducibility, and rapid interpretation of results.

[0021] The embodiments of the present invention aim to address the limitations of traditional biopsy analysis methods by combining precision, automation, and versatility, making it a valuable tool in veterinary medicine, animal research, and broader biotechnology applications.

[0022] According to an aspect of the present invention, a system for automated biopsy analysis is provided. The system includes a biopsy needle holder and delivery system configured to secure a biopsy needle. The system includes a sample transfer system configured to transfer a biopsy sample from the biopsy needle to a well of a multi-well plate. The system includes a liquid handling system configured to add and remove liquids from the well. The system includes an optical measurement system configured to measure fluorescent signals/reagents from the well. The system includes a control system configured to coordinate or control operations of the biopsy needle holder and delivery system , the sample transfer system, the liquid handling system, and the optical measurement system.

[0023] According to other aspects of the present invention, the system may include one or more of the following features. The sample transfer system may comprise a compressed gas ejection system configured to eject the biopsy sample from the biopsy needle using a burst of compressed gas. The liquid handling system may comprise a plurality of pumps configured to dispense and aspirate liquids to and from the well. The optical measurement system may comprise a laser configured to excite fluorescent markers/reagents in the biopsy sample and a photodetector configured to detect fluorescent emissions from the excited markers. The system may further comprise a sterilization system configured to sterilize components of the system using ultraviolet light. The system may further comprise a temperature control system configured to maintain the biopsy sample at a predetermined temperature during analysis. The temperature control system may comprise thermoelectric coolers and a temperature sensor, and the control system may be further configured to monitor a temperature of the biopsy sample using the temperature sensor, compare the monitored temperature to the predetermined temperature, and adjust the thermoelectric coolers to maintain the biopsy sample at the predetermined temperature.

[0024] According to another aspect of the present invention, a method for automated biopsy analysis is provided. The method includes securing a biopsy needle containing a biopsy sample in a biopsy needle holder and delivery system. The method includes transferring the biopsy sample from the biopsy needle to a well of a multi-well plate. The method includes adding a liquid to the well containing the biopsy sample. The method includes incubating the biopsy sample. The method includes measuring a fluorescent signal from the well. The method includes analyzing the measured fluorescent signal to determine a characteristic of the biopsy sample. [0025] According to other aspects of the present invention, the method may include one or more of the following features. Transferring the biopsy sample may comprise ejecting the sample from the biopsy needle using a burst of compressed gas. Adding the liquid may comprise dispensing the liquid using a pump-based liquid handling system. The method may further comprise sterilizing components of a biopsy analysis system using ultraviolet light prior to securing the biopsy needle. The method may further comprise maintaining the biopsy sample at a predetermined temperature during incubation using a temperature control system. Maintaining the biopsy sample at the predetermined temperature may comprise monitoring a temperature of the biopsy sample using a temperature sensor, comparing the monitored temperature to the predetermined temperature, and adjusting thermoelectric coolers to maintain the biopsy sample at the predetermined temperature. The method may further comprise removing the liquid from the well after incubation, adding a fluorescent reagent to the well, exciting the fluorescent reagent using a laser, detecting fluorescent emissions from the excited reagent using a photodetector, analyzing the detected fluorescent emissions to determine a metabolic rate of the biopsy sample, and generating a report indicating the determined metabolic rate.

[0026] According to another aspect of the present invention, a non-transitory computer- readable medium storing instructions is provided. When executed by a processor, the instructions cause the processor to perform operations for automated biopsy analysis. The operations include controlling a biopsy needle holder and delivery system to secure a biopsy needle. The operations include directing a sample transfer system to transfer a biopsy sample from the biopsy needle to a well of a multi-well plate. The operations include managing a liquid handling system to add and remove liquids from the well. The operations include coordinating an optical measurement system to measure fluorescent signals from the well. The operations include processing the measured fluorescent signals to determine a characteristic of the biopsy sample.

[0027] According to other aspects of the present invention, the operations may include one or more of the following features. The operations may further comprise controlling a sterilization system to sterilize components of a biopsy analysis system using ultraviolet light prior to securing the biopsy needle. Directing the sample transfer system may involve activating a compressed gas ejection system to eject the biopsy sample from the biopsy needle using a burst of compressed gas. The operations may further comprise controlling a temperature control system to maintain the biopsy sample at a predetermined temperature during analysis.

Controlling the temperature control system may comprise monitoring a temperature of the biopsy sample using a temperature sensor, comparing the monitored temperature to the predetermined temperature, and adjusting thermoelectric coolers to maintain the biopsy sample at the predetermined temperature. The operations may further comprise controlling the liquid handling system to remove a first liquid from the well after incubation and add a fluorescent reagent to the well, coordinating the optical measurement system to excite the fluorescent reagent using a laser and detect fluorescent emissions from the excited reagent using a photodetector, analyzing the detected fluorescent emissions to determine a metabolic rate of the biopsy sample, generating a report indicating the determined metabolic rate, managing data storage to record the measured fluorescent signals, the determined metabolic rate, and associated metadata, controlling a positive pressure system to maintain a sterile environment within the biopsy analysis system, and coordinating a user interface to display real-time analysis progress and results to a user.

[0028] The present invention provides an integrated system (automated biopsy analysis system) that automates the process of handling, preparing, and analyzing tissue biopsy samples. The automated biopsy analysis system may combine multiple components to streamline the workflow from sample collection to data analysis, potentially reducing human error and increasing efficiency in metabolic rate testing and other types of biopsy analysis.

[0029] In some cases, the automated biopsy analysis system may include several key subsystems working in concert. These subsystems may include mechanisms for securing and manipulating biopsy needles, transferring tissue samples to analysis wells, handling various liquids required for sample preparation and analysis, measuring fluorescent signals from prepared samples, and coordinating the operations of all these components.

[0030] The automated biopsy analysis system may be designed to maintain sterility throughout the analysis process, control environmental conditions such as temperature, and provide precise measurements for metabolic rate determination or other analytical purposes. By automating these processes, the automated biopsy analysis system may offer advantages in terms of consistency, speed, and reliability compared to manual methods of biopsy analysis.

[0031] In some implementations, the automated biopsy analysis system may be particularly suited for applications in veterinary medicine, animal research, or other fields where high- throughput metabolic testing or tissue analysis may be required. The automated biopsy analysis system may be capable of processing multiple samples in sequence, potentially increasing the efficiency of research or diagnostic workflows. [0032] The foregoing general description of the illustrative embodiments and the following detailed description thereof are merely exemplary aspects of the teachings of this invention and are not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

[0033] FIG. 1 illustrates a block diagram of an automated biopsy analysis system, in accordance with one embodiment of the present invention.

[0034] FIG. 2 illustrates a perspective view of a biopsy needle holder and delivery system of the automated biopsy analysis system, in accordance with one embodiment of the present invention.

[0035] FIG. 3 illustrates an enlarged view of the biopsy needle holder and delivery system showing a mounting plate having brackets and mounting holes, in accordance with one embodiment of the present invention.

[0036] FIG. 4A, FIG. 4B and FIG. 4C illustrate a side perspective view, a top perspective view and a front view, respectively of a liquid handling system of the automated biopsy analysis system, in accordance with one embodiment of the present invention.

[0037] FIG. 5 illustrates bottle assemblies housed in a bottle housing unit, in accordance with one embodiment of the present invention.

[0038] FIG. 6 illustrates dispensing tips positioned above a multi-well plate, in accordance with one embodiment of the present invention.

[0039] FIG. 7 illustrates a block diagram of a control system of the automated biopsy analysis system, in accordance with one embodiment of the present invention. [0040] FIG. 8 illustrates a process flow diagram for the automated biopsy analysis system, in accordance with one embodiment of the present invention.

[0041] FIG. 9 illustrates a subsystem diagram of the automated biopsy analysis system, in accordance with one embodiment of the present invention.

[0042] FIG. 10A and FIG. 10B illustrate an optical subsystem, in accordance with one exemplary embodiment of the present invention.

[0043] FIG. 11 illustrates a single detector optical setup for the automated biopsy analysis system, in accordance with one embodiment of the present invention.

[0044] FIG. 12 illustrates an optical system diagram showing a dual detector setup for fluorescence detection, in accordance with one embodiment of the present invention.

[0045] FIG. 13 illustrates a space requirements diagram for an optical detection system, in accordance with one embodiment of the present invention.

[0046] FIG. 14A, FIG. 14B and FIG. 14C illustrate orthogonal views of a movement subsystem for the automated biopsy analysis system, in accordance with one embodiment of the present invention.

[0047] FIG. 15 illustrates an electrical system diagram for the automated biopsy analysis system, in accordance with one embodiment of the present invention.

[0048] FIG. 16A and FIG. 16B illustrate a perspective view, and a front view, respectively of a liquid handling subsystem for an automated biopsy analysis system, in accordance with another embodiment of the present invention.

[0049] FIG. 17 illustrates an interior perspective view of a movement subsystem, in accordance with one exemplary embodiment of the present invention. DETAILED DESCRIPTION

[0050] The invention now will be described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. This invention may however be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0051] It will be understood that when an element is referred to as being “on” another element, it can be directly on the other element or intervening elements may be present therebetween. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items.

[0052] It will be understood that, although the terms first, second, third etc. may be used herein to describe various elements, components, regions, layers, and/or sections, these elements, components, regions, layers, and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer, and/or section from another element, component, region, layer, and/or section.

[0053] It will be understood that the elements, components, regions, layers and sections depicted in the figures are not necessarily drawn to scale.

[0054] The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting of the invention. As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” or “includes” and/or “including” when used in this specification, specify the presence of stated features, regions, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and/or groups thereof.

[0055] Furthermore, relative terms, such as “lower” or “bottom,” “upper” or “top,” “left” or “right,” “above” or “below,” “front” or “rear,” may be used herein to describe one element’s relationship to another element as illustrated in the Figures. It will be understood that relative terms are intended to encompass different orientations of the device in addition to the orientation depicted in the Figures.

[0056] Unless otherwise defined, all terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present invention, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0057] Exemplary embodiments of the present invention are described herein with reference to idealized embodiments of the present invention. As such, variations from the shapes of the illustrations as a result, for example, of manufacturing techniques and/or tolerances, are to be expected. The numbers, ratios, percentages, and other values may include those that are ±5%, ±10%, ±25%, ±50%, ±75%, ±100%, ±200%, ±500%, or other ranges that do not detract from the spirit of the invention. The terms about, approximately, or substantially may include values known to those having ordinary skill in the art. If not known in the art, these terms may be considered to be in the range of up to ±5%, ±10%, or other value higher than these ranges commonly accepted by those having ordinary skill in the art for the variable disclosed. Thus, embodiments of the present invention should not be construed as limited to the particular shapes of regions illustrated herein but are to include deviations in shapes that result, for example, from manufacturing. The invention illustratively disclosed herein suitably may be practiced in the absence of any elements that are not specifically disclosed herein. All patents, patent applications and non-patent literature cited through this Specification are hereby incorporated by reference in their entireties. References cited in an Information Disclosure Statement should not be construed as an admission that the cited reference comes from an area that is analogous or directly applicable to the invention, but rather that the reference is being cited out of an abundance of caution.

[0058] The invention is a self-contained, automated system that facilitates the process of obtaining and analyzing a tissue biopsy to determine the metabolic rate of an animal or any other analysis of a biopsy including the measurement of any metabolite, protein, or compound.

[0059] Referring to Figures, FIG. 1 shows a block diagram of an automated biopsy analysis system or simply “system” 10 that facilitates the process of obtaining and analyzing a tissue biopsy to determine the metabolic rate of an animal or any other analysis of a biopsy, in accordance with one embodiment of the present invention. System 10 includes a biopsy needle holder and delivery system 12, a biopsy needle sterilization system 14, an air jet system (or sample transfer system) 16, a liquid handling system 18, and an optical measurement system 20, a sterilization system 22, and a control system 24.

[0060] FIG. 2 shows biopsy needle holder and delivery system 12, in accordance with one embodiment of the present invention. Biopsy needle holder and delivery system 12 provides a means for securing a biopsy needle 30 and transferring a biopsy sample to a multi-well plate 46 (FIG. 6) for analysis. As shown in FIG. 2, biopsy needle holder and delivery system 12 includes a vertical mounting frame 32 constructed from aluminum extrusions with a central channel 32. Biopsy needle holder and delivery system 12 includes a mounting plate 34 attached to vertical mounting frame 32. Mounting plate 34 includes brackets 36 having mounting holes 38. Brackets 36 receive biopsy needle 30. FIG. 3 shows the feature of mounting plate 34 having brackets 36 and mounting holes 38, in accordance with one embodiment of the present invention.

[0061] Biopsy needle holder and delivery system 12 encompasses a biopsy needle holder 40 designed to securely grip and position a biopsy needle biopsy needle 30. Biopsy needle holder 40 extends from the bottom bracket 36. In some cases, biopsy needle holder 40 may have adjustment capabilities to accommodate different needle sizes. Biopsy needle holder 40 ensures proper alignment and stability of biopsy needle 30 during sample transfer operations.

[0062] In the present invention, biopsy needle holder and delivery system 12 mechanically advances biopsy needle 30 toward the well and exposes the biopsy automatically, allowing for the removal of tissue samples from biopsy needle 30 and placement of the biopsy into wells. It should be understood that biopsy needle holder and delivery system 12 is an automated mechanical device designed to securely hold and manipulate biopsy needle 30. In some implementations, biopsy needle holder and delivery system 12 is controlled by a computer program (control system 24) to advance and retract biopsy needle 30 as necessary, ensuring precise entry and retraction without manual intervention. Further, biopsy needle holder 40 is equipped with sensors (not shown) to detect the proper positioning of biopsy needle 30 when a biopsy is taken and when it is to be exposed for further processing.

[0063] After collecting the biopsy, biopsy needle 30 may have bacterial contamination. In order to sterilize biopsy needle 30, biopsy needle sterilization system 14 is utilized. As biopsy needle 30 enters the sterile portion of system 10 where the plates are housed and analyses occur, biopsy needle 30 is sterilized with a ring of ultraviolet (UV) lights (nor shown). This is essential to ensure that biopsy needle 30 does not introduce contamination to the sterile part of system 10. Subsequently, system 10 employs air jet system 16 i.e., a jet of air to transfer the biopsy sample from biopsy needle 30 to a well of multi-well plate 46 (FIG. 6). It should be understood that air jet system 16 may also be referred to as a sample transfer system or sample transfer mechanism. In some implementations, the sample transfer system may comprise a compressed gas ejection system. The compressed gas ejection system may be configured to eject the biopsy sample from biopsy needle 30 using a burst of compressed gas. Air jet system 16 allows for controlled and precise transfer of the biopsy sample without mechanical contact, helping to maintain sample integrity.

[0064] In some implementations, system 10 includes a vertical linear guide system 42 with rails and bearings to enable precise up-and-down movement of biopsy needle 30. This vertical movement capability allows for accurate positioning of biopsy needle 30 relative to the multiwell plate 46 during sample transfer operations. Mechanical components for controlled vertical movement may include linear actuators or positioning elements. As specified above, system 10 includes biopsy needle sterilization system 14 for sterilizing biopsy needle 30. The UV sterilization of biopsy needle 30 helps to maintain aseptic conditions and reduce the risk of sample contamination during the transfer process.

[0065] In some examples, air jet system 16 may include a camera (not shown) for imaging the sample. The camera may allow for visual confirmation of successful sample transfer and may provide documentation of the sample condition before analysis.

[0066] In one implementation, biopsy needle sterilization system 14 and air jet system 16 are integrated in biopsy needle holder and delivery system 12. The construction of the biopsy needle holder and delivery system 12 is made such that biopsy needle holder and delivery system 12 provides stability while maintaining accessibility for loading and unloading of biopsy needle 30. The design of vertical mounting frame 32 allows for precise alignment and movement control during the biopsy process, facilitating accurate and repeatable sample transfer operations. [0067] Liquid handling system 18 of system 10 is designed to precisely add and remove various liquids from the wells of multi-well plate 46 during the analysis process. FIG. 4A, FIG. 4B and FIG. 4C show a side perspective view, a top perspective view and a front view, respectively of liquid handling system 18, in accordance with one embodiment of the present invention. Liquid handling system 18 may comprise multiple peristaltic pumps 50 mounted on an elevated platform section 52. Pumps 50 may be arranged in a linear configuration and connected via tubing 54 for fluid transfer operations. The arrangement of multiple pumps 50 may allow for the handling of different types of liquids, such as addition and removal of media and reagents from the wells containing the tissue sample. The arrangement of multiple pumps 50 allows for the precise dispensation of small volumes, necessary for laboratory style assays. Liquid handling system 18 is also designed to prevent cross-contamination between samples and reagents, ensuring the integrity of each test.

[0068] Liquid handling system 18 may incorporate bottle assemblies for storing and dispensing various liquids. FIG. 5 shows bottle assemblies 60 housed in a bottle housing unit 62. Each bottle 60 includes a bottle cap 64 with integrated septa (not shown), featuring screw-top caps with septum inserts. Bottle housing unit 62 is made of a stainless steel enclosure containing multiple bottles 60 arranged in a row, each sealed with caps 64. This configuration may help maintain the sterility and integrity of the liquids used in the analysis process. [0069] FIG. 4C illustrates how liquid handling system 18 may integrate solenoid valves 66 into its design. Solenoid valves 66 are arranged in a row and mounted to a metallic mounting block 68, may be connected via tubing 54 for fluid transfer. Solenoid valves 66 may allow for precise control of liquid flow throughout system 10, enabling the addition and removal of specific volumes of liquids as required by the analysis protocol.

[0070] In some implementations, liquid handling system 18 may be used to add liquids to wells containing biopsy samples. As shown in FIG. 6, system 10 may include dispensing tips 70 positioned above multi-well plate 46. Dispensing tips 70 may be arranged in a linear configuration and positioned directly above individual wells of the multi-well plate 46, allowing for precise dispensing of liquids into each well.

[0071] Liquid handling system 18 may be capable of adding various types of liquids to the wells. In some cases, this may include adding a fluorescent reagent to the wells for analysis purposes. System 10 may also be configured to remove liquids from the wells after incubation periods, allowing for multi-step analysis protocols.

[0072] In some implementations, liquid handling system 18 may be managed by control system 24 to coordinate the addition and removal of liquids from the wells of multi -well plate 46. This management may include controlling liquid handling system 18 to remove a first liquid from the wells after incubation and subsequently add a fluorescent reagent to the wells for analysis.

[0073] The pump-based liquid handling system 18 may provide precise control over liquid dispensing and aspiration. This precision may be crucial for maintaining consistent sample preparation and analysis conditions across multiple wells and samples. By automating these liquid handling processes, system 10 may help reduce variability and potential errors associated with manual liquid handling techniques.

[0074] As specified above, system 10 includes optical measurement system 20. Optical measurement system 20 encompasses optics (lasers, mirrors, lenses, filters, and photosensitive detectors) to measure fluorescent signals emitted from the well after excitation by a laser at a specific wavelength. Optics can be adapted to measure luminescence or absorbance for alternate assays. System 10 is calibrated to differentiate between various fluorescent reagents, luminescence, or absorbance used in assays. Optical measurement system 20 and components therein are explained in greater detail in the later part of the description.

[0075] In some implementations, system 10 employs sterilization system 22 to sterilize system 10 and positive pressure to maintain a sterile environment suitable for sample processing. To maintain a sterile environment, system 10 incorporates ultraviolet (UV) light sterilization along with positive pressure airflow. The UV light ensures that the surface of the biopsy needle, as well as the interior of system 10 where the samples are processed, are free from microbial contamination. The positive pressure helps to keep airborne contaminants out of system 10, further safeguarding the sterility of the process.

[0076] Control system 24 is configured to manage specific incubation times and automate the reporting of measurement data, allowing for scheduled sample handling. FIG. 7 shows a block diagram of control system 24, in accordance with one embodiment of the present invention. Control system 24 encompasses a processor 80 (e g., a central processing unit (CPU), a graphics processing unit (GPU), or both). Processor 80 electrically couples to a memory 82. Memory 82 includes a volatile memory and/or a non-volatile memory. Preferably, memory 82 stores software instructions or software programs that interact with the other devices/components within or remotely connected to system 10 as described below. In one implementation, processor 80 executes the instructions stored in memory 82 in any suitable manner. In one implementation, memory 82 stores digital data indicative of documents, files, programs. In one example, memory 82 acts as a database and stores and manages large amounts of structured and unstructured data, and they can be used to support a wide range of activities, including data storage, data analysis, and data management. Control system 24 includes a user interface 84, a display 86 (e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT)) and a transceiver 88. Transceiver 88 is configured to send or receive data from other devices connected to system 10.

[0077] In the present invention, control system 24 stores software instructions utilizing an advanced, user-friendly interface that automates the entire process from sample handling to data management. Control system 24 enables the user to input specific incubation times, manage the sequence of assay steps, and record the measurements. The software is also capable of handling complex data analysis, generating reports, and maintaining logs for traceability and reproducibility.

[0078] System 10 may follow a structured process flow 100 from setup to cleanup, as illustrated in FIG. 8. The structured process flow 100 may be divided into several main phases: Setup 102, Sample Input 104, Sample Incubation 106, NADH Measurement 108, Sample Dissolve 110, Deoxyribonucleic acid (DNA) Assay Prep (preparation) 112, DNA Measurement 114, and Cleanup 116. It should be noted that the specific details described represent just one possible embodiment of how the system may operate, and modifications to the process flow described herein fall within the scope of the present disclosure.

[0079] Setup phase 102 may involve several preparatory steps. At first, a user may insert new liquid bottles, waste containers and sample trays in system 10 (step 120). System 10 may perform UV sterilization of key components to maintain aseptic conditions (step 122) for about 20 minutes. Further, the user finishes connecting the bottles (step 124). System 10 primes liquid lines and removes any priming liquid from wells to ensure accurate fluid dispensing (step 126). In some cases, system 10 may add reagents to standards, and DNA assay to DNA standards (step 128) and measure the fluorescence of NADH and DNA standards to establish baseline readings for subsequent analyses (step 130). Further, system 10 notifies the user (step 132) indicating that system 10 is ready to receive samples.

[0080] During the Sample Input phase 104, a biopsy sample may be transferred from biopsy needle 30 to a well of multi-well plate 46. Here, the user inserts biopsy needle 30 (step 134) with sample biopsy. Further, system 10 sterilizes outside of biopsy needle 30 using UV light (step 136). In some implementations, this transfer may be accomplished using sample transfer system or air jet system 16 that employs air pulses to eject the sample from biopsy needle 30 (step 138). System 10 may move to the dispense station and then add 300uL basal media to the well containing the biopsy sample (step 140). Further, system 10 notifies the user to remove biopsy needle 30 (step 142) and user removes biopsy needle 30 (step 144). The sample input process may be repeated for multiple samples, as system 10 is capable of handling up to 88 samples in some configurations.

[0081] Following sample input 104, sample incubation phase 106 may begin after a predetermined waiting period, such as one hour. Here, system 10 may move to the aspiration station to remove basal liquid (step 146), and add NADH reagent liquid (step 148) at the dispense station. During sample incubation phase 106, system 10 may maintain the sample at a specific temperature to ensure optimal conditions for metabolic activity. [0082] After sample incubation phase 106, the NADH Measurement phase 108 may commence. In this phase, system 10 may employ optical measurement system 20 to measure fluorescent signals from the well (step 150). This may involve moving the sample to optical measurement system 20, exciting a fluorescent reagent using a 530 nm laser, and detecting fluorescent emissions using a photodetector or photodiode. System 10 may perform these measurements at regular intervals, such as once per hour for four hours (T0-T4), to track changes in metabolic activity over time.

[0083] Following the NADH measurements and a dissolution period of 4 hours or longer (step 108), the Sample Dissolve phase 110 may begin. In Sample Dissolve phase 110, system 10 moves to the aspiration station, and may remove the NADH reagent (step 152) and add a dissolving agent, such as KOH, to prepare the sample for DNA analysis (step 154).

[0084] The DNA Assay Prep phase 112 may then follow, where system 10 processes the dissolved tissue sample with DNA assay liquid. This prepares the sample for subsequent DNA measurements. System 10 may allow for a short waiting period, such as 2-5 minutes, before proceeding to the next phase. Here, system 10 moves to the aspiration station to remove about 250uL of dissolved tissue sample (step 156), further moves to the dispense station to add 250uL of DNA assay liquid to 50uL tissue sample (step 158).

[0085] In DNA Measurement phase 114, system 10 may again use optical measurement system 20 to measure fluorescent signals (step 160). In some cases, this may involve exciting the sample with a 480 nm laser and detecting emissions at 520 nm. Here, system 10 may process the measured fluorescent signals to determine characteristics of the biopsy sample. In some implementations, this may include analyzing the detected fluorescent emissions to determine a metabolic rate of the biopsy sample. [0086] Upon completion of the measurements and analysis, system 12 may generate a report indicating the determined metabolic rate or other relevant characteristics of the biopsy sample.

[0087] Finally, in the Cleanup phase 116, system 10 may remove remaining liquids from the wells and transfer them to a waste container, preparing the system for the next analysis cycle (step 162). System 10 may follow a specific process priority order for these operations, as indicated in FIG. 8, to optimize efficiency and maintain sample integrity.

[0088] This automated process flow may allow for efficient, consistent, and high-throughput analysis of biopsy samples, potentially reducing human error and increasing the speed and reliability of metabolic rate determinations and other biopsy analyses. The specific details and timings described represent one possible implementation, and the system may be configured to accommodate different protocols or analysis requirements as needed.

[0089] System 10 may comprise several interconnected subsystems, each performing specific functions to enable comprehensive biopsy analysis. FIG. 9 shows subsystems 200 having a stage subsystem 202, a liquid handling subsystem 204, a sample input 206, an optical 208, controls/electronics 210, and peripherals components or peripherals subsystem 212.

[0090] Stage subsystem 202 may include X-axis 220 and Y-axis 222 movement components, allowing for precise positioning of samples during analysis. Stage subsystem 202 may include X home switch 224 and Y home switch 226 for the X-axis 220 and Y-axis 222, respectively to enable calibration and homing of the movement components. In some implementations, stage subsystem 202 may incorporate temperature control elements 228, such as thermoelectric coolers (TECs) and temperature sensors 230, to maintain environmental conditions for biopsy samples. [0091] Liquid handling subsystem 204 may comprise multiple pumps for fluid management. These pumps may be configured to aspirate 232 and dispense 234 various liquids. Liquid handling subsystem 204 may also include pumps 236, Z-axis movement 238 capability with a Z- home switch 240 for accurate vertical positioning of dispensing components. Z-axis movement 238 enables system 10 to have the capability for vertical movement to position the liquid handling system 18 at the correct height above the assay plate for precise pipetting. Z-axis movement 238 design is optimized for minimal dead volume to conserve precious reagents and samples, and it would be easy to clean and maintain. The precise control of the “Liquid” part 204 is crucial for the accuracy and repeatability of the metabolic assays carried out by system 10.

Further, liquid handling subsystem 204 may also include pumps for dispensing liquids including basal media pump 242, NADH reagent pump 244, KOH pump 246, DNA assay liquid pump 248, and other solutions required for sample preparation and analysis.

[0092] Sample Input subsystem 206 may be responsible for introducing biopsy samples into system 10. Sample Input subsystem 206 may include a Q-axis mechanism 250 with a Q-home switch 252 for sample positioning. Q-axis mechanism 250 is a motorized component that allows for the precise positioning of biopsy needle 30 over the receptacle, such as a well in a 96-well plate 46. In some cases, Sample Input subsystem 206 may incorporate a UV sterilization system 254 for the needle, a camera 256 for monitoring, and a CO2 solenoid 258 for sample ejection. It should be understood that sample input subsystem 206 represents the interface where the biopsy sample is introduced into the automated testing apparatus. Sample input subsystem 206 is designed to ensure that the sample is placed precisely, handled gently, and kept sterile.

[0093] Optical subsystem 208 may be configured to measure fluorescent signals from wells containing biopsy samples. Optical subsystem 208 may include two lasers, first laser (laser 1) 260 and a second laser (laser 2) 262 with corresponding detectors 264, 266 (first detector (detector 1) and second detector (detector 2)) and dedicated power supplies 268, 270 for each laser unit 260. 262. In some implementations, optical subsystem 208 may utilize multiple lasers and detectors to enable measurement of different fluorescent signals. FIG. 10A and FIG. 10B show exemplary optical subsystem 208. Optical subsystem 208 includes lenses, mirrors, and possibly fiber optics, which direct the laser light to the samples and then guide the emitted fluorescence to the detectors. The design of optical subsystem 208 is focused on maximizing the accuracy, sensitivity, and reliability of the fluorescence measurements, which are critical for the determination of the metabolic rates in the biopsy samples.

[0094] Optical measurement system 20 of system 10 may be configured to measure fluorescent signals from wells containing biopsy samples. FIG. 11 illustrates a single detector optical setup 300 for the biopsy analysis system. This setup includes two lasers 302 operating at different wavelengths - a 480 nm laser and a 532 nm laser. Each laser 302 provides the specific wavelength of light required to excite the fluorescent dyes or markers within the samples. Each laser 302 is finely tunable to emit light at the precise wavelength needed for the assays performed. Lasers 302 may be positioned at the top of the optical arrangement, providing excitation sources for fluorescence measurements. Here, optical measurement system 20 employs mirrors and a dichroic mirror to direct the laser beams towards the sample area.

[0095] It should be understood that optical measurement system 20 may employ a series of mirrors and a dichroic mirror to direct and combine the laser beams. A mirror (M) 304 may be used to reflect the 480 nm laser beam, while a dichroic mirror (DM) 306 may combine it with the 532 nm laser beam reflected by another mirror (M) 308. This arrangement may allow for efficient use of both laser sources 302 within a single optical path. [0096] The combined beam path may lead to a sample area indicated at the bottom of the diagram. This sample area may correspond to the location of the multi-well plate containing biopsy samples for analysis.

[0097] The detection system may comprise a parabolic mirror (PM) 310 positioned to collect fluorescence emitted from a sample in a plate 311. This parabolic mirror 310 may be designed to efficiently gather light over a wide angle, maximizing the collection of fluorescent signals.

[0098] Two lenses 312, 314, designated as LI and L2, may be incorporated into the optical path to focus the collected light. These lenses 312, 314 may work in tandem to collimate and then focus the fluorescent emissions, optimizing the signal for detection.

[0099] An emission filter or optical filter 316 may be positioned between the second lens (L2) 314 and a detector 318. Detector 318 includes a photodetector or photodiode, capable of capturing fluorescent signals, receiving power that ensures sensitive and accurate signal detection and conversion. Emission filter or optical filter 316 is positioned in the path of the emitted light, such that it ensures only the desired wavelengths reach detector 318, enhancing the specificity and sensitivity of the measurements. Emission filter 316 may be crucial for isolating the specific wavelengths of interest from the fluorescent emissions while blocking unwanted light, including scattered excitation light.

[0100] The system may be designed with flexibility in mind, allowing for emission filter 316 to be changed either manually or through an automated swapper with software control. This feature may enable the system to adapt to different fluorescent markers or experimental requirements by matching the filter to the operating laser wavelength. [0101] A single detector may be used in this configuration to measure the filtered fluorescent signals. The use of a single detector, combined with switchable filters, may offer a balance between system complexity and versatility.

[0102] The optical setup may be designed to operate with one laser active at a time. This sequential activation of lasers may allow for measurements of different fluorescent signals from samples without the need for multiple detectors or complex beam-splitting optics.

[0103] The arrangement illustrated in FIG. 11 may provide several advantages for biopsy analysis. By utilizing a single detector with switchable filters and lasers, the system may offer flexibility in measuring various fluorescent markers while maintaining a relatively simple and compact optical design. This configuration may also facilitate easier alignment and calibration compared to multi-detector systems.

[0104] The use of parabolic mirror 310 for light collection may enhance the system's sensitivity by capturing a large portion of the emitted fluorescence. This may be particularly beneficial when dealing with small sample volumes or low concentration analytes in biopsy samples.

[0105] The optical path design, incorporating multiple mirrors and a dichroic mirror, may allow for efficient use of space within the apparatus. This compact arrangement may contribute to the overall miniaturization of the biopsy analysis system, potentially making it more suitable for use in various laboratory settings.

[0106] FIG. 12 illustrates an optical system diagram showing a dual detector setup 400 for fluorescence detection. System 10 may include two lasers 402 operating at different wavelengths - a 480 nm laser and a 532 nm laser. The laser beams may be directed using mirrors (M) 404, 406 and a dichroic mirror (DM) 408 arrangement. A parabolic mirror (PM) 410 may collect emitted light from samples, which may pass through a series of lenses. The system may incorporate two detectors - a 520 nm detector 412 and a 590 nm detector 414 - each with its own emission filter 416, 418. The optical path may include multiple mirrors labeled as M 404 406, dichroic mirrors labeled as DM 408, and a parabolic mirror labeled as PM 410. Two lenses, LI 420 and L2 422, may focus the light along the optical path. In some aspects, the system may operate with the lasers running sequentially rather than simultaneously.

[0107] The dual detector setup 400 may eliminate the need for moving components by using fixed emission filters positioned before each detector. This arrangement may allow for measurements of different fluorescent signals without physically swapping filters. In some implementations, the optical system may be configured to excite fluorescent markers in biopsy samples using the 480 nm and 532 nm lasers sequentially. The 520 nm and 590 nm detectors 412, 414 may then capture the resulting fluorescent emissions through their respective fixed emission filters. This configuration may enable rapid switching between different fluorescence measurements without mechanical filter changes.

[0108] The parabolic mirror (PM) 410 in the optical path may serve to efficiently collect emitted light over a wide angle from the sample area. This collected light may then be focused by lenses LI and L2 420, 422 onto the appropriate detector. The use of dichroic mirrors (DM) 408 may allow for selective reflection and transmission of different wavelengths, enabling the system to direct excitation light to the sample in a plate 424 and separate emission light to the detectors.

[0109] In some aspects, the dual detector setup 400 may provide advantages in terms of measurement speed and flexibility. By having dedicated detectors 412, 414 for different emission wavelengths, system 10 may be capable of rapidly switching between fluorescence measurements without the need for mechanical filter changes or realignment. This may be particularly beneficial for applications requiring analysis of multiple fluorescent markers or timesensitive measurements.

[0110] The optical system may be designed to minimize crosstalk between the two detection channels. The fixed emission filters 416, 418 positioned before each detector 412, 414 may help ensure that only the desired wavelengths reach each detector, potentially improving the accuracy and specificity of fluorescence measurements. In some implementations, control system 24 may coordinate the sequential activation of lasers and readout of detectors to further reduce potential interference between channels.

[0111] The arrangement of optical components shown in FIG. 12 may allow for a compact and efficient design. By using fixed optical elements and eliminating the need for moving parts in the emission path, the system may potentially offer improved reliability and reduced maintenance requirements compared to systems with mechanically switched filters. The dual laser excitation capability may provide flexibility in exciting a range of fluorescent markers, potentially expanding the types of assays that can be performed with the system.

[0112] FIG. 13 illustrates a space requirements diagram for an optical detection system 500. The diagram shows the spatial layout and dimensions of components in a dual -detector optical setup. The system includes two lasers 502 - a 480 nm laser and a 532 nm laser - each occupying a 3-inch by 6-inch space. Two detectors are incorporated: a 590 nm detector 504 and a 520 nm detector 506, with emission filters 508, 510 positioned adjacent to each detector 504, 506.

[0113] The optical path includes mirrors (M) 512, a dichroic mirror (DM) 514, and a parabolic mirror (PM) 516 arranged to direct and focus the laser beams. Two lenses (LI 518 and L2 520) are positioned along the beam path to focus the light onto a plate 522. The diagram indicates specific spacing requirements between components, with 2-inch gaps between mirrors and a 4-inch spacing for the lens arrangement.

[0114] In some aspects, the optics and detectors, excluding lasers, may require approximately 15 inches length by 4 inches width by 6 inches height above the microplate. The laser heads may need a minimum space of 6 inches length by 7 inches width by 2 inches height. The laser power supply units may each require a space of 6 inches length by 6 inches width by 4 inches height.

[0115] The optical path may terminate at a microplate platform represented at the bottom of the diagram. In some implementations, the parabolic mirror may be positioned to collect emitted light from the samples in the microplate wells.

[0116] The diagram provides detailed spatial information that may be useful for designing and assembling the optical detection system. The precise arrangement and spacing of components may allow for efficient collection and focusing of laser excitation light as well as emitted fluorescence from samples.

[0117] In some cases, the dual-laser configuration may enable excitation at two different wavelengths, potentially allowing analysis of multiple fluorescent markers. The use of two separate detectors with dedicated emission filters may allow for simultaneous or rapid sequential detection of different emission wavelengths.

[0118] The compact arrangement of optical components shown in the diagram may contribute to the overall miniaturization of the biopsy analysis system. This space-efficient design may make the system suitable for use in various laboratory settings where bench space may be limited. [0119] The specified dimensions and layout may provide guidance for integrating the optical detection system with other components of the automated biopsy analysis apparatus, such as the sample positioning stage and liquid handling systems. This integration may be important for achieving precise alignment between samples and the optical detection pathway.

[0120] Referring back to FIG. 9, Controls/Electronics subsystem 210 may serve as the central control unit for system 10. Controls/Electronics subsystem 210 may include a computer 272, a main board 272, an Ethernet switch 274, a touch screen interface 276, and various power supplies 280, 282, 284 operating at different voltages (24V, 12V, and +/-12V) to coordinate the operations of other subsystems. In some cases, Controls/Electronics subsystem 210 may manage data acquisition, processing, and storage related to biopsy analysis.

[0121] Peripherals subsystem 212 may encompass additional components that support the overall functionality of the apparatus. Peripherals subsystem 212 may include environmental control elements such as enclosure fans 288 and a positive pressure fan 288 for temperature regulation, UV sterilization systems, such as UV ballast/bulbs for maintaining sterility in different areas (area UV bulb 290, bottle UV bulb 291, and plate UV bulb 292), a temperature controller 293, and X/Y solenoids 294 and Z solenoid 295 for fluid control. Specifically, enclosure fans 288 enhance airflow, cooling the internal components to prevent overheating and ensure stable operation. Positive pressure fan 288 maintains a sterile environment inside system 10 by creating a pressure differential that prevents outside contaminants from entering. Area UV ballast/bulb 290 provides UV sterilization to the general area within system 10, ensuring a sterile environment for sample processing. Bottle UV bulb 291 sterilizes bottles containing liquids or reagents before they are used in the assays to prevent contamination. Plate UV bulb 292 sterilizes the assay plates to ensure that the samples are deposited into a sterile environment. [0122] In some implementations, control system 24 positions within Controls/Electronics subsystem 212 to coordinate operations across all subsystems. Control system 24 may manage the sequencing of operations, from securing a biopsy needle in Sample Input subsystem 206 to measuring fluorescent signals in Optical subsystem 208. Control system 24 may also regulate the liquid handling subsystem 204 to ensure precise addition and removal of liquids from sample wells.

[0123] The integration of subsystems 200 may allow for a streamlined and automated approach to biopsy analysis, potentially reducing manual intervention and enhancing consistency in sample processing and measurement. It should be noted that the specific details described represent just one possible embodiment of the system, and additional embodiments with different configurations or components may be possible.

[0124] Additionally, system 10 may include a movement subsystem 600 designed to provide precise positioning and control of various components during the analysis process. FIGS. 14A, 14B and 14C show movement subsystem 600, in accordance with one embodiment of the present invention. Movement subsystem 600 includes an aluminum frame structure 602 with linear motion components arranged in an X-Y configuration. This configuration may allow for controlled movement in two dimensions, enabling accurate positioning of samples and other components within the apparatus.

[0125] Movement subsystem 600 may incorporate stepper motors 604 for driving the motion control components. As can be seen in FIG. 14A, stepper motor 604 mounts on one end of frame structure 602, connected to motion control components. These motors 604 may provide precise control over movement of the subsystem 600, allowing for accurate positioning of samples and other elements during the analysis process. [0126] Linear rails 606 and bearings may be included in movement subsystem 600 to enable smooth and precise motion along both axes. Movement subsystem 600 may include a platform assembly with linear motion components arranged in an X-Y configuration. The platform may comprise a planar surface mounted on aluminum rails 606 and guides 608 that enable precise two-dimensional movement.

[0127] In some cases, movement subsystem 600 may incorporate a multi-well plate holder 610 positioned in the center of frame structure 602, as shown in FIG. 14A. Multi-well plate holder 610 may be designed to secure a standard laboratory well plate 612, allowing for precise positioning of samples during the analysis process.

[0128] Movement subsystem 600 may also include various electrical components and wiring harnesses to control and power the motion control elements. FIG. 14B and FIG. 14C illustrate an assembled movement subsystem 600 with flexible conduits extending from the sides of the mechanism. These conduits may house electrical or fluid connections necessary for the operation of the subsystem.

[0129] An electrical system 700 of system 10 may include components for power distribution and control connections, as illustrated in FIG. 15. System 10 may receive AC input 702 power which may be converted into multiple DC voltage levels, including 5V, 24V, - 12V/+12V, and 12V 704, for powering various components of the apparatus.

[0130] In one embodiment, electrical system 700 may include an electronics board 706 that may serve as the central control unit. Electronics board 706 may interface with multiple subsystems, including optical components, motion control elements, and environmental control components. Electronics board 706 may be connected to two lasers (laser 1, laser 2) 708, each with dedicated power supplies 710, and two detectors (detector 1, detector 2) 712 for fluorescence measurements.

[0131] Electrical system 700 may incorporate a motion control system comprising motors 714 and pumps 716. In this embodiment, electrical system 700 may include four motors (motor 1, motor 2, motor 3, motor 4), each equipped with a home switch 718, and five pumps (pump 1, pump 2, pump 3, pump 4 and pump 5) 716 for fluid handling. Home switch 718 indicates a sensor that confirms the needle and ejection system are in the correct position to start the sample transfer, ensuring consistent operation. An air solenoid 720 may be included to control pneumatic operations within the apparatus. X/Y and Z solenoids 722, 724 may manage precise positioning operations. Specifically, X/Y solenoid 722 controls the fluidic paths for reagents and samples in the X and Y axes, enabling precise handling and dispensation. Z Solenoid 724 manages vertical movement and dispensation of fluids, crucial for accurate pipetting and liquid handling.

[0132] Environmental control may be maintained through multiple fans 726. In this implementation, electrical system 700 may include four enclosure fans and a positive pressure fan 726. Fans 726 are powered to maintain optimal temperature conditions within system 10, ensuring electronic components do not overheat. This is vital for the reliability and longevity of system 10. Electrical system 700 may also incorporate multiple UV sterilization components for different areas of the apparatus, including area 728, plate 730, biopsy 732, and bottle regions 734 (via a door switch). These UV components may be controlled through a relay system 736.

[0133] Temperature regulation may be achieved through a temperature controller 738 connected to thermoelectric coolers (TECs) 740 and a temperature sensor 742. Here, temperature controller 738 regulates the temperature within critical parts of system 10, ensuring that assays are carried out at optimal conditions for accurate results. This arrangement may allow for precise control of environmental conditions during biopsy analysis. In other words, temperature controller 738 and thermoelectric coolers (TECs) 740 regulate the temperature of critical areas, such as the stage and samples, ensuring assays are conducted under optimal thermal conditions. [0134] In this embodiment, electrical system 700 may include a computer 746 that interfaces with electronics board 706. As shown in FIG. 15, electrical system 700 may include an Ethernet (network) switch 744 for network connectivity. This network connection may allow for data transfer, remote monitoring, or system updates. Computer 746 may also connect to a webcam 748 for visual monitoring of system 10. In some embodiments, webcam 748 is used for real-time monitoring or imaging during the sample handling process, and receives power according to its voltage requirement. Webcam 748 connects directly to computer 746 for data transmission, allowing for visual confirmation of sample placement and processing.

[0135] FIG. 16 and FIG. 17 show a perspective view, and a front view, respectively of a liquid handling subsystem 800 for an automated biopsy analysis system 10, in accordance with one embodiment of the present invention. Liquid handling subsystem 800 comprises a metal baseplate 802 with multiple vertical mounting structures 804 arranged in a row. The mounting structures 804 support several pump assemblies 806 positioned at different heights. The pumps 806 are interconnected by flexible tubing 808 and electrical wiring, with wires visible throughout the assembly. Mounting blocks 810 are positioned at the base of the structure, providing support and stability. A metallic flexible conduit 812 extends from one side of the assembly. The pumps 806 are arranged in a cascading configuration, allowing for sequential fluid handling operations. The entire assembly is mounted on a work surface, with various mounting hardware visible throughout the structure. [0136] In some embodiments, liquid handling subsystem 800 may include a cabinet (not shown) containing power supply units mounted in the upper left portion, featuring ventilated housings for cooling. A circuit board assembly with multiple connections and LED indicators may be visible in the central area. Cooling fans may be positioned throughout the enclosure to maintain appropriate operating temperatures. The electrical control cabinet may include multiple wire harnesses, including both power cables and control cables, connecting the various components. A data acquisition module with network connectivity may be visible in the lower portion of the cabinet. These components may be mounted on a metal backplane that provides structural support and organization for the electrical system.

[0137] FIG. 17 shows an interior perspective view of a movement subsystem 900, showing linear motion components arranged in a parallel configuration. This view illustrates how the guide rails 902 and bearing assemblies 904 may be mounted on a metallic base plate 906, providing a stable foundation for precise movement control. Movement subsystem 900 may be integrated with other components of the automated biopsy testing apparatus to facilitate various operations. For example, the subsystem may work in conjunction with a compressed gas ejection system to eject biopsy samples from biopsy needles. In some cases, movement subsystem 900 may position a biopsy needle holder over a specific well of a multi-well plate, allowing for precise sample deposition using a burst of compressed gas. As specified above, movement subsystem 900 may include a mechanical stage mechanism with multiple axes of motion, including linear actuators and guide rails arranged in an X-Y configuration.

[0138] The movement subsystem may be designed for precise positioning and movement control in multiple directions. This precision may be crucial for ensuring accurate sample placement, liquid handling, and optical measurements throughout the automated biopsy analysis process.

[0139] The automated biopsy analysis system may integrate various subsystems to perform comprehensive sample analysis while maintaining precise environmental control and providing real-time feedback to users.

[0140] In some cases, system 10 may incorporate a temperature control mechanism to maintain biopsy samples at optimal conditions throughout the analysis process. This temperature control system may include thermoelectric coolers and a temperature sensor. Optionally, control system 24 may be configured to monitor the temperature of the biopsy sample using the temperature sensor. The monitored temperature may be compared to a predetermined temperature set point. Based on this comparison, the control system may adjust the thermoelectric coolers to maintain the biopsy sample at the predetermined temperature. This active temperature regulation may help ensure consistent and reliable analysis results by maintaining stable environmental conditions for the samples.

[0141] System 10 may manage data storage to record various types of information generated during the analysis process using control system 24. In some implementations, system 10 may store measured fluorescent signals obtained from optical measurement system 20. System 10 may also record determined metabolic rates calculated from the fluorescent signal data. Associated metadata, such as sample identifiers, analysis timestamps, and environmental conditions, may be stored alongside the measurement data. This comprehensive data management approach may facilitate later review and analysis of results.

[0142] To provide users with visibility into the analysis process, system 10 may coordinate with user interface 84 to display real-time analysis progress and results. In some cases, user interface 84 may be implemented as a touchscreen display integrated into system 10. The touchscreen interface may allow users to input sample information, initiate analysis protocols, and monitor ongoing analyses. User interface 84 may display information such as current sample temperature, analysis phase progress, and preliminary results as they become available. This real-time feedback may enable users to quickly identify any issues and make informed decisions during the analysis process.

[0143] The touchscreen user interface 84 may serve as the primary means of system operation. The users may interact with user interface 84 to perform tasks such as loading samples, selecting analysis protocols, and reviewing results. In some implementations, user interface 84 may provide step-by-step guidance for system setup and sample loading procedures. The touchscreen may also display system status information, such as reagent levels and maintenance reminders. By centralizing system control and information display in a single touchscreen interface, system 10 may provide an intuitive and efficient user experience for conducting automated biopsy analyses.

[0144] The automated biopsy analysis system may incorporate sophisticated software to control and coordinate its various subsystems. This control software may be designed with a modular architecture, allowing for flexibility and ease of updates as the system evolves.

[0145] In some implementations, the software may include a main control module that oversees the operation of all subsystems. The main control module may manage the overall workflow of the biopsy analysis process, from sample input to data output. The main control module may communicate with individual subsystem modules through a standardized interface, enabling seamless integration of different hardware components. [0146] In some implementations, processor 80 in control system 24 may utilize a real-time operating system (RTOS) to ensure precise timing and coordination of critical operations. This RTOS may allow for deterministic scheduling of tasks, which may be essential for maintaining the accuracy and reliability of the analysis process. Processor 80 may employ multi-threading techniques to handle concurrent operations, such as simultaneous control of motion systems and data acquisition from optical sensors.

[0147] In one example, processor 80 may execute software instructions stored in memory 82 to manage the movement subsystem. Here, processor 80 may interpret high-level commands from the main control software and translate them into precise instructions for the stepper motors and actuators. Processor 80 may incorporate advanced algorithms for trajectory planning and vibration suppression, potentially improving the accuracy of sample positioning and reducing mechanical disturbances during sensitive measurements.

[0148] In some implementations, liquid handling subsystem 204 may be controlled by a fluid management module (not shown) stored in memory 82. The fluid management module may coordinate the operation of pumps, valves, and dispensing mechanisms to ensure accurate and timely delivery of reagents and samples. The fluid management module may include calibration routines to maintain dispensing accuracy over time and may implement error detection algorithms to identify issues such as clogs or air bubbles in the fluid lines.

[0149] In some implementations, memory 82 includes an optical measurement module (not shown). The optical measurement module may be responsible for controlling the lasers, detectors, and associated components of the fluorescence measurement system. The optical measurement module may synchronize laser excitation with detector readout, manage filter wheel positions, and process raw signal data. The optical measurement module may incorporate advanced signal processing algorithms to enhance the signal -to-noise ratio of fluorescence measurements and may include self-diagnostic routines to monitor the performance of optical components.

[0150] In some implementations, memory 82 includes a comprehensive data management module (not shown) to handle the acquisition, processing, and storage of experimental data. The comprehensive data management module may implement a database system to organize and index data from multiple experiments, allowing for efficient retrieval and analysis. The comprehensive data management module may support various data export formats to facilitate integration with external analysis tools and may include features for data backup and archiving to ensure long-term data integrity.

[0151] In some implementations, memory 82 includes a calibration and quality control module (not shown). The calibration and quality control module, when executed, maintains system performance over time. The calibration and quality control module may manage automated calibration routines for various subsystems, track calibration status, and alert users when recalibration is necessary. The calibration and quality control module may implement statistical process control techniques to monitor system performance trends and may generate alerts when parameters drift outside of acceptable ranges.

[0152] In some implementations, memory 82 includes a comprehensive error handling and logging module (not shown) to enhance reliability and facilitate troubleshooting. The error handling and logging module may implement a hierarchical error classification system, allowing for appropriate responses to different types of errors. The error handling and logging module may generate detailed log files recording system events and errors, which may be valuable for system maintenance and performance optimization. [0153] In some implementations, memory 82 includes an analysis and reporting module (not shown). The analysis and reporting module, when implemented, to processes raw data and generates meaningful results. The analysis and reporting module may incorporate algorithms for metabolic rate calculations, statistical analysis, and data visualization. The analysis software may support customizable report templates and may include features for automated report generation to streamline the experimental workflow.

[0154] In some implementations, memory 82 includes a simulation module (not shown) to facilitate system testing and operator training. The simulation module may allow for virtual execution of experimental protocols without the need for physical samples or reagents. The simulation module may incorporate models of system behavior to provide realistic feedback and may be used to validate new protocols before implementation on the actual system.

[0155] In some implementations, memory 82 includes an artificial intelligence (Al) module to enhance system performance and data analysis. The Al module may employ machine learning algorithms to optimize system parameters based on historical performance data. The Al module may also assist in data interpretation, potentially identifying patterns or anomalies that may not be apparent through conventional analysis methods.

[0156] In some implementations, memory 82 includes a user interface module (not shown). The user interface module may be implemented to provide an intuitive and responsive interface for system operation. The user interface module, when executed, may generate the graphical elements displayed on the touchscreen interface and handle user inputs. The user interface module, when executed, may implement context-sensitive help features and may include user authentication and access control mechanisms to ensure proper system usage and data security. [0157] Transceiver 88 may enable remote monitoring and control of system 10. Transceiver 88 may implement secure protocols for data transmission and may support features such as remote software updates and diagnostic access. Transceiver 88 may also facilitate integration with laboratory information management systems (LIMS) for seamless data exchange in research or clinical environments.

[0158] Definitions

[0159] In the context of this invention, the following definitions may apply:

[0160] "Biopsy" may refer to a sample of tissue or cells taken from a living organism for examination, typically to diagnose disease or determine metabolic activity.

[0161] "Metabolic rate" may refer to the rate at which an organism uses energy for its life processes, often measured through the consumption of oxygen or production of carbon dioxide. [0162] "Fluorescence" may refer to the emission of light by a substance that has absorbed light or other electromagnetic radiation of a different wavelength.

[0163] "Laser" may refer to a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation.

[0164] "Photodetector" may refer to a sensor that converts light into an electrical signal.

[0165] "Thermoelectric cooler" (TEC) may refer to a solid-state heat pump that transfers heat using the Peltier effect.

[0166] "Peristaltic pump" may refer to a type of positive displacement pump used for pumping a variety of fluids.

[0167] "Solenoid valve" may refer to an electromechanically operated valve controlled by an electric current through a solenoid. [0168] "UV sterilization" may refer to the process of using ultraviolet light to kill or inactivate microorganisms.

[0169] "NADH" may refer to nicotinamide adenine dinucleotide (NAD) + hydrogen (H), a coenzyme found in all living cells that plays a key role in cellular metabolism.

[0170] "DNA" may refer to deoxyribonucleic acid, the molecule that carries genetic instructions in all known living organisms.

[0171] "Assay" may refer to an investigative procedure in laboratory medicine, pharmacology, environmental biology, and molecular biology for qualitatively assessing or quantitatively measuring the presence or amount of a target entity.

[0172] "High-throughput" may refer to methods and systems for rapid screening or analysis of large numbers of samples.

[0173] "In vitro" may refer to studies or experiments conducted using components of an organism that have been isolated from their usual biological surroundings.

[0174] The automated biopsy analysis system may offer several advantages over conventional methods of biopsy analysis. These advantages may stem from the integration of multiple automated processes and advanced technologies within a single system.

[0175] In some cases, the system may incorporate a sterilization system configured to sterilize components using ultraviolet light. This sterilization system may help maintain aseptic conditions throughout the analysis process, potentially reducing the risk of sample contamination. The use of ultraviolet light for sterilization may allow for rapid and effective decontamination of system components without the need for chemical agents.

[0176] The automated biopsy analysis system may include a temperature control system configured to maintain biopsy samples at predetermined temperatures during analysis. This temperature control system may comprise thermoelectric coolers and a temperature sensor. By maintaining precise temperature control, the system may help ensure consistent and reliable analysis results across multiple samples.

[0177] In some implementations, the system may employ a positive pressure environment to prevent contamination. This positive pressure system may help maintain a sterile environment within the biopsy analysis system by preventing the ingress of airborne contaminants. The combination of ultraviolet sterilization and positive pressure may provide a multi-layered approach to maintaining sterility throughout the analysis process.

[0178] The automated nature of the system may reduce the potential for human error in sample handling and analysis. By minimizing manual interventions, the system may help ensure consistent sample preparation and measurement procedures across multiple analyses.

[0179] In some cases, the system may include a software module for data visualization of metabolic activity. This visualization capability may allow researchers or clinicians to more easily interpret complex metabolic data, potentially leading to faster and more accurate insights from biopsy analyses.

[0180] The system may also incorporate statistical analysis tools within its software for in- depth analysis of results. These tools may enable users to perform advanced statistical analyses on the data generated by the system, potentially uncovering subtle trends or relationships that might be difficult to detect through manual analysis.

[0181] The integration of multiple analytical steps within a single automated system may increase the efficiency of biopsy analysis workflows. This increased efficiency may allow for higher throughput in research or clinical settings, potentially reducing the time required to obtain results from biopsy samples. [0182] In some implementations, the automated nature of the system may allow for standardization of biopsy analysis procedures across different laboratories or clinical settings. This standardization may help improve the comparability of results between different research studies or diagnostic procedures.

[0183] The comprehensive data management capabilities of the system may facilitate more robust record-keeping and traceability in biopsy analysis procedures. This improved data management may be particularly beneficial in research settings or in clinical applications where detailed documentation is critical.

[0184] By automating complex analytical procedures, the system may reduce the level of specialized training required for personnel to conduct biopsy analyses. This reduction in training requirements may potentially make advanced biopsy analysis techniques more accessible to a wider range of researchers or clinicians.

[0185] In some cases, the system's ability to maintain precise control over environmental conditions and analytical parameters may lead to improved reproducibility of biopsy analysis results. This enhanced reproducibility may be particularly valuable in research settings or in the development of new diagnostic techniques.

[0186] The automated biopsy analysis system may offer the potential for remote monitoring and control of analysis procedures. This capability may allow for expert oversight of biopsy analyses even when specialists are not physically present at the site of sample processing.

[0187] The automated biopsy analysis system offers advantages in terms of sterility maintenance, temperature control, data analysis and visualization, efficiency, standardization, and reproducibility compared to conventional manual methods of biopsy analysis. These advantages make the system particularly suitable for applications in research, clinical diagnostics, and other fields where high-throughput, reliable biopsy analysis may be required. [0188] A number of implementations have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other implementations are within the scope of the following claims.

[0189] Clause 1. A system for automated biopsy analysis, comprising: a biopsy needle holder configured to secure a biopsy needle; a sample transfer system configured to transfer a biopsy sample from the biopsy needle to a well of a multi-well plate; a liquid handling system configured to add and remove liquids from the well; an optical measurement system configured to measure fluorescent signals from the well; and a control system configured to coordinate operations of the biopsy needle holder, sample transfer system, liquid handling system, and optical measurement system.

[0190] Clause 2. The system of clause 1, wherein the sample transfer system comprises a compressed gas ejection system configured to eject the biopsy sample from the biopsy needle using a burst of compressed gas.

[0191] Clause 3. The system of clause 1, wherein the liquid handling system comprises a plurality of pumps configured to dispense and aspirate liquids to and from the well.

[0192] Clause 4. The system of clause 1, wherein the optical measurement system comprises: a laser configured to excite fluorescent markers in the biopsy sample; and a photodetector configured to detect fluorescent emissions from the excited markers.

[0193] Clause 5. The system of clause 1, further comprising a sterilization system configured to sterilize components of the system using ultraviolet light. [0194] Clause 6. The system of clause 1, further comprising a temperature control system configured to maintain the biopsy sample at a predetermined temperature during analysis.

[0195] Clause 7. The system of clause 6, wherein the temperature control system comprises thermoelectric coolers and a temperature sensor, and wherein the control system is further configured to: monitor a temperature of the biopsy sample using the temperature sensor; compare the monitored temperature to the predetermined temperature; and adjust the thermoelectric coolers to maintain the biopsy sample at the predetermined temperature.

[0196] Clause 8. A method for automated biopsy analysis, comprising: securing a biopsy needle containing a biopsy sample in a biopsy needle holder; transferring the biopsy sample from the biopsy needle to a well of a multi-well plate; adding a liquid to the well containing the biopsy sample; incubating the biopsy sample; measuring a fluorescent signal from the well; and analyzing the measured fluorescent signal to determine a characteristic of the biopsy sample.

[0197] Clause 9. The method of clause 8, wherein transferring the biopsy sample comprises ejecting the sample from the biopsy needle using a burst of compressed gas.

[0198] Clause 10. The method of clause 8, wherein adding the liquid comprises dispensing the liquid using a pump-based liquid handling system.

[0199] Clause 11. The method of clause 8, further comprising sterilizing components of a biopsy analysis system using ultraviolet light prior to securing the biopsy needle.

[0200] Clause 12. The method of clause 8, further comprising maintaining the biopsy sample at a predetermined temperature during incubation using a temperature control system.

[0201] Clause 13. The method of clause 12, wherein maintaining the biopsy sample at the predetermined temperature comprises: monitoring a temperature of the biopsy sample using a temperature sensor; comparing the monitored temperature to the predetermined temperature; and adjusting thermoelectric coolers to maintain the biopsy sample at the predetermined temperature. [0202] Clause 14. The method of clause 13, further comprising: removing the liquid from the well after incubation; adding a fluorescent reagent to the well; exciting the fluorescent reagent using a laser; detecting fluorescent emissions from the excited reagent using a photodetector; analyzing the detected fluorescent emissions to determine a metabolic rate of the biopsy sample; and generating a report indicating the determined metabolic rate.

[0203] Clause 15. A non-transitory computer-readable medium storing instructions that, when executed by a processor, cause the processor to perform operations for automated biopsy analysis, the operations comprising: controlling a biopsy needle holder to secure a biopsy needle; directing a sample transfer system to transfer a biopsy sample from the biopsy needle to a well of a multi-well plate; managing a liquid handling system to add and remove liquids from the well; coordinating an optical measurement system to measure fluorescent signals from the well; and processing the measured fluorescent signals to determine a characteristic of the biopsy sample. [0204] Clause 16. The non-transitory computer-readable medium of clause 15, wherein the operations further comprise: controlling a sterilization system to sterilize components of a biopsy analysis system using ultraviolet light prior to securing the biopsy needle.

[0205] Clause 17. The non-transitory computer-readable medium of clause 15, wherein directing the sample transfer system comprises activating a compressed gas ejection system to eject the biopsy sample from the biopsy needle using a burst of compressed gas.

[0206] Clause 18. The non-transitory computer-readable medium of clause 15, wherein the operations further comprise: controlling a temperature control system to maintain the biopsy sample at a predetermined temperature during analysis. [0207] Clause 19. The non-transitory computer-readable medium of clause 18, wherein controlling the temperature control system comprises: monitoring a temperature of the biopsy sample using a temperature sensor; comparing the monitored temperature to the predetermined temperature; and adjusting thermoelectric coolers to maintain the biopsy sample at the predetermined temperature.

[0208] Clause 20. The non-transitory computer-readable medium of clause 19, wherein the operations further comprise: controlling the liquid handling system to remove a first liquid from the well after incubation and add a fluorescent reagent to the well; coordinating the optical measurement system to excite the fluorescent reagent using a laser and detect fluorescent emissions from the excited reagent using a photodetector; analyzing the detected fluorescent emissions to determine a metabolic rate of the biopsy sample; generating a report indicating the determined metabolic rate; managing data storage to record the measured fluorescent signals, the determined metabolic rate, and associated metadata; controlling a positive pressure system to maintain a sterile environment within the biopsy analysis system; and coordinating a user interface to display real-time analysis progress and results to a user.

Claims

1. A system for automated biopsy analysis, the system comprising: a biopsy needle holder and delivery system configured to secure a biopsy needle; a sample transfer system configured to transfer a biopsy sample from the biopsy needle to a well of a multi-well plate; a liquid handling system configured to dispense and aspirate liquids to and from the well; an optical measurement system configured to measure fluorescent signals emitted from the well; and a control system configured to control operations of the biopsy needle holder and delivery system, the sample transfer system, the liquid handling system, and the optical measurement system.

2. The system of claim 1, wherein the sample transfer system comprises a compressed gas ejection system configured to eject the biopsy sample from the biopsy needle using a burst of compressed gas.

3. The system of claim 1, wherein the liquid handling system comprises a plurality of pumps configured to dispense and aspirate the liquids to and from the well.

4. The system of claim 1, further comprising a sterilization system configured to maintain a sterile environment within the system through ultraviolet light sterilization and positive pressure airflow.

5. The system of claim 1, wherein the optical measurement system comprises: at least one laser configured to excite fluorescent reagents in the biopsy sample; and at least one photodetector configured to detect fluorescent emissions from the excited reagents.

6. The system of claim 1, further comprising a temperature control system configured to maintain the biopsy sample at a predetermined temperature during the automated biopsy analysis.

7. The system of claim 6, wherein the temperature control system comprises thermoelectric coolers and a temperature sensor, and wherein the control system is further configured to: monitor a temperature of the biopsy sample using the temperature sensor; compare the temperature monitored with the predetermined temperature; and adjust the thermoelectric coolers to maintain the biopsy sample at the predetermined temperature.

8. A method for automated biopsy analysis, the method comprising the steps of: securing a biopsy needle containing a biopsy sample in a biopsy needle holder and delivery system; transferring the biopsy sample from the biopsy needle to a well of a multi-well plate; adding a liquid to the well containing the biopsy sample; incubating the biopsy sample; measuring a fluorescent signal from the well; and analyzing the measured fluorescent signal to determine a characteristic of the biopsy sample.

9. The method of claim 8, wherein the step of transferring the biopsy sample comprises ejecting the biopsy sample from the biopsy needle using a burst of compressed gas.

10. The method of claim 8, wherein the step of adding the liquid comprises dispensing the liquid using a pump-based liquid handling system.

11. The method of claim 8, further comprising sterilizing components of a biopsy analysis system using ultraviolet light prior to securing the biopsy needle.

12. The method of claim 8, further comprising maintaining the biopsy sample at a predetermined temperature during incubation using a temperature control system.

13. The method of claim 12, wherein maintaining the biopsy sample at the predetermined temperature comprises: monitoring a temperature of the biopsy sample using a temperature sensor; comparing the monitored temperature to the predetermined temperature; and adjusting thermoelectric coolers to maintain the biopsy sample at the predetermined temperature.

14. The method of claim 13, further comprising: removing the liquid from the well after incubation; adding a fluorescent reagent to the well; exciting the fluorescent reagent using a laser; detecting fluorescent emissions from the excited reagent using a photodetector; analyzing the detected fluorescent emissions to determine a metabolic rate of the biopsy sample; and generating a report indicating the metabolic rate determined.

15. A non-transitory computer-readable medium storing instructions that, when executed by a processor, cause the processor to perform operations for automated biopsy analysis, the operations comprising: controlling a biopsy needle holder and delivery system to secure a biopsy needle; directing a sample transfer system to transfer a biopsy sample from the biopsy needle to a well of a multi-well plate; managing a liquid handling system to dispense and aspirate liquids to and from the well of the multi-well plate; coordinating an optical measurement system to measure fluorescent signals from the well; and processing the measured fluorescent signals to determine a characteristic of the biopsy sample.

16. The non-transitory computer-readable medium of claim 15, wherein the operations further comprise: controlling a sterilization system to sterilize components of a biopsy analysis system using ultraviolet light prior to securing the biopsy needle.

17. The non-transitory computer-readable medium of claim 15, wherein directing the sample transfer system comprises activating a compressed gas ejection system to eject the biopsy sample from the biopsy needle using a burst of compressed gas.

18. The non-transitory computer-readable medium of claim 15, wherein the operations further comprise: controlling a temperature control system to maintain the biopsy sample at a predetermined temperature during analysis.

19. The non-transitory computer-readable medium of claim 18, wherein controlling the temperature control system comprises: monitoring a temperature of the biopsy sample using a temperature sensor; comparing the monitored temperature to the predetermined temperature; and adjusting thermoelectric coolers to maintain the biopsy sample at the predetermined temperature.

20. The non-transitory computer-readable medium of claim 19, wherein the operations further comprise: controlling the liquid handling system to remove a first liquid from the well after incubation and add a fluorescent reagent to the well; coordinating the optical measurement system to excite the fluorescent reagent using a laser and detect fluorescent emissions from the excited reagent using a photodetector; analyzing the detected fluorescent emissions to determine a metabolic rate of the biopsy sample; generating a report indicating the determined metabolic rate; managing data storage to record the detected fluorescent emissions, the determined metabolic rate, and associated metadata; controlling a positive pressure system to maintain a sterile environment within the biopsy analysis system; and coordinating a user interface to display real-time analysis progress and results to a user.