Automated pipetting system for pathogen isolation

Abstract

The current invention involves a method of isolating a pathogen from a food sample using an automated pipetting system to remove supernatant from centrifuge tubes down to a calibrated volume. The automated pipetting system includes an automated pipetting system with the capacity to determine the calibrated volume to prevent disturbing a biological mass at the bottom of the centrifuge tubes.

Description

ATTORNEY DOCKET NO. : PTRK-009 / 00WQAUTOMATED PIPETTING SYSTEM FOR PATHOGEN ISOLATIONSTATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0001] This invention was made with government support under SBIR 2127054 awarded by the National Science Foundation. The government has certain rights in the invention.TECHNICAL FIELD

[0002] The disclosures herein relate generally food safety and systems related thereto. In particular, the disclosures herein relate to systems, devices and methods for an automated pipetting system for the removal of supernatant from and isolation of pathogen within microcentrifuge tubes.BACKGROUND

[0003] In the field of food processing, ensuring the safety and quality of food products is of paramount importance. The spread of foodborne illnesses may be prevented through careful monitoring of food by producers and sellers, and detection of foodborne microbes present in food processing lots. Many protocols related to food safety involve pathogen isolation by centrifugation of centrifuge tubes, allowing supernatant to be removed off of a solid sample or the separation of immiscible liquids of different densities. To this end, many labs use centrifugation of centrifuge tubes as a step in manually removing a supernatant from a biological mass.

[0004] However, the process of removing the supernatant manually leaves a user prone to error. Various robotic technologies exist to provide an automated approach, but these methods are often costly, require complex installation and operation, and can take up a significant amount of space. There is a critical need for smaller and lower cost systems of automated pipetting for pathogen isolation in food safety testing.BRIEF SUMMARY

[0005] The present disclosure relates to a system for automated pipetting, comprising a frame, comprising a tube mount, a plunger action arm, a pipette mount, and an actuator subsystem comprising a first actuator and second actuator, the first actuator configured to control translation of the pipette mount, and the second actuator configured to control translation of the plunger action arm, a sensor subsystem, and a processing subsystem.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ

[0006] According to embodiments, the present disclosure relates to a system for automated pipetting, comprising a frame, comprising a tube mount, a plunger action arm, a pipette mount, and a tube mount, and an actuator subsystem comprising a first actuator and second actuator, the first actuator configured to control translation of the tube mount, and the second actuator configured to control translation of the plunger action arm, a sensor subsystem, and a processing subsystem.

[0007] According to embodiments, the present disclosure further relates to a tube rack, comprising a planar material having a plurality of apertures therethrough, the plurality of apertures being sized to receive a tube, and an alignment feature disposed on the planar material proximal each of the plurality of apertures to orient the tube received therein.

[0008] According to embodiments, the present disclosure further related to a method for detecting pathogens in a food sample, comprising, obtaining a food sample suspected of comprising at least one pathogen, processing the food sample to generate a liquid food sample solution, isolating a biological mass from a filtrate of the liquid food sample solution, and detecting a presence of the at least one pathogen within the biological mass via a biological assay.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The accompanying figures, which are incorporated herein and form a part of the specification, illustrate some, but not the only or exclusive, example embodiments and / or features. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than limiting.

[0010] FIGs. 1A-1D are illustrative flowchart representations of a method of isolating a pathogen from a food sample, according to variations herein. FIG. 1A is a system level overview. FIG. IB is an illustrative flowchart representation of a method of isolating a pathogen. FIG. 1C an illustrative flowchart representation of a method of retrieving a retentate. FIG. ID is an illustrative flowchart representation of a method of isolating a pathogen from the retentate.

[0011] FIGs. 2A and 2B are schematics of an automated pipetting system for use with a pipette, according to variations herein.

[0012] FIGs. 3A and 3B are illustrative flowchart representations of a method of operating a pipetting system to remove supernatant.

[0013] FIG. 4 is an illustrative flowchart representation of a method of obtaining and processing sensor data, according to variations herein.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ

[0014] FIG. 5 is an illustrative flowchart representation of a method of controlling the translation of the position of the pipette, according to variations herein.

[0015] FIG. 6 is an illustrative flowchart representation of a method of controlling the retraction of the plunger, according to variations herein.

[0016] FIGs. 7A-7C depicts a perspective (FIG. 7A), frontal (Fig. 7B), and side (FIG. 7C) view of an automated pipetting system for a pipette, according to variations herein.

[0017] FIG. 8 depicts a perspective view of a pipette mount, according to variations herein.

[0018] FIGs. 9A-9C depict a perspective (FIGs. 9A-9B) and frontal (FIG. 9C) view of a tube holder, according to variations herein.

[0019] FIGs. 10A-10F depict a frontal view of a tube rack (FIG. 10A) and perspective views of the tube rack seated within a centrifuge (FIG. 10B) and tube holder (FIGs. 10C-10F), according to variations herein.

[0020] FIGs. 11A-11H depict views of paired tube racks (FIG. 11A-C), a view of a tube rack (FIG. HD), a view of a tube rack with tubes seated therein (FIG. HE), views of the paired tube racks with tubes seated therein (FIGs. 11F-G), and a view of a tube rack seated within a tube holder (FIG. 11H), according to variations herein.

[0021] FIGs. 12A-12B depict views of an alternative system for supernatant extraction, according to embodiments herein.DETAILED DESCRIPTION

[0022] All publications, patents and patent applications, including any drawings and appendices, are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0023] The following description includes information that may be useful in understanding the present disclosure. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed disclosures, or that any publication specifically or implicitly referenced is prior art.Definitions

[0024] The term “a” or “an” refers to one or more of that entity, i.e. can refer to plural referents. As such, the terms “a,” “an,” “one or more,” and “at least one” are used interchangeably herein. In addition, reference to “an element” by the indefinite article “a” or “an” does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there is one and only one of the elements.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ

[0025] Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device or the method being employed to determine the value, or the variation that exists among the samples being measured. Unless otherwise stated or otherwise evident from the context, the term “about” means within 10% above or below the reported numerical value (except where such number would exceed 100% of a possible value or go below 0%). When used in conjunction with a range or series of values, the term “about” applies to the endpoints of the range or each of the values enumerated in the series, unless otherwise indicated. As used in this application, the terms “about” and “approximately” are used as equivalents.Method of Detecting a Pathogen in a Food Sample

[0026] Described herein are systems, devices, and methods of isolating and detecting a pathogen from a food sample, an exemplary, high-level illustration of which is shown in Fig. 1 A. As shown in Fig. 1 A, a method of isolating and detecting a pathogen, referred to as method A, includes a combination of methods Al, A2, and A3, which are performed chronologically from the farm to the laboratory. In brief, the method A described herein, which will be described in more detail below, involves obtaining a raw food sample at method Al, isolating a pathogen from the raw food sample at method A2, and detecting the pathogen, if present, within the isolate at method A3.

[0027] Specifically, at method Al of method A, a raw food sample can be obtained. In embodiments, the raw food sample can be derived from a source food or, generally, from a farming operation. In embodiments, the source food comprises fruits, vegetables, sprouts, grains, protein, diary, fats, and oils. In embodiments, the protein comprises poultry, beef, pork, fish, and eggs. In embodiments, the food source comprises poultry. In embodiments, the raw food sample can be prepared for pathogen isolation prior to method A2. In embodiments, preparation for pathogen isolation comprises standard laboratory processing techniques of a biological sample. In embodiments, the processing techniques of a biological sample can comprise homogenization and cell lysis. In embodiments the raw food sample can undergo processing comprising spinning, mixing, cutting, stomaching, emulsifying, blending, grinding, and mincing. At method A2 of method A, a pathogen can be isolated from the processed food sample. This method will be discussed in further detail below, however, in brief, the raw food sample can be submerged and / or incubated within an enrichment medium, the resulting medium can be filtered, a retentate can be recovered from the filter, the retentate can be centrifuged, and a pathogen can be isolated by an automated pipetting process (describedATTORNEY DOCKET NO. : PTRK-009 / 00WQ herein) which isolates the pathogen. Subsequently, at method A3 of method A, the isolated pathogen can be resuspended, processed, and detected. In embodiments, the isolated pathogen can be detected and, optionally, identified, with a biological assay. In embodiments, the biological assay comprises at least one of a culture-based technique, immunoassay, PCR, biomarker, biosensor, and DNA microarray. In embodiments, the biological assay comprises PCR. In embodiments, the food sample comprises at least one pathogen. In embodiments, the at least one pathogen comprises bacteria, viruses, parasites, fungi, and protozoa. In embodiments, the at least one pathogen comprises Salmonella, Escherichia coli, Listeria monocytogenes, Campylobacter, Clostridium perfringens, Vibrio, Staphylococcus aureus, Norovirus, Hepatitis A virus, Giardia, Cryptosporidium, Toxoplasma gondii, and Trichinella. In embodiments, the biological assay corresponds to the suspected at least one pathogen to be detected.

[0028] Turning now with particular focus to method A2, described herein is a method of isolating a pathogen from a food sample, an exemplary illustration of which is shown in method A2 of Fig. IB.

[0029] At step 101 of method A2, a food sample can be placed into an enrichment medium, which may effectively be an extraction medium, so that particles and organisms on and within the food sample can be put into solution. The food sample and the enrichment medium can be incubated before processing in a system of the present disclosure. An exemplary protocol may include placing the food sample in a bag with an enrichment medium and incubating the bag and its contents. In embodiments, the food sample is not incubated.

[0030] At subprocess 105 of method A2, a retentate can be retrieved. An exemplary protocol of retrieving the retentate may include attaching a filter to the “enrichment” bag and filtering the food sample and the enrichment medium, thus retrieving that which is retained in or on the filter during a filtration or separation process. Subprocess 105 will be described in further detail with reference to Fig. 1C.

[0031] At subprocess 110 of method A2, a pathogen can then be isolated from the retrieved retentate. Retentate isolation will be described in greater detail with reference to, for example, Fig. ID.

[0032] Turning now to Fig. 1C, a method of retrieving a retentate will be described with reference to the exemplary illustration of subprocess 105 of Fig. 1C. At step 106 of subprocess 105, a filter is removed from the bag containing the food sample and the enrichment medium after filtration has been performed. Fluid is then backwashed through the filter at step 107 toATTORNEY DOCKET NO. : PTRK-009 / 00WQ recover the retentate. In subprocess 110, a pathogen is then isolated from the recovered retentate, as will be described further with reference to Fig. ID.

[0033] At step 111 of subprocess 110, the retentate can be allocated, or aliquoted, into at least one tube. In embodiments, the at least one tube comprises a plurality of tubes. In embodiments, the at least one tube comprises centrifuge tubes. In embodiments, the plurality of tubes comprises tubes of the same size. In embodiments, the plurality of tubes comprises tubes of different size. In embodiments, the centrifuge tubes can range in size from about 1 mL (e.g., microcentrifuge tubes) to about 50 mL (e.g., 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mL, including any values or ranges therein).

[0034] At optional step 112 of method 110, the at least one tube can be placed into a tube rack. The tube rack will be described in further detail below with reference to Figs. 10A-10C and 11 A-l 1H. In embodiments, the tube rack comprises a material, which may be planar, having a plurality of apertures therethrough, the plurality of apertures being sized to receive a tube, and at least one alignment feature disposed on the planar material proximal each of the plurality of apertures to orient the tube received therein. In embodiments, the tube rack comprises a plurality of ring-like structures having apertures therethrough, the plurality of ring-like structures being connected sequentially by a flexible connector, which may permit the tube rack to be flexed in at least one axis. The tube rack may further comprise at least one alignment feature proximate each ring-like structure. The at least one alignment feature ensures all the tubes seated in the tube rack face a desired orientation or direction. By facing the tubes in the desired orientation or direction, they can be more easily uncapped and recapped throughout the method. In embodiments, the alignment feature comprises locating pins, bushings, dowels, centerlines, reference marks, fixtures, linear guides, rails, magnetic clamps, magnetic bases, and alignment algorithms. In embodiments, the tube rack can hold a number of tubes comprising 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more tubes, including any values or ranges therein. In embodiments, the tube rack holds centrifuge tubes. In embodiments, the centrifuge tubes can range in size from about 1 mL to about 50 mL (e.g., 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mL, including any values or ranges therein).

[0035] At step 113 of method 110, the tubes are centrifuged to form a pelleted biological mass therein. In embodiments, the pelleted biological mass is located at the bottom of the tube(s) after centrifugation. In embodiments, a supernatant is present in the tube(s) above the pelleted biological mass. In embodiments, the pelleted biological mass comprises cells, subcellular components, proteins, nucleic acids, viral particles, and metabolites. In embodiments, aboutATTORNEY DOCKET NO. : PTRK-009 / 00WQ the same volume of supernatant is present in the tube(s). In embodiments, a different volume of supernatant is present in the tube(s).

[0036] At step 114 of method 110, the tubes centrifuged tubes are seated within a tube holder. The tube holder will be described in more detail below with reference to Figs. 7A-9C, and 10C- 10F. In brief, the tube holder can hold 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10 or more tube(s), including any ranges or values therein. In embodiments, the tube holder can receive the tube(s) seated in the tube rack. In embodiments, the tube holder can hold tubes of different sizes. In embodiments, the tube holder holds centrifuge tube(s). In embodiments, the centrifuge tubes can range in size from about 1 mL (e.g., a microcentrifuge tube) to about 50 mL (e.g., 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mL, including any values or ranges therein).

[0037] At subprocess 115 of method 110, the tube holder can be positioned within an automated pipetting system and the automated pipetting system can be operated to remove supernatant from the tube(s) seated in the tube holder. Subprocess 115 is described in more detail below with reference to Figs. 3-8. In brief, subprocess 115 involves an automated pipetting system for retrieving a supernatant while leaving the pelleted biological mass, or a desired volume of supernatatnt, at the bottom of the tube(s) undisturbed.

[0038] Described herein are various ways to operate the automated pipetting system at subprocess 115. In embodiments, the metrics of the automated pipetting system can be preconfigured before the system is initiated. In embodiments, the volume of supernatant to be removed from centrifuge tubes can be preconfigured (or, inversely, the volume of the supernatant to be left in the centrifuge tube can be defined). For example, when the centrifuge tube is 1.5 mL, the pipetting system can operate in an automated way to control various features - for example, actuators and pipettes can be controlled to ensure that a desired volume of supernatant is removed from the centrifuge tubes. These features can include, for instance, removing supernatant from the 1.5 mL centrifuge tube down to specified volumes from about 1 pL to about 100 pL (e.g., 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 pL, including any values or ranges therein.) The features can include removing supernatant from the 1.5 mL centrifuge tube down to specified volumes of 5 pL or 10 pL.

[0039] In embodiments, the preconfigured metrics further comprise manufacturer of tube, size of tube, volume of tube, volume of sample in tube, biological mass, and rate of translation for the pipette and plunger. In embodiments, the automated pipetting system self-adjusts these preconfigured metrics as it proceeds. In embodiments, the preconfigured metrics of the automated pipetting system can be adjusted manually. In embodiments, the preconfiguredATTORNEY DOCKET NO. : PTRK-009 / 00WQ metrics of the automated pipetting system can be remotely adjusted. The exemplary automated pipetting system described in System 200 of Fig. 2B can automate various features based on a set of criteria described in detail below.Automated Pipetting System and Methods Thereof i. System

[0040] Described herein are systems, devices and methods for operating an automated pipetting system, an exemplary schematic of which is shown in Fig. 2A. As shown in Fig. 2A, the automated pipetting system, referred to as system 200, can be used to remove supernatant from one or more tubes comprising a pelleted biological mass, and involves an automated pipetting system that can accommodate a pipette. In embodiments, the pipette comprises a singular or multichannel pipette.

[0041] Generally, the system 200 may comprise a frame 219, a processing subsystem 231, and a sensor subsystem 232. In embodiments, the frame 219 further comprises a tube mount 220, an actuator subsystem 221, a pipette plunger action arm 226, a pipette mount 227, and buttons 225. The actuator subsystem 221 comprises one or more actuators. In embodiments, the actuator subsystem 221 comprises actuator #1 222 and at least one of actuator #2 223 and actuator #3 224. Within the frame 219, actuator #1 222 is configured to move the pipette plunger action arm 226. When present, actuator #2223 is configured to move the pipette mount 227. When present, actuator #3 224 is configured to move the tube mount 220. In embodiments, one or both of actuator #2 223 and actuator #3 224 can be included within the actuator subsystem 221. The actuator subsystem 221 can be coupled to a rail of frame 219 with a length that defines an axis of travel. Each of the individual actuators within the actuator subsystem 221 can then move their corresponding structures along the axis of travel. For example, actuator #1 222 can move the pipette plunger action arm 226 up or down the axis of travel based on a set of instructions. Accordingly, the pipette plunger action arm 226 can engage a plunger of a pipette to modify a partial vacuum generated therein.

[0042] As introduced above, in embodiments, actuator #3 224 is configured to move the tube mount. In embodiments, actuator #3 224 moves the tube mount 220 along a rail of frame 219. In embodiments, actuator #3 224 moves the tube mount 220 upward along the axis of travel towards the pipette mount 227. In embodiments, actuator #3 224 moves the tube mount 220 upwards along the axis of travel, while actuator #2 moves the pipette mount 227 down along an axis of travel.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ

[0043] In embodiments, the processing subsystem 231 can interact with the frame 219 and the sensor subsystem 232 can interact with the processing subsystem 231. The sensor subsystem 232 can comprise at least one sensor (e.g., sensor #1 233, sensor #2 234). The processing subsystem and sensor subsystem are described in more detail below.

[0044] Returning to Fig. 2 A, the tube mount 220 of frame 219 of system 200 can be couplable to a tube holder 229, which may be introduced to the system 200 during an automated pipetting operation. The tube holder 229 may be further couplable to a tube rack 230. In embodiments, a pipette 228 can be coupled to the pipette mount 227 of frame 219, and also moved along the axis of travel by the actuator subsystem 221. For example, actuator #2 223 may actuates the pipette mount 227 and the pipette 228 coupled thereto can also move along the axis of travel. The movement of the pipette plunger action arm 226 can occur in tandem with the pipette mount 227. Moreover, movement of the tube mount 220 via actuator #3 224 may also occur concurrently. The actuator subsystem is controlled by a process described later on. The buttons 225 can be located along the frame 219 and may activate or direct the system 200.

[0045] The tube rack 230 can also be used independently of the system 200. For instance, tubes can be placed in the tube rack 230 and then centrifuged. The tube rack 230 can maintain the alignment of the tubes during centrifugation and improve handling when moving the plurality of tubes to and from the centrifugation unit. it. Structure

[0046] Described below are the mechanical and physical properties of the various components illustrated in Fig. 2A in further detail.

[0047] In embodiments, the frame 219 of the system 200 comprises a substantially rectangular shape, and a length that defines an axis of travel by a pipette. In embodiments, the frame 219 comprises at least one rail. In embodiments, the rail comprises linear rails, guide rails, linear actuator rails, cartesian rails, sliding rails, track rails, precision rails, mounting rails, and support rails. In embodiments, the frame 219 is made of a material comprising one or more of a metal, polymer, ceramic, and composite.

[0048] In embodiments, the frame 219 can be further coupled to a base. In embodiments, the frame 219 is coupled to a base by a method comprising one or more of a press-fit, a snap-fit, a magnet, a fastener, a screw, a rotational coupling, an adhesive, and welding. In embodiments, the base is a housing that comprises one or more of the sensor subsystem 232 and the actuator subsystem 221. In embodiments, the base comprises a control panel for controlling a pipetting operation. In embodiments, the control panel comprises at least one of a button, a dial, a touch screen, a switch, a slider, a trackpad and a wheel. In embodiments, the base comprises a powerATTORNEY DOCKET NO. : PTRK-009 / 00WQ source selected from at least one of a battery, electrical cord, and solar power. In embodiments, the base further comprises the processing subsystem 231.

[0049] In embodiments, the tube mount 220 can be coupled to the frame by way of the actuator subsystem 220. For example, actuator #3 224 of the actuator subsystem 221 is configured to move the tube mount 220 along an axis of travel on the frame 219. In this example, the tube mount can be further coupled to a tube holder 229, which will also move when the tube mount 220 is actuated. In embodiments, the tube mount 220 can advance up or down the axis of travel. In embodiments, the tube mount 220 can advance towards the pipette mount 227. In embodiments, the tube mount 220 is made of a material comprising one or more of a metal, polymer, ceramic, and composite.

[0050] In embodiments, the tube holder 229 is coupled to the frame 219 via the tube mount 220. In embodiments, the tube holder 229 is coupled to the tube mount 221 via a method comprising one or more of a press-fit, a snap-fit, a magnet, a fastener, a screw, a rotational coupling, an adhesive, and welding.

[0051] In embodiments, the tube mount 221 further comprises a lever, as shown in Figs. 9A- 9C, to cap and uncap a plurality of tubes. In embodiments, the tube mount 221 further comprises an axis on which the lever rotates. In embodiments, the lever can cap and uncap the plurality of tubes all at once. In embodiments, the lever is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber. In embodiments, the lever is made of metal. In embodiments, the tube holder 229 is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber.

[0052] In embodiments, the tube holder 229 may further comprise the tube rack 230 of Fig. 2A. In embodiments, the tube rack 229 is mounted to the tube holder 229. In embodiments, the tube holder 229 comprises two arms for mounting to the tube mount 220. In embodiments, as will be described with respected to Figs. 11 A-l 1H, the tube rack 230 comprises a plurality of apertures which are designed to accept a plurality of tubes. In embodiments, the tube rack 230 can be adjusted to fit tubes of different sizes. In embodiments, tube rack 230 has grasping features. In embodiments, the tube rack 230 is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber. In embodiments, the tube rack 230 is not free standing. In embodiments, the tube rack 230 is free standing. In embodiments, the tube rack 230 is flexible. In embodiments, the tube rack 230 can have a design printed on a surface. In embodiments, each hole in the tube rack 230 can comprise a label. In embodiments, the label comprises an alphanumeric label and / or a symbol. InATTORNEY DOCKET NO. : PTRK-009 / 00WQ embodiments, the tube rack 230 further comprises a spot for a removable label. In embodiments, the tube rack 230 comprises at least one alignment feature. In embodiments, the tube rack 230 comprises at least one tab for grasping the tube rack 230. In embodiments, the at least one tab is located on an end of the tube rack 230. In embodiments, the at least one tab is located on one end of the tube rack 229.

[0053] In embodiments, the actuator subsystem 221 can be coupled to the frame 219. In the above example, the actuator subsystem 221 comprises actuator #1 223 and at least one additional actuator. The at least one additional actuator may be one or more of actuator #2 223 and actuator #3 224. The actuator subsystem 221 can be coupled to at least one rail of the frame 219. In embodiments, the actuator subsystem is coupled to the at least one rail of the frame 219 via a method comprising one or more of a press-fit, a snap-fit, a magnet, a fastener, a screw, a rotational coupling, an adhesive, and welding. In embodiments the actuator subsystem 222 comprises at least one of a linear actuator, a rotary actuator, a hydraulic actuator, an electronic actuator, and a thermal actuator. In embodiments, the actuator subsystem 222 comprises at least one of a linear slide, belt drive, screw drive, pneumatic cylinder, hydraulic cylinder, and magnetic drive. In embodiments, each actuator of the actuator subsystem 222 comprises a motor comprising at least one of at least one of a DC motor, AC motor, stepper motor, servo motor, universal motor, linear motor, hydraulic motor, and pneumatic motor.

[0054] In embodiments, the frame 219 further comprises buttons 225. In embodiments, the buttons 225 comprise a start and stop button. In embodiments, the buttons comprise at least one, at least two, at least three, at least four or at least five volume buttons. In embodiments, the buttons comprise at least two volume buttons. In embodiments, the volume buttons range from about 0.1 pL to about 10,000 pL (e.g., 0.1, 1, 25, 50, 75, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1,000, 1,500, 2,000, 2,500, 3,000, 3,500, 4,000, 4,500, 5,000, 5,500, 6,000, 6,500, 7,000, 7,500, 8,000, 8,500, 9,000, 9,500, or 10,000 pL, including any values or ranges therein). In embodiments, the buttons 225 comprise two volume buttons. In embodiments, the volume buttons comprise a 20 pL and a 50 pL button. In embodiments, the buttons 225 further comprise one or more of a push button, toggle button, rocker button, rotary button, membrane button, capacitive button, touch button, emergency button, mute button, reset button, control button, volume button, and power button. In embodiments, the buttons 225 indicate how much supernatant to leave in the centrifuge tubes. In embodiments, the buttons 225 signal how much supernatant to remove from the centrifuge tubes. In embodiments, the buttons 225 correspond to the size of the tubes and the amount of supernatant typically present therein.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ

[0055] In embodiments, the automated pipetting system depicted in Fig. 2A can be used with an exterior pipette 228. The pipette 228 can be coupled to and removed from the frame 219 by way of the pipette mount 227. In embodiments, the pipette 228 is mounted to the pipette mount 227 via a method comprising one or more of a press-fit, a snap-fit, a magnet, a fastener, a screw, a rotational coupling, an adhesive, and welding. In embodiments, the pipette 228 is coupled to the pipette mount 227 by way of a magnet. In embodiments, the pipette 228 is a multichannel pipette or a single channel pipette. In embodiments, the pipette 228 is a multichannel pipette.

[0056] In embodiments, the pipette mount 228 can be coupled to at least one rail of the frame 219. In embodiments, the pipette mount 228 is coupled to the at least one rail of the frame via a method comprising one or more of a press-fit, a snap-fit, a magnet, a fastener, a screw, a rotational coupling, an adhesive, and welding. In embodiments, the pipette mount has a substantially square shape.

[0057] Moreover, the exemplary system 200 involves an exterior processing subsystem 231 and sensor subsystem 232. These will be described below in more detail.Hi. Processing circuitry

[0058] With reference to FIG. 2B, a processing subsystem will now be described in more detail and with context to a generalized workflow of the automated pipetting system 200.

[0059] As shown in FIG. 2B, the processing subsystem 231 comprises a controller 270. In embodiments, the controller 270. comprises one or more of a processor 271, a communication device 272, a memory 273, an input device 274, and, optionally, a display 275, which may be communicatively coupled to the controller 320. The display 275 is dashed in FIG. 2B to indicate that it may be local to an enclosure of the automated pipetting system 200 or may be located remotely.

[0060] In variations, the processor 271 of the controller 270 described herein may process data and / or other signals to control one or more components of the frame 219. The processor 271 may be configured to receive, process, compile, compute, store, access, read, write, and / or transmit data and / or other signals. Additionally, or alternatively, the processor 271 may be configured to control one or more components of a device (e.g., console, touchscreen, personal computer, laptop, tablet, server).

[0061] In some variations, the processor 271 may be configured to access or receive data and / or other signals from one or more sensors of the sensor subsystem 232, the frame 219, a server, a controller 270, and a storage medium (e.g., memory, flash drive, memory card, database). In some variations, the processor 271 may be any suitable processing device configured to run and / or execute a set of instructions or code and may include one or more data processors, imageATTORNEY DOCKET NO. : PTRK-009 / 00WQ processors, graphics processing units (GPU), physics processing units, digital signal processors (DSP), analog signal processors, mixed-signal processors, machine learning processors, deep learning processors, finite state machines (FSM), compression processors (e.g., data compression to reduce data rate and / or memory requirements), encryption processors (e.g., for secure wireless data transfer), and / or central processing units (CPU). The processor 271 may be, for example, a general-purpose processor, Field Programmable Gate Array (FPGA), an Application Specific Integrated Circuit (ASIC), a processor board, and / or the like. The processor 271 may be configured to run and / or execute application processes and / or other modules, processes and / or functions associated with the processing subsystem 231, the frame 219 or the sensor subsystem 232.

[0062] The systems, devices, and / or methods described herein, such as those that will be described with reference to Figs. 3-6, may be performed by software (executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, a general- purpose processor (or microprocessor or microcontroller), a field programmable gate array (FPGA), and / or an application specific integrated circuit (ASIC). Software modules (executed on hardware) may be expressed in a variety of software languages (e.g., computer code), including structured text, typescript, C, C++, C#, Java®, Python, Ruby, Visual Basic®, and / or other object-oriented, procedural, or other programming language and development tools. Examples of computer code include, but are not limited to, micro-code or micro-instructions, machine instructions, such as produced by a compiler, code used to produce a web service, and files containing higher-level instructions that are executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encrypted code, and compressed code.

[0063] In some variations, the memory 272 of the controller 270 may be configured to store data and / or information. In some embodiments, the memory 273 may include one or more of a random-access memory (RAM), static RAM (SRAM), dynamic RAM (DRAM), a memory buffer, an erasable programmable read-only memory (EPROM), an electrically erasable readonly memory (EEPROM), a read-only memory (ROM), flash memory, volatile memory, nonvolatile memory, combinations thereof, and the like. In some embodiments, the memory 273 may store instructions to cause the processor 271 to execute modules, processes, and / or functions associated with the device, such as image processing, image display, sensor data, data and / or signal transmission, data and / or signal reception, and / or communication. Some embodiments described herein may relate to a computer storage product with a non-transitory computer-readable medium (also may be referred to as a non-transitory processor-readableATTORNEY DOCKET NO. : PTRK-009 / 00WQ medium) having instructions or computer code thereon for performing various computer- implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not include transitory propagating signals per se (e.g., a propagating electromagnetic wave carrying information on a transmission medium such as space or a cable). The computer code (also may be referred to as code or algorithm) may be those designed and constructed for the specific purpose or purposes. In some embodiments, the memory 273 may be configured to store any received data and / or data generated by the controller 270 and / or the cell processing system. In some embodiments, the memory 273 may be configured to store data temporarily or permanently.

[0064] In some variations, the input device 274 of the controller 270 may comprise or be coupled to a display 275. Input device 274 may be any suitable device that is capable of receiving input from a user, for example, a keyboard, buttons, touch screen, etc. For example, the display 275, which may include the input device 274, may provide the user with possible assay orders to be executed. The user may then select which assay order should be executed first and may also provide additional instructions before the automated analysis is initiated. As will be described later, this user input may provide grouping information for orchestrating the assay workflow. The input device 274 may include at least one switch configured to generate a user input. For example, an input device 274 may include a touch surface for a user to provide input (e.g., finger contact to the touch surface) corresponding to a user input. An input device 274 including a touch surface may be configured to detect contact and movement on the touch surface using any of a plurality of touch sensitivity technologies including capacitive, resistive, infrared, optical imaging, dispersive signal, acoustic pulse recognition, and surface acoustic wave technologies. In embodiments of an input device 274 including at least one switch, a switch may have, for example, at least one of a button (e.g., hard key, soft key), touch surface, keyboard, analog stick (e.g., joystick), directional pad, mouse, trackball, j og dial, step switch, rocker switch, pointer device (e.g., stylus), motion sensor, image sensor, and microphone. A motion sensor may receive user movement data from an optical sensor and classify a user gesture as a user input. A microphone may receive audio data and recognize a user voice as a user input. The input device 274 and / or the display 275 may be located within an enclosure of the processing subsystem or may be located remotely at, e.g., a computer workstation.

[0065] Image data may be output on the display 275. In some variations, the display 275 may include at least one of a light emitting diode (LED), liquid crystal display (LCD), electroluminescent display (ELD), plasma display panel (PDP), thin film transistor (TFT),ATTORNEY DOCKET NO. : PTRK-009 / 00WQ organic light emitting diodes (OLED), electronic paper / e-ink display, laser display, and / or holographic display.

[0066] In some variations, the display 275 may be configured to display a graphical user interface (GUI). The GUI may be configured for designing an automated pipetting workflow and monitoring a volume of supernatant in a centrifuge tube(s) through the automated pipetting workflow in real time. For example, the GUI may be a automated pipetting workflow design home page. The GUI may indicate that no automated pipetting workflows have been selected or loaded. A create icon (e.g., “Create a Process”) may be selectable for a user to begin an automated pipetting workflow design process.

[0067] In some variations, the system 200 may optionally include one or more output devices in addition to the display 275, such as, for example, an audio device and haptic device. An audio device may audibly output any system data, alarms, and / or notifications. For example, the audio device may output an audible alarm when a malfunction is detected. In some variations, an audio device may include at least one of a speaker, a piezoelectric audio device, a magnetostrictive speaker, and / or a digital speaker. In some embodiments, a user may communicate with other users using the audio device and a communication channel. For example, a user may form an audio communication channel (e.g., VoIP call).

[0068] In some variations, the communication device 272 of the controller 270 may be configured to communicate with another controller and one or more databases. The communication device 272 may be configured to connect the controller 270 to another system (e.g., Internet, remote server, database) by wired or wireless connection. In some variations, the system 200 may be in communication with other devices via one or more wired and / or wireless networks. In some embodiments, the communication device 272 may include a radiofrequency receiver, transmitter, and / or optical (e.g., infrared) receiver and transmitter configured to communicate with one or more devices and / or networks. The communication device 272 may communicate by wires and / or wirelessly. Moreover, the communication device 272 can comprise a link between the frame and processing circuitry. For example, the frame and processing circuitry can comprise two different locations, and therefore a communication link can be implemented to connect the two elements.

[0069] Described herein are processing and sensor subsystems for controlling the automated pipetting system, illustrated in FIG. 2 A in further detail. These exemplary methods are further described in Figs. 3A and 3B, which include a preset automated configuration and a dynamic automated configuration, respectively.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ

[0070] As shown in Fig. 3 A, the exemplary method 315A can be used to preconfigure the automated pipetting system based on a small set of preset parameters. In embodiments, the preset parameters can comprise a manufacturer of a tube, volume of a tube, volume of a sample in a tube, and expected grams of a biological mass. In embodiments, the preset parameters can further comprise a variety of properties of a supernatant and / or a biological mass. In embodiments, the properties can further comprise viscosity of a supernatant, density of a biological mass, hardness of a biological mass, tensile strength of a biological mass, and / or elasticity of a biological mass. In embodiments, the preset parameters can further comprise a length and width of a tube and a length and width of a biological mass. In embodiments, the preset parameters are entered into an interface that interacts with the processing subsystem described herein. In embodiments, the preset parameters can be controlled by buttons located on the frame. In embodiments, the preset parameters can be configured before, during, or after the pipette is mounted in dashed step 316A. In embodiments, the preset parameters can be configured before, during, or after the tube holder is mounted in dashed step 317A.

[0071] At step 318A of method 315A, a plunger of a pipette is depressed to actuate a plunger action arm to move the plunger into the pipette. Actuation of the plunger action arm, which includes depression and retraction of the plunger, corresponds to movement of actuator #1. The actuation and subsequent depression of the plunger action arm can be controlled by the processing circuitry. Depression and retraction of the plunger modifies a partial vacuum applied within the pipette, and within each pipette tip attached thereto. Depression of the plunger action arm, for instance, generates a partial pressure within the pipette and within each pipette tip attached thereto so that the pipette is prepared to remove supernatant from the tube(s).

[0072] At step 355A of method 315A, the automated pipetting system receives the user input regarding the test sample. In embodiments, the user input comprises at least one of the preset parameters described above. The processing subsystem can then process the user input and provide a response. The preset parameters can be received through the use of buttons on the frame. For example, the buttons can indicate volumes of supernatant to leave in the tube or volumes of the tubes themselves.

[0073] At step 356A of method 315 A, the automating pipetting system performs the removal of the supernatant based on the user input received in step 355A. To this end, the plunger action arm and one or more of the pipette mount and the tube mount can be actuated to submerge the pipette tips in the supernatant and to extract, based on a user input regarding a desired extraction volume, supernatant without disrupting the biological mass. In this exemplary method theATTORNEY DOCKET NO. : PTRK-009 / 00WQ pipette can be retracted once a certain criterion is met based on the preset parameters. For example, when a user indicates the tubes used have a preset volume, that setting can then indicate to the automated pipetting system the volume of supernatant to collect. For instance, a user can indicate they are using a 1.5 pL centrifuge tube, and based on that preset parameter, the automated pipetting system can stop collecting supernatant at a particular volume that is less than the volume of the centrifuge tube and such that the biological mass is undisturbed.

[0074] Fig. 3B demonstrates a dynamic method of controlling the automated pipetting system. As shown in Fig. 3B, the exemplary method 315B can be used to control the translation of one or more of a pipette and a tube mount and retraction of a plunger and involves a processing circuitry and at least one sensor that interacts with the automated pipetting system described above. The exemplary method 315B illustrated in Fig. 3B can be performed with a pipette and tube holder previously mounted to a frame of the automated pipetting system. For instance, a pipette can be mounted to the frame of the automated pipetting system at step 316B of method 315B, and a tube holder can be mounted to the tube mount of the frame of the automated pipetting system at step 317B of method 315B. As will be described below, a processing circuitry of a processing subsystem, which may include a computer, can be configured to generate signals and execute instructions corresponding to steps 318B, subprocesses 335B, 340B, and 350B, and step 360B of method 315B.

[0075] At step 318B of method 315B, a plunger of a pipette is depressed to actuate a plunger action arm to move the plunger into the pipette. Actuation of the plunger action arm, which includes depression and retraction of the plunger, corresponds to movement of actuator #1. The actuation and subsequent depression of the plunger action arm can be controlled by the processing circuitry. Depression and retraction of the plunger modifies a partial vacuum applied within the pipette, and within each pipette tip attached thereto. Depression of the plunger action arm, for instance, generates a partial pressure within the pipette and within each pipette tip attached thereto so that the pipette is prepared to remove supernatant from the tube(s).

[0076] Next, a control algorithm CA that performs data processing and actuation of the actuator subsystem is initialized. The control algorithm CA includes, at subprocess 335B of method 315B, receiving and processing sensor data from one or more sensors of the system. The processed data, which includes absolute and / or relative positions of features of the system, can then be used by each of subprocess 350B and subprocess 340B to control translation of the plunger and at least one of the pipette and tube mount, respectively.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ

[0077] As stated, subprocess 340B of method 315B provides a method of controlling the translation of at least one of the pipette and the tube mount. This method can be controlled by the processing circuitry described above. The translation of the pipette and / or the tube mount, which corresponds to translation of the pipette mount via actuator #2 and / or translation of the tube mount via actuator #3, can be up or down along the axis of travel along the frame of the automated pipetting system. As stated, subprocess 350B of method 315B provides a method of controlling the retraction of the plunger. In embodiments, subprocesses 340B, 350B are executed concurrently. In embodiments, the control algorithm CA can be iteratively performed. In embodiments, the control algorithm is iteratively performed until a desired amount of a supernatant is removed from a respective tube. In an example, the desired amount of the supernatant may leave only a pelleted biological mass in the respective tube. In embodiments, the control algorithm CA is performed iteratively until a set of criteria, that relate both to individual control of the pipette and the plunger, as well general criteria related to supernatant extraction, are satisfied. As will be described below, these criteria include, as representative examples, a relative position of a pipette tip and a respective air-liquid interface of the supernatant within a respective tube and a relative position of the pipette tip and at least a portion of the pelleted biological mass within the respective tube. In embodiments, each of these criterion is evaluated based on sensor data received from the sensor subsystem and processed by the processing subsystem at subprocess 335B.

[0078] With reference to method 435 of Fig. 4, sub process 335B of method 315B will be described, whereby an exemplary sensor subsystem monitors and processes the status of various components of the automated pipetting system.

[0079] First, at step 436 of method 435, sensor data is received from at least one sensor of the sensor subsystem. In embodiments, the at least one sensor subsystem comprises at least two, at least three, at least four, or at least five sensors. In embodiments, the at least one sensor of the sensor subsystem comprises at least one camera. In embodiments, the at least one sensor of the sensor subsystem comprises at least one of a visible light sensor, ultrasound sensor, image sensor, infrared sensor, temperature sensor, proximity sensor, pressure sensor, touch sensor, color sensor, flow sensor, level sensor, digital sensor, analog sensor, and a force sensor. In embodiments, the at least one sensor comprises a visible light sensor, an image sensor, or an infrared sensor. In embodiments, the sensor captures a binary image of a plurality of tubes. In embodiments, the at least one sensor captures an image of a plurality of tubes and the image is subsequently converted to a binary image. In embodiments, the at least one sensor comprises a camera that acquires a picture of the plurality of tubes.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ

[0080] In embodiments, the at least one sensor comprises at least one visible light sensor. An exemplary visible light sensor detects and measures light in a visible spectrum and converts the visible by way of a photodetector into an electrical signal that can be processed. In embodiments, a photodetector comprises at least one of a photodiode, phototransistor, and light dependent resistor. In this method an undesired wavelength of light can be filtered out with an optical filter, while the electrical signal generated by the photodetector can be enhanced with an amplification circuit. In embodiments, the sensor subsystem further comprises at least one camera. In embodiments, the at least one camera can be coupled to the automated pipetting system. In embodiments, the at least one camera can be separate from the automated pipetting system.

[0081] In embodiments, the sensor comprises at least one image sensor. An exemplary image sensor captures and processes visual information in a form comprising images or video. The image sensor can convert light from a captured image or video into a signal. For example, a charged-coupled device can convert the image into an analog signal, and a complementary metal-oxide-semiconductor can convert the image into an electrical signal. Moreover, this example process uses a lens to focus light onto an image sensor and then uses a filter enhance of isolate certain wavelengths of light. In embodiments, the at least one camera can be coupled to the automated pipetting system. In embodiments, the at least one camera can be separate from the automated pipetting system.

[0082] In embodiments, the sensor comprises at least one infrared sensor. An exemplary infrared sensor detects infrared radiation which is part of the electromagnetic spectrum with wavelengths longer than visible light from about 700 nm to about 1 mm. The infrared radiation can be converted into an electrical signal by way of an infrared detector. An infrared detect can include but is not limited to a photodiode, pyroelectric detector and a thermopile. An optical filter can be used to select a specific infrared wavelength and a lens can be used to focus the infrared radiation onto the detector. An amplification circuit can then be used to enhance the signal and a processing circuitry can then analyze the signal at step 437 of method 435 to identify relevant information.

[0083] At step 437 of method 435, the sensor data received at step 436 can be processed to identify, for at least one tube, absolute and / or relative positions of features of the system. For instance, the sensor data can be processed to identify an absolute position of each respective pipette tip, an absolute position of a respective air-liquid interface, and an absolute position of a respective biological mass. In embodiments, the absolute position of a respective biological mass can be an absolute position of an uppermost region of the respective biological mass. ForATTORNEY DOCKET NO. : PTRK-009 / 00WQ example, the sensor data can be processed to determine that the bottom of a respective pipette tip (or an average of a plurality of pipette tips) is at a position of 80 mm in the y-direction, while an uppermost position of a respective biological mass (or an average of an uppermost position of a plurality of respective biological masses) is at a position of 20 mm in the y- direction. In another instance, the sensor data can be processed to identify positions of each respective pipette tip relative to a position of a respective air-liquid interface. For example, the sensor data can be processed to determine that the bottom of a respective pipette tip (or an average of a plurality of pipette tips) is at a position, in the y-direction, that is + 40 mm above a position of a respective air-liquid interface (or an average of a plurality of air-liquid interfaces). In another instance, the sensor data can be processed to identify relative positions of each respective pipette tip, a respective air-liquid interface, and a respective biological mass. For example, the sensor data can be processed to determine that the bottom of a respective pipette tip (or an average of a plurality of pipette tips) is at a position, in the y-direction, that is - 1 mm below a position of a respective air-liquid interface (or an average of a plurality of airliquid interfaces) and + 5 mm above a position of a respective biological mass (or an average of a plurality of biological masses).

[0084] In embodiments, the sensor subsystem comprises at least one imaging sensor and processing the data comprises applying image processing techniques to an image generated by the at least one imaging sensor. To this end, the processing circuitry can be trained to identify the relevant features of the system and to determine their absolute and / or relative positions within space.

[0085] In embodiments, the absolute and / or relative positions of the relevant features of the system dictate actuation within the actuator subsystem. In particular, actuator #1 and at least one of actuator #2 and actuator #3 can be actuated according to signals from the processing circuitry to actuate the plunger action arm, the pipette mount, and / or the tube mount, respectively, based on the determined absolute and / or relative positions. To this end, actuation of the pipette mount, the tube mount, and the plunger action arm will be described with reference to method 540 of Fig. 5 and method 650 of Fig. 6, respectively. Actuation of the pipette mount, the tube mount, and plunger action arm can be controlled by the processing circuitry described herein.

[0086] First, at Fig. 5, controlling the translation of the pipette via the pipette mount and / or the tube mount is described with reference to method 540.

[0087] Dashed steps 538 and 539 of method 540 indicate that the processing circuitry has determined the absolute and / or relative positions of the relevant features of the automatedATTORNEY DOCKET NO. : PTRK-009 / 00WQ pipetting system. For instance, data has been received related to the determined relative positions of the respective pipette tip(s) and the respective air-liquid interface(s) and the determined relative positions of the respective pipette tip(s), air-liquid interface(s), and / or uppermost end of the respective biological mass(es).

[0088] At step 542 of method 540, the relative positions acquired at steps 538 and 539 are evaluated to determine whether respective criterion are satisfied. For instance, the relative position of a bottom of a respective pipette tip (or an average of a plurality of pipette tips) and a respective air-liquid interface (or an average of a plurality of air-liquid interfaces) is evaluated in view of a respective criterion, which stipulates that the relative position of these features must be no less than a desired value. Defining the criterion in this way allows for stipulation of a position of each pipette tip relative to, e.g., a respective air-liquid interface.

[0089] In embodiments, the respective criterion includes at least two criterion. In embodiments, a first criterion stipulates that a position of a pipette tip should be about 1 mm to about 20 mm (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 mm, including any values or ranges therein) below a position of a respective air-liquid interface, or at a -1 mm to about a - 20 mm position relative to the respective air-liquid interface. In embodiments, the first criterion stipulates that a position of a pipette tip should be about 2 mm below a position of a respective air-liquid interface, or at a - 2 mm position relative to the position of the respective air-liquid interface. In embodiments, a second criterion stipulates that a position of a pipette tip and an uppermost end of a respective biological mass should be greater than about 1 mm to about 20 mm (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 mm, including any values or ranges therein), or at a + 1 mm to about a + 20 mm position relative to the respective biological mass. In embodiments, the respective criterion includes a third criterion which stipulates that a position an air-liquid interface and an uppermost end of a respective biological mass should be greater than about 0.5 mm to about 5 mm (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 mm, including any values or ranges therein), or at a + 0.5 mm to about a + 5 mm position relative to the respective biological mass.

[0090] In embodiments, controlling signals are generated based on the evaluations at step 542 of method 540. For instance, at step 543 of method 540, a signal to advance the pipette mount and / or the tube mount can be generated when the evaluation concludes that a relative position of the pipette tip and the air-liquid interface is greater than a -2 mm position and a relative position of the pipette tip and the biological mass is greater than a + 0.5 mm position. When these criteria are satisfied, the pipette is advanced toward the tube holder via the pipette mount and / or the tube mount is advanced toward the pipette via actuator #3. When the evaluationATTORNEY DOCKET NO. : PTRK-009 / 00WQ concludes, at step 544 of method 540, that one or more of these criterion is not satisfied, a signal to halt the pipette and / or the tube mount can be generated. In embodiments, method 540 includes an optional step 545 that includes generation of a signal to the plunger action arm to similarly stop translation (e.g., retraction). This signal serves as a safety and is intended to prevent the aspiration of any part of the biological mass.

[0091] Similar to method 540, method 650 of Fig. 6 relates to controlling the retraction of the plunger. As in method 540, the automated pipetting system can receive the determined relative positions of system features at dashed steps 638 and 639.

[0092] Optionally, a plunger action arm stop signal generated at step 545 of method 540 may also be received before beginning method 650 at step 642. When a stop signal is received at step 645 of method 650, method 650 proceeds directly to step 653 and translation of the plunger action arm is halted.

[0093] In the absence of a stop signal, the relative positions acquired at steps 638 and 639 are evaluated at step 642 of method 650 to determine whether respective criterion are satisfied. For instance, the relative position of a bottom of a respective pipette tip (or an average of a plurality of pipette tips) and a respective air-liquid interface (or an average of a plurality of air-liquid interfaces) is evaluated in view of a respective criterion, which stipulates that the relative position of these features must be no less than a desired value but no more than a desired value in order to actuate the plunger action arm. Defining the criterion in this way allows for stipulation of a position of each pipette tip relative to, e.g., a respective air-liquid interface.

[0094] In embodiments, the respective criterion includes at least two criterion. In embodiments, a first criterion stipulates that a position of a pipette tip should be about 0.5 mm to about 3 mm (0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, and 3, including any values or ranges therein) below a position of a respective air-liquid interface, or at a -1 mm to about a - 3 mm position relative to the respective air-liquid interface. In embodiments, the first criterion stipulates that a position of a pipette tip should be about 2 mm below a position of a respective air-liquid interface, or at a - 2 mm position relative to the position of the respective air-liquid interface in order to permit retraction of the plunger action arm. In embodiments, a second criterion stipulates that a position of a pipette tip and an uppermost end of a respective biological mass should be greater than about 1 mm to about 20 mm (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 mm, including any values or ranges therein), or at a + 1 mm to about a + 20 mm position relative to the respective biological mass in order to permit retraction of the plunger action arm. In embodiments, the respective criterion includes a third criterion which stipulates that a position an air-liquid interface and an uppermost end of aATTORNEY DOCKET NO. : PTRK-009 / 00WQ respective biological mass should be greater than about 0.5 mm to about 5 mm (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 mm, including any values or ranges therein), or at a + 0.5 mm to about a + 5 mm position relative to the respective biological mass in order to permit retraction of the plunger action arm.

[0095] When the criterion is satisfied the rate of translation of the actuated components of the automated pipetting system can be modified. The rate of translation can be preset as in method 315A of Fig. 3A or can be adjusted during the method of 315B of Fig. 3B.

[0096] In embodiments, controlling signals are generated based on the evaluations at step 642 of method 650. For instance, at step 652 of method 650, a signal to retract the plunger action arm can be generated when the evaluation concludes that a relative position of the pipette tip and the air-liquid interface is between a - 0.25 mm position and a - 2 mm position and a relative position of the pipette tip and the biological mass is greater than a + 0.5 mm position. When these criteria are satisfied, the plunger is retracted via the plunger action arm. When the evaluation concludes, at step 653 of method 650, that one or more of these criterion is not satisfied, a signal to halt the pipette can be generated.

[0097] After the CA executed, method 315B of Fig. 3B concludes at step 360B after method 540 and 650 are completed (i.e., translation of their respective components is ceased). Thus, at step 360, the pipette is retracted, and a resulting isolated biological mass proceeds to method A3 for additional processing and pathogen detection. After the pipette is retracted, the supernatant collected in the pipette tips can be discarded and the pelleted biological mass that remains in the tubes can be resuspended in preparation for a biological assay performed in A3.Uses in Medicine and Research i. Medical & Food Processing

[0098] Described herein is a method for detecting pathogens in a food sample, comprising obtaining a food sample suspected of comprising at least one pathogen, processing the food sample to make a liquid food solution, isolating a supernatant from a filtrate of the liquid food solution, and detecting a presence of the at least one pathogen within the supernatant via a biological assay. In embodiments, the automated pipetting system described herein can be used for diagnostic purposes. In embodiments, the diagnostic purposes comprise detecting a pathogen responsible for an outbreak. In embodiments, the outbreak may be a result of one or more events comprising contaminated food products, improper food handling, contaminated water supply, food processing manufacturing issues, foodbome toxins, contaminatedATTORNEY DOCKET NO. : PTRK-009 / 00WQ ingredients, food handler practices, improper food packaging, temperature abuse, improper thawing, and inadequate sanitization.

[0099] In embodiments, the automated pipetting system can be used in surveillance for foodbome illness. In embodiments, the automated pipetting system can be used in prevention of outbreaks. In embodiments, the system can be implemented in surveillance systems comprising national, local and regional surveillance.

[0100] The systems described herein may help to reduce the time required for sample processing, enabling quicker analysis of food samples and expedited identification of potential pathogens. In embodiments, the automated pipetting system described herein would reduce the time it takes to process a sample compared to a standard manual approach by at least about 1- fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-folder, or 10-fold, including any ranges or values therein. In embodiments, the time to process a sample is reduced by at least about 1 minute, 5 minutes, 10 minutes, 15 minute, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 or 24 hours including any ranges or values therein. In embodiments, the sample comprises a food sample. In embodiments, the automated pipetting system described herein would reduce the time it takes to analyze a food sample compared to a manual approach by at least about 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-folder, or 10-fold, including any ranges or values therein. In embodiments, the time to analyze a food sample is reduced by at least about 1 minute, 5 minutes, 10 minutes, 15 minute, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 or 24 hours including any ranges or values therein.

[0101] Additionally, swift detection of pathogens may allow for timely intervention and implementation of appropriate measures to prevent contaminated food from reaching consumers, minimizing the risk of foodborne outbreaks. In embodiments, the automated pipetting system described herein would reduce the time for detecting a pathogen compared to a manual approach by at least about 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-folder, or 10-fold, including any ranges or values therein. In embodiments, the time to detect a pathogen is reduced by at least about 1 minute, 5 minutes, 10 minutes, 15 minute, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 or 24 hours including any ranges or values therein.

[0102] More accessible automated pipetting systems may contribute to improved productivity in food processing facilities. In embodiments, productivity is improved by at least about 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-folder, or 10-fold, including any ranges or values therein. By reducing the pathogen isolation time, the overall throughput of samplesATTORNEY DOCKET NO. : PTRK-009 / 00WQ may be increased, leading to higher production volumes without compromising quality assurance. This increased productivity may translate into better supply chain management, reduced costs, and enhanced customer satisfaction. ii. Research

[0103] Centrifugation to retrieve a pelleted biological mass is common in many scientific laboratory procedures. In embodiments, the laboratory procedures comprise cell pelleting, protein precipitation, DNA / RNA extraction, plasma separation, cell fractionation, microbial harvesting, and sample purification. The systems, devices and methods described herein could also be used in many other scientific laboratory procedures.

[0104] In embodiments, the automated pipetting system described herein would reduce the time it takes to remove a supernatant from a tube(s) compared to a manual approach by at least about 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-folder, or 10-fold, including any ranges or values therein. In embodiments, the time to remove a supernatant from a tube would be reduced by at least about 1 minute, 5 minutes, 10 minutes, 15 minute, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, or 24 hours including any ranges or values therein.

[0105] In embodiments, the automated pipetting system comprises several customizable components. In embodiments, the customizable components comprise tube size, tube number, pipette, tube rack size, tube holder size, pipette tips, sensors, and the rate at which the process occurs.Hi. Exemplary use of system

[0106] An exemplary automated pipetting system set up is illustrated in Figs. 7A-7C. As shown, a pipette 728 can be mounted to a frame 719 of the automated pipetting system described herein by a pipette mount 727. In this example the pipette 728 is a multichannel pipette with pipette tips 746 attached. In embodiments, the pipette tips 726 are attached before mounting the pipette 728 to the frame 719. The pipette 728 can be mounted above a tube holder 729 comprising a plurality of tubes. The tube holder 729 can be mounted to the frame 719 by way of a tube mount 720. The pipette 728 can be mounted to the frame 719 below the pipette plunger action arm 726 via the pipette mount 727. The pipette 728 and pipette plunger action arm 726 can interact. In embodiments, the pipette 728 and pipette plunger action arm 726 can act together. In embodiments, the pipette 728, the pipette plunger action arm 726, and the tube mount 720 can act together. In embodiments, the pipette 728 and pipette plunger action arm 726 can act separately. In embodiments, the pipette 728, the pipette plunger action arm 726, and the tube mount 720 can act separately. In embodiments, the pipette 728, the pipette plungerATTORNEY DOCKET NO. : PTRK-009 / 00WQ action arm 726, and / or the tube mount 720 can be moved by actuators of an actuator subsystem. In embodiments, the actuator subsystem is controlled by a processing subsystem receiving a signal from a sensor subsystem. In embodiments, the buttons 725 are preconfigured to control the volume of supernatant remaining in centrifuge tubes seated in the tube holder 729. In embodiments, the buttons 725 comprise volume settings of 20 pL and 50 pL. In embodiments, a user could activate the automated pipetting system by pressing one or more of the buttons 725. In embodiments, the automated pipetting system is activated after the pipette 728 is mounted. In embodiments, the automated pipetting system is activated while the pipette 728 is mounted. In embodiments, the automated pipetting system is activated before the pipette 728 is mounted. In embodiments, a user could direct the automated pipetting system by pressing one or more of the buttons 725.

[0107] Fig. 8 describes an exemplary user interaction with a pipette 828 and automated pipetting system. As shown in the image of Fig. 8, the user is mounting the pipette 828 to a frame 819 by way of a pipette mount 827. In this example the pipette 828 is coupled to the pipette mount 827 by way of a magnet. The pipette 828 can have pipette tips 846 attached before being mounted. In embodiments, the pipette 828 is mounted to the frame 819 above the tube holder 829. The tube holder is mounted to the frame 819 by way of a tube mount 820. The frame 819 further comprises buttons 825. In embodiments, the buttons 825 can activate or direct the automated pipetting system. In embodiments, the buttons 825 comprise volume buttons. In, embodiments, the volume buttons determine the amount of supernatant remaining in the tubes seated in the tube holder 829. In embodiments, the buttons 825 can be used to activate or direct the automated pipetting system before mounting the pipette 828. In embodiments, the buttons 825 can be used to activate or direct the automated pipetting system while mounting the pipette 828. In embodiments, the buttons 825 can be used to activate or direct the automated pipetting system after mounting the pipette 828.

[0108] Figs. 9A-9C describe an exemplary user interaction with a tube holder 929. As shown in Fig. 9A, the tube holder 929 is mounted to a frame 919 by a tube mount 920. A plurality of tubes can be seated in the tube holder 929. In embodiments, each of the tubes is aligned in the tube holder 929 via a tube rack. In embodiments, the tubes are aligned before placing them in the tube holder 929. In embodiments, the tubes are aligned while placing them in the tube holder 929. In embodiments, the tubes seated in the tube holder 929 are capped. In embodiments, the tubes are capped before being seated in the tube holder 929. The tube mount 920 can further comprise a lever 986 and an axis 987such that the lever 986 can rotate on the axis 987. Alternatively, the lever 986 can be coupled to the tube holder 929. The tubes may beATTORNEY DOCKET NO. : PTRK-009 / 00WQ seated within the tube mount 920 via the tube holder 929 such that the lever 986 is operatively engaged with a cap of each of the tubes. The lever 986 can be raised as in Fig. 9B by an actuator subsystem coupled to the frame 919. In embodiments, the lever 986 can be raised along an axis 987 manually. When the lever 986 is raised it can lift the caps of the tubes seated in the tube holder 929. In embodiments, the tube caps are lifted concurrently. As shown in Fig. 9C, after the tube caps are lifted in the tube holder 929, the pipette tips 946 can be lowered into the tubes seated in the tube holder 929 (or, conversely, the tube mount 920 can be raised to the pipette tips). In embodiments, the pipette 928 may be lowered, or the tube mount 920 may be raised, such that the pipette tips 946 are below the air-liquid interface of the tubes. At leaset a portion of the supernatant can be removed from the tubes via the pipette tips 946 by way of retraction of the pipette 928. Translation of the pipette 928 and / or the tube mount 920 and retraction of the plunger can be activated once a set of criteria are met. The set of criteria can be determined by a processing subsystem (not shown) receiving a signal from a sensor subsystem (not shown). For example, once the pipette tips 946 are below the air-liquid interface by about 2mm and the above the uppermost end of a biological mass by about 1mm in the tubes the pipette 928 can retract and remove supernatant from the tubes.

[0109] Figs. 10A-11H depict a tube rack 1030 of the present disclosure, including uses thereof during centrifugation and automated pipetting tasks such as those described herein.

[0110] Figs. 10A-10F, for instance, describe an exemplary user interaction with a tube rack 1030. As shown in Fig. 10A, centrifuge tubes 1081 are seated in the tube rack 1030. The tube rack 1030 can hold at least one tube. In embodiments, the tube rack 1030 aligns the tubes 1081 in the same direction. To this end, the tube rack 1030 may comprise at least one alignment feature proximate each of the apertures therethrough to align the tubes 1081. In embodiments, the tubes 1081 in the tube rack 1030 are capped. As in Fig. 10B, the tube rack 1030 can then be placed in a centrifuge. Utilizing a tube rack 1030 provides a convenient and efficient way to transfer tubes to the centrifuge and from the centrifuge to their next task (such as the automated pipetting system of the present disclosure). As shown in Fig. 10A, the tube rack 1030 comprises a plurality of apertures corresponding to a plurality of tubes seated therein. The tube rack 1030 is made from a flexible material (e.g., silicone rubber) that permits multi-axial movement when placed in the centrifuge, as shown in Fig. 10B. The tube rack 1030 further comprises grasping features 1081 to permit ease of maneuverability of the tube rack 1030 between laboratory workstations. This process can enable all tubes in the tube rack 1030 to remain aligned in the same direction. In addition to aiding in placement within a centrifuge, asATTORNEY DOCKET NO. : PTRK-009 / 00WQ in Fig. 10B, this alignment also enables easy placement of the tube rack 1030 into a tube holder 1029, as in Fig. 10C. Grasping features 1081 also aid in this positioning. In embodiments, the tube rack 1030 allows for the tubes to be transferred to a variety of equipment while maintaining the same orientation and grouping. In embodiments, the equipment comprises centrifuges and heat-blocks.[OHl] In Fig. 10D, the tube holder 1029 comprising the tube rack 1030 can be coupled to a tube mount 1020 of the automated pipetting system described herein. The tube mount 1020 can be coupled to the frame 1019. The tubes in the tube rack 1030 and tube holder 1029 can be aligned and capped before being coupled with the tube mount 1020. As shown in Fig. 10E a lever 1086 coupled to the tube mount 1020 can be raised to open all the caps of the tubes in the tube holder 1029 and tube rack 1030. The pipette tips 1046 can be positioned directly above the open tubes seated in the tube holder 1029 and tube rack 1030. As shown in Fig. 10F the tube rack 1030 has an alignment feature that can keep the tubes aligned in the tube holder 1029.

[0112] Figs. 11 A-l 1H provide an additional embodiment of a tube rack, according to aspects of the present disclosure. Fig. 11D depicts a tube rack 1130, according to embodiments. The tube rack 1130 comprises a plurality of ring-like structures 1188. The plurality of ring-like structures 1188 may be arranged and sequentially connected by flexible members 1183. Each respective flexible connector 1183 permits the plurality of ring-like structures 1188 to flex in at least one axis, and preferably in at least two or three axes. Each of the plurality of ring-like structures 1188 forms an aperture 1184 therethrough. Each respective aperture 1184 may be sized to receive a centrifuge tube 1185, as shown in Fig. HE. In embodiments, the tube rack 1130 comprises at least one grasping feature 1181. Each of the ring-like structures 1188 may further comprise at least one alignment feature, as better shown in Figs. 11 A-l 1C. As shown in Figs. 11 A-l 1C, the tube rack 1130 may further comprise at least one alignment feature 1182 proximate each ring-like structure 1188. For instance, as shown in Figs. 11 A-l 1C, the at least one alignment feature 1182 may be two alignment features configured to position the cap of each tube in a particular direction. The alignment features may comprise locating pins, bushings, dowels, centerlines, reference marks, fixtures, linear guides, rails, magnetic clamps, magnetic bases, and alignment algorithms. In this way, the tubes can be easily positioned within a centrifuge and within a tube holder 1129, as shown in Fig. 11H, for interaction with the automated pipetting system described herein. Each of Figs. 11 A-l 1C depict paired tube racks, each featuring four ring-like structures configured to receive a corresponding centrifuge tube, as shown in Figs. 11F-11H. However, it should be appreciated that the number of ring-likeATTORNEY DOCKET NO. : PTRK-009 / 00WQ structures within a tube rack, and the ability to use one or more tube racks together, is nonlimiting.

[0113] In embodiments, the grasping feature, which may be a tab and the like, comprises indicia to indicate an orientation or a directional side of the tube rack. In embodiments, the tube rack is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber. In embodiments, the plurality of ring-like structures comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, or at least twelve ring-like structures. In embodiments, tube rack has grasping features. In embodiments, the tube rack is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber.

[0114] Referring now to Figs. 12A-12B, an alternative pipetting system will be described. Similar to the above, the pipetting system of Fig. 12A, which is deployed in the corresponding method of Fig. 12B, features a pipette mount 1227, a tube mount 1220, and a tube holder 1229. The pipette mount 1227 is translatable relative to the tube mount 1220 but is generally positioned in proximity to the tube mount 1220. The tube holder 1229 may be fitted within the tube mount 1220, similar to that described above. In use, and after the holder 1229, comprising a plurality of tubes, is positioned with the tube mount 1220, a pipette can be positioned within the claws of the pipette mount 1229 and manually actuated by a user to retrieve supernatant from each of the plurality of tubes within the tube holder 1229. In particular, as described in Fig. 12B, a pipette may be first retrieved at step 1. At step 2, the plunger of the pipette may be manually depressed. At step 3, and while maintaining the depression of the plunger of the pipette, the pipette may be inserted into the pipette mount 1227. As the pipette is moved into the pipette mount 1227 at step 4.1, 4.2, and 4.3, care is taken such that the pipette tips affixed to the pipette do not become substantially submerged (if submerged at all) within the supernatant. At step 5, the pipette is allowed to rest within the pipette mount 1227 prior to retraction of the plunger at step 6, thus initiating removal of supernatant from the plurality of tubes within the tube holder within the tube mount 1220. After completing supernatant extraction at step 7, the pipette may be removed from the pipette mount 1227 at step 8 and the sample within each of the plurality of tubes may be used during further processing.ATTORNEY DOCKET NO. : PTRK-009 / 00WQINCORPORATION BY REFERENCE

[0115] All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entireties for all purposes. However, mention of any reference, article, publication, patent, patent publication, and patent application cited herein is not, and should not be taken as an acknowledgment or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world.

Claims

ATTORNEY DOCKET NO. : PTRK-009 / 00WQCLAIMS1. A system for automated pipetting, comprising: a frame, comprising: a tube mount; a plunger action arm; a pipette mount; and an actuator subsystem comprising a first actuator and second actuator, the first actuator configured to control translation of the pipette mount, and the second actuator configured to control translation of the plunger action arm; a sensor subsystem; and a processing subsystem.

2. The system of claim 1, wherein the pipette mount comprises a magnetic surface for magnetically engaging a pipette.

3. The system of claim 2, wherein the pipette is a single-channel pipette or a multichannel pipette.

4. The system of claim 1, wherein the tube mount is configured to receive a tube holder comprising at least one centrifuge tube therein.

5. The system of claim 4, wherein the at least one centrifuge tube is fitted within a tube rack configured to be received by the tube holder.

6. The system of claim 5, wherein the tube rack comprises one or more apertures configured to receive the at least one centrifuge tube.

7. The system of claim 6, wherein the tube rack further comprises at least one alignment feature proximal to a respective aperture of the one or more apertures to orient the at least one centrifuge tube within the tube rack.

8. The system of claim 7, wherein the at least one alignment feature comprises one or more of locating pins, bushings, dowels, centerlines, reference marks, fixtures, linear guides, rails, magnetic clamps, magnetic bases, and alignment algorithms.ATTORNEY DOCKET NO. : PTRK-009 / 00WO9. The system of claim 1, wherein the actuator subsystem further comprises a third actuator configured to control translation of the tube mount.

10. The system of claim 1, wherein the frame further comprises one or more buttons actuatable to control operation of the system.

11. The system of claim 10, wherein the one or more buttons includes at least one button associated with a predetermined size of a respective centrifuge tube and / or a predetermined volume of supernatant remaining in the respective centrifuge tube after extraction.

12. The system of claim 1, wherein the sensor subsystem comprises one or more visible light sensors.

13. The system of claim 1, wherein the sensor subsystem comprises one or more of a visible light sensor, ultrasound sensor, image sensor, infrared sensor, temperature sensor, proximity sensor, pressure sensor, touch sensor, color sensor, flow sensor, level sensor, digital sensor, analog sensor, and a force sensor.

14. The system of claim 1, wherein the processing subsystem comprises a processing circuitry configured to: receive sensor data from one or more sensors of the sensor subsystem; process the sensor data to determine a relative position of two or more of a distal tip of a pipette tip affixed to a pipette releasably engaged with the pipette mount, an air-liquid interface of a fluid within a tube arranged in the tube mount, and a biological mass within the tube; and translate the plunger action arm and the pipette mount based on an evaluation of the processed sensor data and at least one respective threshold criterion, wherein translation of the plunger action arm depresses or releases a plunger of a pipette, and wherein translation of the pipette mount moves the pipette mount toward or away from the tube mount.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ15. The system of claim 14, wherein, when the evaluation indicates the processed sensor data satisfy the at least one respective threshold criterion, the processing circuitry is configured to translate the plunger action arm and the pipette mount by actuating the first actuator to move the pipette mount toward the tube holder, and actuating the second actuator to move the plunger action arm away from the tube holder.

16. The system of claim 14, wherein the at least one respective threshold criterion includes one or more of a desired relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid, a desired relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube, and a desired relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube.

17. The system of claim 16, wherein the desired relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid is about - 1 mm to about - 20 mm.

18. The system of claim 16, wherein the desired relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube is about + 1 mm to about + 20 mm.

19. The system of claim 16, wherein the desired relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube is about + 0.5 mm to about + 5 mm.

20. The system of claim 14, wherein, when the evaluation indicates the processed sensor data does not satisfy the at least one respective threshold criterion, the processing circuitry is configured to translate the plunger action arm and the pipette mount by actuating the first actuator to move the pipette mount away from the tube holder, and ceasing actuation of the second actuator.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ21. The system of claim 14, wherein, when the evaluation indicates the processed sensor data satisfy the at least one respective threshold criterion, the processing circuitry is configured to translate the plunger action arm and the pipette mount at respective translation rates.

22. The system of claim 14, wherein the processed sensor data includes at least one of a relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid, a relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube, and a relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube.

23. The system of claim 14, wherein, when the received sensor data comprises image data, the processing circuitry is configured to process the sensor data by image processing to determine the relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid, the relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube, and the relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube.

24. The system of claim 14, wherein, when the received sensor data comprises image data, the processing circuitry is configured to process the sensor data by image processing to determine an absolute position of the distal tip of the pipette tip, the air-liquid interface of the fluid, and an uppermost end of the biological mass within the tube.

25. The system of claim 24, wherein the processing circuitry is configured to determine, based on the absolute position of the distal tip of the pipette tip, the air-liquid interface of the fluid, and the uppermost end of the biological mass within the tube, the relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid, the relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube, and the relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ26. The system of claim 14, wherein the processing circuitry is further configured to process the sensor data by identifying an absolute position of one or more of the distal tip of the pipette tip affixed to the pipette releasably engaged with the pipette mount, the air-liquid interface of the fluid within the tube arranged in the tube mount, and an uppermost end of the biological mass within the tube.

27. The system of claim 14, wherein the tube mount is configured to receive a plurality of centrifuge tubes, and wherein the processing circuitry is further configured to process the sensor data by identifying an average absolute position of one or more of the distal tip of the pipette tip affixed to the pipette releasably engaged with the pipette mount, the air-liquid interface of the fluid within the tube arranged in the tube mount, and an uppermost end of the biological mass within the tube.

28. The system of claim 1, wherein the tube mount is configured to receive at least one tube comprising a biological mass.

29. The system of claim 28, wherein the biological mass comprises pathogens, food debris, cells, bacteria, protein, and viruses.

30. The system of claim 1, wherein a length of the frame defines an axis of travel of the pipette mount and the plunger action arm.

31. The system of claim 1, wherein the first actuator and the second actuator of the actuator subsystem are each selected from the group consisting of: a stepper motor; a brushed direct current (DC) motor, a brushed DC motor, an alternating current motor, a stepper motor, a servo motor, a universal motor, a linear motor, a hydraulic motor, and a pneumatic motor.

32. The system of claim 1, wherein the frame comprises a rail.

33. The system of claim 32, wherein the actuator subsystem is coupled to the rail.

34. The system of claim 1, wherein the frame is coupled to a base.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ35. The system of claim 34, wherein the base is a housing that comprises the sensor subsystem and the actuator subsystem.

36. The system of claim 35, wherein the base comprises a control panel to control operation of the system.

37. The system of claim 36, wherein the control panel comprises one or more user interfaces.

38. The system of claim 37, wherein the one or more user interfaces comprise one or more of a button(s), a dial(s), a touch screen(s), a switch(es), a slider(s), a trackpad(s), and a wheel(s).

39. The system of claim 34, wherein the base comprises a power source selected from at least one of a battery, electrical cord, and solar power.

40. The system of claim 34, wherein the tube mount is couplable to the base via one or more of a press-fit, a snap-fit, a magnet, a fastener, a screw, a rotational coupling, an adhesive, and welding.

41. The system of claim 32, wherein the tube mount is couplable to the rail of the frame via one or more of a press-fit, a snap-fit, a magnet, a fastener, a rotational coupling, an adhesive, and welding.

42. The system of claim 1, wherein the tube mount further comprises a lever to cap and uncap at least one tube within the tube mount.

43. The system of claim 4, wherein the tube holder is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber.

44. The system of claim 1, wherein the frame is made of a material comprising one or more of a metal, polymer, ceramic, and composite.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ45. The system of claim 4, wherein the first actuator and the second actuator comprise a linear actuator, a rotary actuator, a hydraulic actuator, an electronic actuator, and a thermal actuator.

46. The system of claim 1, wherein the processing subsystem comprises a processing circuitry configured to: receive data from a user interface of the system; and translate the plunger action arm and the pipette mount based on the received data.

47. The system of claim 46, wherein the user interface of the system comprises at least one of a button(s), a dial(s), a touch screen(s), a switch(es), a slider(s), a trackpad(s), and a wheel(s).

48. The system of claim 46, wherein the received data indicates at least one of a size of a tube within the tube rack, a volume of supernatant within the tube, a desired volume of the supernatant in the tube after extraction, and a size of a biological mass within the tube.

49. The system of claim 48, wherein the size of the tube within the tube rack is a 1.5 mL tube.

50. The system of claim 46, wherein the received data indicates a viscosity of a supernatant within a tube within the tube rack.

51. The system of claim 14, wherein the received sensor data comprises image data, and wherein the processing circuitry is configured to process the image data to by image processing.

52. The system of claim 51, wherein the image processing generates a binary image of the tube arranged in the tube mount.

53. The system of claim 51, wherein the image processing comprises linear filtering, segmentation, edge detection, image compression, contrast enhancement, feature extraction, Gaussian image processing, Hidden Markov models, object detection and recognition, pattern recognition, and neural networks.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ54. The system of claim 51, wherein the processing circuity obtains, via the image processing, a signal of a meniscus of the fluid within the tube as the air-liquid interface.

55. A tube rack, comprising: a planar material having a plurality of apertures therethrough, the plurality of apertures being sized to receive a tube; and at least one alignment feature disposed on the planar material proximal each of the plurality of apertures to orient the tube received therein.

56. A system comprising tube rack of claim 55, comprising a tube holder configured to receive the tube rack.

57. The system of claim 56, further comprising a tube mount configured to receive the tube holder, the tube mount being mountable to the frame.

58. The tube rack of claim 55, wherein the plurality of apertures is designed to accept a plurality of tubes.

59. The system of claim 57, wherein the tube mount comprises a lever to uncap or cap the plurality of tubes.

60. The tube rack of claim 58, wherein the tube rack can be adjusted to fit tubes of different sized.

61. The tube rack of claim 55, wherein the tube rack has grasping features.

62. The tube rack of claim 55, wherein the at least one alignment feature comprises locating pins, bushings, dowels, centerlines, reference marks, fixtures, linear guides, rails, magnetic clamps, magnetic bases, and alignment algorithms.

63. The tube rack of claim 55, wherein the tube rack is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ64. A method for detecting pathogens in a food sample, comprising: obtaining a food sample suspected of comprising at least one pathogen; processing the food sample to generate a liquid food sample solution; isolating a biological mass from a filtrate of the liquid food sample solution; and detecting a presence of the at least one pathogen within the biological mass via a biological assay.

65. The method of claim 64, wherein processing comprises adding a liquid solution.

66. Th method of claim 65, wherein processing comprises mixing, cutting, stomaching, emulsifying, blending, grinding, and mincing.

67. The method of claim 64, wherein isolating is performed using the system of claim 1.

68. The method of claim 64, wherein the at least one pathogen comprises bacteria, viruses, parasites, fungi, and protozoa.

69. The method of claim 64, wherein the at least one pathogen comprises Salmonella, Escherichia coli, Listeria monocytogenes, Campylobacter, Clostridium perfringens, Vibrio, Staphylococcus aureus, Norovirus, Hepatitis A virus, Giardia, Cryptosporidium, Toxoplasma gondii, and Trichinella.

70. The method of claim 64, wherein biological assay comprises at least one of a culturebased technique, immunoassay, PCR, biomarker, biosensor, and DNA microarray.

71. The method of claim 64, wherein the biological assay comprises PCR.

72. The method of claim 64, wherein the food sample is incubated before processing.

73. The method of claim 64, wherein isolating the biological mass comprises: retrieving a filtrate from the liquid food sample solution; centrifuging the filtrate; recovering a supernatant from the centrifuged filtrate; and resuspending the biological mass within a medium.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ74. A system for automated pipetting, comprising: a frame, comprising: a tube mount; a plunger action arm; a pipette mount; and an actuator subsystem comprising a first actuator and second actuator, the first actuator configured to control translation of the tube mount, and the second actuator configured to control translation of the plunger action arm; a sensor subsystem; and a processing subsystem.

75. The system of claim 74, wherein the pipette mount comprises a magnetic surface for magnetically engaging a pipette.

76. The system of claim 75, wherein the pipette is a single-channel pipette or a multichannel pipette.

77. The system of claim 74, wherein the tube mount is configured to receive a tube holder comprising at least one centrifuge tube therein.

78. The system of claim 77, wherein the at least one centrifuge tube is fitted within a tube rack configured to be received by the tube holder.

79. The system of claim 78, wherein the tube rack comprises one or more apertures configured to receive the at least one centrifuge tube.

80. The system of claim 79, wherein the tube rack further comprises at least one alignment feature proximal to a respective aperture of the one or more apertures to orient the at least one centrifuge tube within the tube rack.

81. The system of claim 80, wherein the at least one alignment feature comprises one or more of locating pins, bushings, dowels, centerlines, reference marks, fixtures, linear guides, rails, magnetic clamps, magnetic bases, and alignment algorithms.ATTORNEY DOCKET NO. : PTRK-009 / 00WO82. The system of claim 74, wherein the actuator subsystem further comprises a third actuator configured to control translation of the pipette mount.

83. The system of claim 74, wherein the frame further comprises one or more buttons actuatable to control operation of the system.

84. The system of claim 83, wherein the one or more buttons includes at least one button associated with a predetermined size of a respective centrifuge tube and / or a predetermined volume of supernatant remaining in the respective centrifuge tube after extraction.

85. The system of claim 74, wherein the sensor subsystem comprises one or more visible light sensors.

86. The system of claim 74, wherein the sensor subsystem comprises one or more of a visible light sensor, ultrasound sensor, image sensor, infrared sensor, temperature sensor, proximity sensor, pressure sensor, touch sensor, color sensor, flow sensor, level sensor, digital sensor, analog sensor, and a force sensor.

87. The system of claim 74, wherein the processing subsystem comprises a processing circuitry configured to: receive sensor data from one or more sensors of the sensor subsystem; process the sensor data to determine a relative position of two or more of a distal tip of a pipette tip affixed to a pipette releasably engaged with the pipette mount, an air-liquid interface of a fluid within a tube arranged in the tube mount, and a biological mass within the tube; and translate the plunger action arm and the tube mount based on an evaluation of the processed sensor data and at least one respective threshold criterion, wherein translation of the plunger action arm depresses or releases a plunger of a pipette, and wherein translation of the tube mount moves the tube mount toward or away from the pipette mount.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ88. The system of claim 87, wherein, when the evaluation indicates the processed sensor data satisfy the at least one respective threshold criterion, the processing circuitry is configured to translate the plunger action arm and the tube mount by actuating the first actuator to move the tube mount toward the pipette mount, and actuating the second actuator to move the plunger action arm away from the tube mount.

89. The system of claim 87, wherein the at least one respective threshold criterion includes one or more of a desired relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid, a desired relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube, and a desired relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube.

90. The system of claim 89, wherein the desired relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid is about - 1 mm to about - 20 mm.

91. The system of claim 89, wherein the desired relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube is about + 1 mm to about + 20 mm.

92. The system of claim 89, wherein the desired relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube is about + 0.5 mm to about + 5 mm.

93. The system of claim 87, wherein, when the evaluation indicates the processed sensor data does not satisfy the at least one respective threshold criterion, the processing circuitry is configured to translate the plunger action arm and the tube mount by actuating the first actuator to move the tube mount away from the pipette mount, and ceasing actuation of the second actuator.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ94. The system of claim 87, wherein, when the evaluation indicates the processed sensor data satisfy the at least one respective threshold criterion, the processing circuitry is configured to translate the plunger action arm and the tube mount at respective translation rates.

95. The system of claim 87, wherein the processed sensor data includes at least one of a relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid, a relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube, and a relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube.

96. The system of claim 87, wherein, when the received sensor data comprises image data, the processing circuitry is configured to process the sensor data by image processing to determine the relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid, the relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube, and the relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube.

97. The system of claim 87, wherein, when the received sensor data comprises image data, the processing circuitry is configured to process the sensor data by image processing to determine an absolute position of the distal tip of the pipette tip, the air-liquid interface of the fluid, and an uppermost end of the biological mass within the tube.

98. The system of claim 97, wherein the processing circuitry is configured to determine, based on the absolute position of the distal tip of the pipette tip, the air-liquid interface of the fluid, and the uppermost end of the biological mass within the tube, the relative position of the distal tip of the pipette tip and the air-liquid interface of the fluid, the relative position of the distal tip of the pipette tip and an uppermost end of the biological mass within the tube, and the relative position of the air-liquid interface of the fluid and the uppermost end of the biological mass within the tube.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ99. The system of claim 87, wherein the processing circuitry is further configured to process the sensor data by identifying an absolute position of one or more of the distal tip of the pipette tip affixed to the pipette releasably engaged with the pipette mount, the air-liquid interface of the fluid within the tube arranged in the tube mount, and an uppermost end of the biological mass within the tube.

100. The system of claim 87, wherein the tube mount is configured to receive a plurality of centrifuge tubes, and wherein the processing circuitry is further configured to process the sensor data by identifying an average absolute position of one or more of the distal tip of the pipette tip affixed to the pipette releasably engaged with the pipette mount, the air-liquid interface of the fluid within the tube arranged in the tube mount, and an uppermost end of the biological mass within the tube.

101. The system of claim 74, wherein the tube mount is configured to receive at least one tube comprising a biological mass.

102. The system of claim 101, wherein the biological mass comprises pathogens, food debris, cells, bacteria, protein, and viruses.

103. The system of claim 74, wherein a length of the frame defines an axis of travel of the pipette mount and the plunger action arm.

104. The system of claim 74, wherein the first actuator and the second actuator of the actuator subsystem are each selected from the group consisting of: a stepper motor; a brushed direct current (DC) motor, a brushed DC motor, an alternating current motor, a stepper motor, a servo motor, a universal motor, a linear motor, a hydraulic motor, and a pneumatic motor.

105. The system of claim 74, wherein the frame comprises a rail.

106. The system of claim 105, wherein the actuator subsystem is coupled to the rail.

107. The system of claim 74, wherein the frame is coupled to a base.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ108. The system of claim 107, wherein the base is a housing that comprises the sensor subsystem and the actuator subsystem.

109. The system of claim 108, wherein the base comprises a control panel to control operation of the system.

110. The system of claim 109, wherein the control panel comprises one or more user interfaces.

111. The system of claim 110, wherein the one or more user interfaces comprise one or more of a button(s), a dial(s), a touch screen(s), a switch(es), a slider(s), a trackpad(s), and a wheel(s).

112. The system of claim 107, wherein the base comprises a power source selected from at least one of a battery, electrical cord, and solar power.

113. The system of claim 107, wherein the tube mount is couplable to the base via one or more of a press-fit, a snap-fit, a magnet, a fastener, a screw, a rotational coupling, an adhesive, and welding.

114. The system of claim 105, wherein the tube mount is couplable to the rail of the frame via one or more of a press-fit, a snap-fit, a magnet, a fastener, a rotational coupling, an adhesive, and welding.

115. The system of claim 74, wherein the tube mount further comprises a lever to cap and uncap at least one tube within the tube mount.

116. The system of claim 77, wherein the tube holder is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber.

117. The system of claim 74, wherein the frame is made of a material comprising one or more of a metal, polymer, ceramic, and composite.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ118. The system of claim 74, wherein the first actuator and the second actuator comprise a linear actuator, a rotary actuator, a hydraulic actuator, an electronic actuator, and a thermal actuator.

119. The system of claim 74, wherein the processing subsystem comprises a processing circuitry configured to: receive data from a user interface of the system; and translate the plunger action arm and the pipette mount based on the received data.

120. The system of claim 119, wherein the user interface of the system comprises at least one of a button(s), a dial(s), a touch screen(s), a switch(es), a slider(s), a trackpad(s), and a wheel(s).

121. The system of claim 119, wherein the received data indicates a size of a tube within the tube rack, a volume of supernatant within the tube, a desired volume of the supernatant in the tube after extraction, and a size of a biological mass within the tube.

122. The system of claim 121, wherein the size of the tube within the tube rack is a 1.5 mL tube.

123. The system of claim 119, wherein the received data indicates a viscosity of a supernatant within a tube within the tube rack.

124. The system of claim 87, wherein the received sensor data comprises image data, and wherein the processing circuitry is configured to process the image data to by image processing.

125. The system of claim 124, wherein the image processing generates a binary image of the tube arranged in the tube mount.

126. The system of claim 124, wherein the image processing comprises linear filtering, segmentation, edge detection, image compression, contrast enhancement, feature extraction, Gaussian image processing, Hidden Markov models, object detection and recognition, pattern recognition, and neural networks.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ127. The system of claim 124, wherein the processing circuity obtains, via the image processing, a signal of a meniscus of the fluid within the tube as the air-liquid interface.

128. A tube rack, comprising: a plurality of ring-like structures having apertures therethrough, the apertures being sized to receive a tube, the plurality of ring-like structures being connected sequentially by a respective flexible connector; and at least one alignment feature disposed proximal each respective aperture to orient the tube received therein.

129. The tube rack of claim 128, wherein the plurality of apertures is designed to accept a plurality of tubes.

130. The tube rack of claim 128, wherein the tube rack comprises at least one grasping feature.

131. The tube rack of claim 130, wherein the at least one grasping feature comprises a tab proximal a first one of the plurality of ring-like structures.

132. The tube rack of claim 131, wherein the tab comprises indicia to indicate an orientation of the tube rack.

133. The tube rack of claim 128, wherein the at least one alignment feature comprises locating pins, bushings, dowels, centerlines, reference marks, fixtures, linear guides, rails, magnetic clamps, magnetic bases, and alignment algorithms.

134. The tube rack of claim 128, wherein the tube rack is made of a material comprising one or more of a metal, alloy, polymer, ceramic, composite, glass, silicon, and rubber.

135. The tube rack of claim 128, wherein each respective flexible connector permits the plurality of ring-like structures to flex in at least one axis.

136. The tube rack of claim 135, wherein the at least one axis is at least two axes.ATTORNEY DOCKET NO. : PTRK-009 / 00WQ137. The tube rack of claim 128, wherein the plurality of ring-like structures comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, or at least twelve ring-like structures.

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