JP2007523284A - Material transfer system, computer program product and method - Google Patents

Abstract

The present invention provides a material transfer system configured to transfer a substantially uniform amount of material to and / or from the material site and to minimize periodic fluctuations in the amount of material transferred. Related computer program products and methods are also provided.

Description

Copyright notice 37C. F. R. In accordance with § 1.71 (e), Applicant notes that some of this disclosure contains material that is subject to copyright protection. The copyright owner has no objection to anyone who reproduces a patent document or patent disclosure found in the Patent and Trademark Office patent file or record, but otherwise owns all copyright rights. Hold.

CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of US Provisional Application No. 60 / 527,125 (filing date: December 4, 2003), the entire disclosure of which is incorporated for all purposes.

FIELD OF THE INVENTION Generally, the present invention provides a material transfer system and associated method for accurately transferring a selected amount of material to and / or from a material site.

Background of the Invention Rotary peristaltic pumps are used to transport materials in a wide range of applications, including the manufacture of pharmaceuticals, chemicals, foods, and beverages. In a typical rotary peristaltic pump system, a series of circular conduits contact one or more material conduits (eg, flexible tubes or hoses) such that the conduits are compressed against a compression surface such as a curved wall. Rotate the roller or shoe. This creates a moving region of compression along the length of the conduit, pulling material from the moving region upstream of the conduit, pushing material from the moving region downstream of the conduit, and transferring material through the conduit. One advantage of peristaltic pumps is that material can be transferred through a conduit without contact between the internal components of the pump and the material being transferred. For example, this reduces the risk of contamination of the transfer material.

In general, periodic variations in the amount of material transferred by the rotary peristaltic pump are observed, which can lead to inaccurate material transfer, especially when trying to transfer a plurality of uniform amounts. In particular, the amount of material transferred during an angular displacement and displacement cycle, typically when the lead roller (ie, the roller most in contact with the material conduit in a particular displacement cycle) applies a constant pressure to the material conduit. There is a substantially proportional relationship between. However, this relationship tends to be non-proportional when the lead roller experiences an opening event in which the pressure applied to the material conduit by the lead roller is reduced to zero. This can result in repetitive abnormal or periodic variations in the function relating the amount of material movement and the angular displacement of the pump, which can lead to inaccurate material distribution if this is not taken into account.
US patent application Ser. No. 10 / 350,905 US Pat. No. 6,393,338

  It is therefore clearly desirable to have a system that takes into account periodic variations in the amount of material transferred by a rotary peristaltic pump. These and various other features of the present invention will become apparent after reviewing the entire disclosure below.

SUMMARY OF THE INVENTION In general, the present invention relates to a material transfer system and method for reliably transferring a selected amount of material using a peristaltic pump, including microliter volumes of fluid material. The approach to reproducibly transfer the desired amount of material described here can easily take into account the periodic variations generally observed in the amount of material transferred by the peristaltic pump, and generally many existing Less complex to implement than transfer technology. For example, according to certain aspects, the system of the present invention is configured to perform substantially the same roller opening event for each transfer of material to minimize roller opening, which is a source of variation in transfer. . In certain aspects, the systems and methods of the present invention further provide synchronized and accurate transfer for multiple quantities of material to achieve a high level of throughput. Aspects of the present invention also minimize material carry-over between material sites (eg, between wells located in a multi-well container), for example, cross-contamination of those sites and transfer of inaccurate amounts of material. Also included is a method for reducing the risk. The present invention also provides related computer program products that can be used to implement the methods and systems described herein.

  In one aspect, the present invention provides a material transfer system. The system includes at least one peristaltic pump having a rotatable roller support that supports at least two rollers (eg, a fixed roller, a rotatable roller, or a combination thereof) and a roller support operably connected to the peristaltic pump. And at least one motor for rotation. The system also includes at least one controller operably connected to the motor. When one or more material conduits are operably connected to the peristaltic pump and the peristaltic pump transfers material through the material conduit, an amount of material corresponding to the incremental rotation is transferred to at least one material site (eg, material container, substrate surface). The controller supports at least one roller increment by at least one rotation increment substantially corresponding to an integer multiple of the angular distance between adjacent rollers supported by the roller support. Configured to rotate. In general, the same rotation increment transfers a substantially uniform amount of material to or from the material site. Furthermore, generally the rotation increment is not compensated for the flow rate characteristics of the system. In certain aspects, the system further comprises at least one material conduit operably connected to the peristaltic pump. Typically, the controller is configured to perform substantially the same roller opening from the material conduit for each material transfer to minimize periodic fluctuations in the material transfer. Optionally, the system also comprises at least one detector operably connected to the controller. The detector is configured to detect a detectable signal generated at one or more material sites.

  In certain aspects, the system further comprises at least one positioning component operably connected to the controller. The positioning component has a structure for movably positioning at least one material conduit and / or one or more material sites relative to each other. In general, the positioning component comprises at least one object holder structured to support the material site. In certain aspects, the system further comprises a material conduit operably connected to the positioning component and the peristaltic pump. Optionally, the system further comprises at least one cleaning component operably connected to the controller. The cleaning component has a structure for cleaning the material conduit when the material conduit is operably connected to at least the positioning component and the positioning component moves the material conduit to at least the vicinity of the cleaning component. In certain aspects, the system also includes at least one attachment component that attaches at least the peristaltic pump, the motor, and the positioning component to each other.

  In another aspect, the present invention provides a material transfer system comprising at least one material conduit and at least one peristaltic pump operably connected to the material conduit. The peristaltic pump includes a rotatable roller support that supports at least two rollers. Material transfer systems are typically automated. The system also includes at least one feedback component operably connected to the peristaltic pump. The feedback component comprises at least one motor that rotates the roller support. The system also includes at least one controller operably connected to the feedback component. The controller is configured to control the angular distance between adjacent rollers supported by the roller support such that the amount of material transferred through the material conduit to or from at least one material site corresponds to the rotation increment. The roller support is configured to rotate at least one rotation increment substantially corresponding to an integer multiple. In general, this rotation increment corresponds to a material volume of at least 0.1 μl. In addition, generally the same rotation increment transfers a substantially uniform material volume to or from the material site. In general, the rotation increment is not compensated for the flow rate characteristics of the system. In certain aspects, the material transfer system further comprises at least one detector operably connected to the controller. The detector is configured to detect a detectable signal generated at one or more material sites.

  The peristaltic pump provided in the material transfer system of the present invention includes various embodiments. For example, in certain embodiments, the peristaltic pump comprises a multi-channel peristaltic pump. Typically, peristaltic pumps are configured to reversibly transfer an amount of material to or from the material site. Also, peristaltic pumps typically generate a material flow rate sufficient to dispense material from the end in a non-contact manner, at least near the end of the material conduit. Further, the roller support typically supports 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30 or more rollers, for example. Generally, the moment of inertia of the roller support is minimized to prevent a certain amount of material from sticking to the exterior of the material conduit when the peristaltic pump transports the material through the material conduit. Furthermore, in general, the angular distance between adjacent roller pairs supported by a roller support is substantially equal to each other. For example, adjacent rollers that are generally supported by a roller support are positioned at most 180 ° apart from each other. In some embodiments, the roller support is interchangeable with at least one other roller support. In embodiments where the roller is rotatable, the peristaltic pump optionally includes a gear mechanism that rotates the rotatable roller, for example, to minimize wear of the material conduit when the motor rotates the roller support.

  In certain aspects, the feedback component comprises at least one drive mechanism operably connected to the motor. Typically, the drive mechanism comprises at least one control component that provides position feedback control of the motor. In general, the motor comprises at least one position encoder and at least one gear reduction component. For example, the motor typically consists of a servo motor or a stepping motor. In certain aspects, the feedback component further comprises one or more weigh scales operably connected to the controller. The weigh scale detects the weight of material placed at one or more material sites.

  Generally, the controller is configured to provide substantially the same roller opening from the material conduit for each material transfer to minimize periodic fluctuations in the material transfer. In embodiments where the roller is rotatable, optionally the controller is further configured to rotate at least one of the rollers supported by the roller support. In these embodiments, the roller typically rotates in a direction opposite to the direction of rotation of the roller support to minimize material conduit wear. For example, the roller and roller support typically rotate at substantially equal absolute speeds. In certain aspects, the controller applies at least one negative pressure pulse at least at the end of the material conduit after rotating the roller support by rotational increments to prevent a certain amount of material from adhering to the exterior of the material conduit. Add to the neighborhood. In general, the moment of inertia of the roller support is further minimized to prevent a certain amount of material from sticking to the exterior of the material conduit.

The material conduits provided by the system of the present invention also include various embodiments. In some embodiments, for example, the cavity disposed through the material conduit has a cross-sectional dimension of 1 mm to 10 ⁵ μm. Typically, the material transfer system comprises a plurality of material conduits, the ends of at least two of the material conduits being simultaneously spaced in different wells disposed in at least one multi-well container at a constant distance from each other. Communicate. In some embodiments, two or more of the plurality of material conduits included in the material transfer system communicate with different material sources.

  In certain embodiments, at least one end of the material conduit includes at least one tip. In these embodiments, optionally the tip is integrated with the end. In certain aspects, the cavity disposed through the chip has at least two different cross-sectional dimensions. Typically, at least a portion of the tip is tapered. In some embodiments, at least a portion near the end of the material conduit is substantially straight. The length of the substantially straight portion of the material conduit is 60 mm or more. In some embodiments, the end of the material conduit and the tip are connected by an insert, for example, such that the material conduit and the tip are in communication with each other. In some of these embodiments, the insert portion is inserted into the end and tip portion, while in other embodiments, the end and tip portion is inserted into the insert portion. Generally, the insert is made of a material that is at least less flexible than the material conduit.

  In certain aspects, the material transfer system further comprises at least one positioning component operably connected to the controller. In general, the positioning component has a structure in which material conduits and / or material sites are movably arranged relative to one another. For example, optionally the positioning component comprises at least one object holder structured to support the material site. Also, the controller typically rotates the roller support simultaneously with the material conduit and / or the material conduit and / or the material site in synchronism with the relative movement of the material conduit and / or material site. And / or configured to displace the material sites from one another.

  In one aspect, the positioning component comprises at least one X / Y axis linear motion table operably connected to at least one position feedback control drive, the position feedback control drive along the X and Y axes. Controls the motion of the X / Y axis linear motion table. Typically, the positioning component comprises at least one object holder operably connected to an X / Y axis linear motion table, the object holder having a structure that supports the material site. In certain aspects, the positioning component comprises at least one Z-axis linear motion component having at least one material conduit support head that supports at least a portion of the material conduit and along the Z-axis. Moving. Generally, the Z-axis linear motion component comprises at least one solenoid. Typically, the positioning component is configured to move the material conduit support head at a rate sufficient to eliminate adherent material adhering to the exterior of the material conduit.

  In certain aspects, the material transfer system further comprises at least one cleaning component operably connected to the controller, wherein the cleaning component moves the material conduit when the positioning component moves the material conduit at least in the vicinity of the cleaning component. It has a structure for cleaning. In some of these aspects, for example, the cleaning component comprises a vacuum chamber having at least one opening, and the positioning component moves the material conduit into or near the opening, thereby applying an applied vacuum. Removes the adherent material from the outer surface of the material conduit. Typically, the outer cross-sectional dimension of the material conduit is smaller than the cross-sectional dimension of the opening.

  In certain aspects, the material transfer system further comprises at least one attachment component that attaches at least the peristaltic pump, the feedback component, and the positioning component to each other. Typically, the mounting component is substantially rigid.

  In another aspect, the present invention provides (i) a rotation increment substantially corresponding to an integer multiple of the angular distance between adjacent rollers supported by the roller support of a peristaltic pump; (ii) a cross-sectional dimension of the material conduit; For receiving one or more input parameters selected from the group consisting of :) the amount of material transferred to or from the material site; and (iv) the angular distance between adjacent rollers supported by the roller support of the peristaltic pump. A computer program product comprising a computer readable medium having one or more logical instructions is provided. The computer program product also has an amount of material corresponding to the incremental rotation at least one material site or when one or more material conduits are operably connected to the peristaltic pump and the peristaltic pump transfers material through the material conduit. One or more rotating the peristaltic pump roller support by rotational increments substantially corresponding to an integral multiple of the angular distance between adjacent rollers supported by the peristaltic pump roller support for transfer from at least one material site Contains logic instructions. In a particular aspect, the computer program product further includes at least one logical instruction that moves the X / Y axis linear motion table and the Z axis motion component in synchronization with the rotation of the roller support.

  In another aspect, the invention relates to a method for transferring material. The method includes providing a material transfer system comprising at least one controller operably connected to at least one motor operably connected to at least one peristaltic pump. The peristaltic pump includes a rotatable roller support that supports at least two rollers and is operably connected to at least one material conduit. Typically the system is automated. The method also includes transferring material (cell suspension, reagent, buffer, solid support suspension, etc.) through the material conduit, wherein the controller is to at least one material site or to at least one material site. The roller support is rotated by at least one rotation increment that substantially corresponds to an integer multiple of the angular distance between adjacent rollers supported by the roller support such that the amount of material transferred from the roller support corresponds to the rotation increment. Typically, the controller rotates the roller support so that shear effects on the transfer material (eg, cells) in the material are minimized. Typically, the material is transferred to the material site without the material conduit contacting the material site. Generally, a certain amount of material contains at least 0.1 μl of material. In certain aspects, the system further comprises at least one feedback component operably connected to the motor, the feedback component providing position feedback control for the peristaltic pump. In general, the controller provides substantially the same roller opening from the material conduit for each material transfer to minimize periodic fluctuations in the material transfer. In general, the rotation increment is not compensated for the flow rate characteristics of the system. Typically, the same rotation increment transfers a substantially uniform amount of material to or from the material site. In a particular aspect, the method applies at least one negative pressure pulse by the controller after rotating the roller support by rotational increments to prevent a certain amount of material from adhering to the exterior of the material conduit. And adding in the vicinity of the ends of the.

  In certain aspects, the system further comprises at least one positioning component operably connected to the controller, the positioning component having a structure that movably positions the material conduits and / or material sites relative to one another. Typically, the material conduit is moved at a rate sufficient to remove any adherent material deposited outside the positioning component material conduit. Typically, the method includes moving the material conduit at a rate sufficient to remove any adherent material attached to the exterior of the material conduit. In some aspects, the positioning component can cause the material conduit to contact the at least one other object to remove the adherent material from the exterior of the material conduit, if any. Move. For example, optionally the other object comprises a portion of a well of a multi-well container.

  In certain aspects, the material site includes at least one multi-well container, the method transfers at least a first amount of material to at least a first well of the multi-well container, and the material conduit is at least a second of the multi-well container. Moving material conduits and / or material sites relative to each other, for example by a positioning component, and transferring at least a second amount of material to a second well of a multi-well container. . Typically, the moving step and the at least one transfer step are performed substantially simultaneously with each other. Typically, the step of moving includes placing a portion of the material conduit above or in the second well.

  In certain aspects, the system includes a plurality of material conduits operably connected to the peristaltic pump, and the method includes transferring a plurality of amounts of material to or from the material sites through the material conduit. In these embodiments, generally two or more of the material conduits are in substantial communication with different material sources. Typically, multiple amounts of material are transferred substantially simultaneously. In some embodiments, the material site comprises at least one multiwell container, and the ends of at least two of the material conduits are spaced by a distance corresponding to the distance between at least two wells disposed in the multiwell container. I can make it. In these aspects, the method generally includes simultaneously transferring material to or from the two wells through the two material conduits. In general, a material site comprises at least one material container and / or at least one substrate surface. Typically, the material container consists of a multi-well material container having, for example, 6, 12, 24, 48, 96, 192, 384, 768, 1536 wells or more. Optionally, the substrate surface includes a membrane surface.

  In another aspect, the present invention provides a method for transferring material to a material site. The method includes providing a material transfer system comprising at least one material conduit and at least one pump operatively connected to the material conduit and transferring material through the material conduit. The material transfer system also includes at least one positioning component that is operably connected to the material conduit to move the material conduit. The material transfer system also includes at least one controller operably connected to the pump and the positioning component. The controller moves material through the material conduit by a pump and moves the material conduit by a positioning component. The method also includes transporting the material (eg, fluid material) through the material conduit such that an amount of material adheres to the distal portion of the material conduit to form a predetermined amount of adherent material. The method also includes accelerating at least the distal portion of the material conduit by the positioning component toward the material site such that a predetermined amount of adherent material is transferred from the distal portion of the material conduit to the material site, and the positioning component. Decelerating the distal portion of the material conduit. In general, a material site includes at least one well of a multi-well container. Typically, the deceleration step includes removing a predetermined amount of adherent material from the end portion of the material conduit. Typically, a predetermined amount of adherent material is transferred to the material site without contacting the end portion of the material conduit and the material site. In certain embodiments, the material comprises a cell suspension and the method minimizes shear effects on the transferred cells.

Detailed description Definitions Before describing the present invention in detail, it is to be understood that the present invention is not limited to a particular system or method and may, of course, vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. Moreover, unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In describing the present invention, the following terms and grammatical variations are used in accordance with the definitions below.

  The term “material” refers to a substance in essentially any physical state. For example, the material can take the form of a gas, liquid, semi-fluid, paste, powder, and combinations thereof. Further, for example, in certain embodiments of the invention, the material comprises cells and / or reagent suspensions.

  The term “angular distance” or “angular displacement” refers to the angle at which the rotating body rotates. For example, in one aspect of the invention, the rotatable roller support of the peristaltic pump rotates by rotational increments that substantially correspond to an integer multiple of the angular distance between adjacent rollers supported by the roller support.

  The term “moment of inertia” refers to a measure of the body's resistance to angular acceleration about a given axis, which is the sum of the product of each mass element in the body and the square of its distance from that axis. be equivalent to.

  The expression “reversibly transported” means, for example, that a material or part of it can be moved from the material site after distribution, for example, at a material site, or distributed from one material site to another material site, etc. This refers to the process of transporting various materials. For example, in certain embodiments, fluid material is aspirated from a material site (eg, a multi-well plate or other source of fluid material) and other sites (eg, wells of a multi-well plate, substrate surface, fluid material waste container, etc.) Distributed to. Typically, reversible material transfer is accomplished by rotating the peristaltic pump roller support in a direction opposite to the direction of rotation of the roller support to transfer material to a particular material site.

  The expression “non-contact material distribution” refers to a material distribution process in which the material conduit of the material transfer system does not contact the material site or the material located at the material site when the material is distributed from the material conduit.

  The term “feedback component” refers to a component of the system that provides information about one or more other components of the system. For example, in certain embodiments, the material transfer system of the present invention includes a feedback component with a motor that rotates the roller support of the peristaltic pump. In these aspects, the feedback component is typically a controller operatively connected to the feedback component, typically information regarding the position of the roller support, for example, so that the roller support can be rotated by rotation increments selected by the controller. To provide. In some aspects, the feedback component provides information such as the weight of material present at a particular material site. For further details regarding these types of feedback components optionally adapted for use in the material transfer system of the present invention, see, eg, US Patent Application No. 10 / 350,905, “FLUID HANDRING METHODS AND SYSTEMS” by Micklash II et al. (Filed Jan. 24, 2003), incorporated herein by reference.

  The term “rotational increment” refers to the angular displacement of the roller support. For example, typically, the controller of the system of the present invention is an integer number of angular distances between adjacent rollers supported by a roller support, such that, for example, substantially the same roller opening occurs for each transfer of material. The roller support is configured to rotate by rotational increments substantially corresponding to the double. For example, in certain aspects, the user directly selects the rotation increment that the roller support rotates, while in another aspect, the system controller may select an appropriate rotation increment based on, for example, the input amount of material that the user wants to transfer. Composed.

  The expression “roller opening” or “opening event” refers to the process by which the roller of the roller support leaves contact with the material conduit during operation of the peristaltic pump. Typically, an opening event corresponds to a change in pressure applied by a roller experiencing opening from approximately maximum to substantially zero.

  The expression "integer multiple of the angular distance between adjacent rollers" is the product of the angular distance between adjacent rollers supported by the roller support of the peristaltic pump and an integer (ie a natural number, one of these numbers negative or zero). Say about. Typically, the controller of the system described herein is configured to rotate the roller support by rotational increments substantially corresponding to an integer multiple of the angular distance between adjacent rollers supported by the roller support. For example, if the roller support includes three rollers positioned 120 ° apart from each other and the selected integer is +2, the rotation increment of the roller support will be 240 °, while selecting for the same roller support If the resulting integer is +4, the roller support rotation increment will be 480 °, and so on. In general, the positive and negative signs in front of the selected integer indicate the relative direction of rotation of the roller support, eg, forward or reverse.

  A material conduit “communicates” with a material site if the material can be moved to and / or from the material site under pressure applied by, for example, a peristaltic pump.

  The expression “periodic variation” refers to repetitive changes in the output or other characteristics of a given device or system. There are typically periodic variations in the amount of material transferred by the rotary peristaltic pump, for example when the roller is released from the material conduit during a displacement cycle. More specifically, if the lead roller (ie, the roller that contacts the material conduit most quickly in a particular displacement cycle) applies a constant pressure to the material conduit, the angular displacement during the displacement cycle and the transfer material There is a substantially proportional relationship with the quantity. However, this relationship tends to be non-proportional when the lead roller experiences an opening event in which the pressure applied to the material conduit by the lead roller decreases to zero. This results in repetitive anomalies or periodic variations in the function relating material discharge and angular displacement of the pump.

  The term “top” generally refers to the highest point, level, surface, or device or system or device or system component in the case of a designed or intended operational use, such as the transfer of material from a source to a destination. Say about the part. In contrast, the term “bottom” generally refers to the lowest point, level, surface or portion of a device or system or component of a device or system in the case of design or intended operational use.

II. Introduction The present invention will be described with respect to a few specific embodiments, but this description is illustrative of the invention and is not to be construed as limiting the invention. Those skilled in the art can make various modifications to the embodiments of the present invention described herein without departing from the true scope of the present invention as set forth in the claims. For example, although the emphasis here is on the transfer of relatively small quantities or volumes (eg, milliliters, microliters, etc.) of material for clarity of explanation, the systems and methods of the present invention are essentially optional. It can be seen that the amount of material can be adapted to accurately transfer. It should also be noted that for the sake of better understanding, certain identical components are designated by the same reference letters and / or numbers throughout the various figures.

  In general, the material transfer system and method of the present invention comprises a peristaltic pump that rotates with acceleration, speed, and deceleration adjusted precisely to achieve accurate angular displacement. In addition, the systems and methods described herein typically take into account periodic fluctuations caused, for example, by roller opening events so that accurate and reproducible material transfer is achieved using a rotary peristaltic pump. For example, in certain aspects, the material transfer system is configured to minimize roller opening as a source of variation in material transfer by causing substantially the same roller open event for each transfer of material.

  For example, in general, when the reed pump roller applies a constant pressure to the material conduit to initiate and terminate the displacement cycle, there is a substantial difference between the angular displacement of the pump roller support and the amount of material transferred (eg, volume). There is a proportional relationship. In addition, while the reed roller begins to release from the material conduit, for example, another roller begins to engage the conduit (e.g. tubing), typically at least some material in the conduit is sucked back. When filling the gap left by the lead roller leaving the contact with the conduit, there is a period in which the transfer begins to become at least partially negative as a function of angular displacement. This is further illustrated in FIGS. 1A and B, where a pump roller support 100 supporting four rollers 102 is shown schematically. In FIGS. 1A and B, Ω and Ω ′ are the same size. As shown, the roller 102 presses the conduit 104 against the compression surface 106 to transfer material through the conduit 104. Arrow 108 indicates the direction of rotation of the roller support 100 and arrow 110 indicates the direction of material transfer through the conduit 104. FIG. 1B shows the change in the state of the conduit 104 after the pump has rotated the roller support 100 by the displacement Ω illustrated in FIG. 1A. As the progression from FIG. 1A to FIG. 1B causes the retreating or opening lead roller to leave contact with the conduit 104, the roller is pulled away from the conduit 104 and the material (eg, fluid, gas, paste) in the conduit 104 is removed. Etc.) is sucked backwards for at least a moment. This results in repetitive anomalies or periodic variations in the function relating material discharge to angular displacement of the pump roller support.

Accordingly, aspects of the present invention disclosed herein are systems and methodologies that readily take into account such periodic variations to accurately transfer a selected amount of material (eg, fluid material) using a rotary peristaltic pump. About. In certain aspects, for example, the present invention provides a control system configured to transfer an amount of material (eg, fluid volume) corresponding to a pump angular rotation or rotation increment equal to an integral multiple of the angular distance between adjacent rollers. . Various representative angular distances are schematically illustrated in FIGS. More specifically, FIG. 2A schematically shows a roller support 200 that supports two rollers 202 arranged at an angular distance θ of 180 °, and FIG. 2B is arranged so that θ is equal to 120 °. A roller support 200 supporting three rollers 202 is schematically shown, and FIG. 2C schematically shows a roller support 200 supporting four rollers 202 arranged so that θ is equal to 90 °. Essentially any angular distance is optionally utilized. For example, the minimum dispensing amount can be reduced by increasing the number of pump rollers. The angle θ is given by
θ = S / r
Here, S is a distance along the circumference of a circular path arranged between the rotation axes of the adjacent rollers 202 (that is, the arc length defined by the angle θ), and r is the rotation axis of the roller support 200 from the roller 202. The distance to the rotation axis. Thus, the method and system described herein eliminates roller opening as a source of variation in dispensing / suction volume between dispensing / suctions by generating the same roller opening event for each dispensing / suction. Guaranteed to do.

  To further illustrate aspects of the present invention, FIG. 3 schematically illustrates a material transfer system according to one embodiment of the present invention. In general, the material transfer system of the present invention is highly automated so that material transfer can be performed at higher throughput in addition to greater accuracy and simplicity than many existing systems. As shown, the material transfer system 300 includes a peristaltic pump 302 (eg, a multi-channel low volume peristaltic pump) mounted on a mounting component 304 (shown as a grid frame). The material transfer system 300 also includes a feedback component with a drive motor 306 that includes a position encoder and gear reducer and is operably connected to the peristaltic pump 302 for the rotatable roller support of the peristaltic pump 302. Have a precisely controlled rotation. The feedback component also includes a control system (not shown in FIG. 3) for the drive motor 306 that can provide position feedback control.

  Material conduit 308 is disposed between the compression surface and the roller of peristaltic pump 302. Also, one end set of material conduit 308 communicates with the same or different material source (not shown) and the other end set is operatively connected to material conduit support head 310 via tip 311. . The material conduit support head 310 is attached to the arm 318 via a Z-axis linear motion component 312 (e.g., a compact, high speed, short-distance travel Z-axis motion component system). Arm 318 suspends material conduit support head 310 above target holder 314. Typically, a motor (not shown) such as a solenoid motor is operably connected to the Z-axis linear motion component 312 and relative to a material site (eg, multiwell plate, membrane, etc.) located on the subject holder 314. The material conduit support head 310 is translated in the Z axis. The object holder 314 is operably connected to an X / Y axis linear motion table 320 that moves the object holder 314 relative to the material conduit support head 310 along the X and Y axes. X / Y axis linear motion table 320 is also mounted on mounting component 304. Generally, one or more motors (eg, solenoid motors, etc.) are operably connected to the material transfer system of the present invention to move the subject holder on the X / Y axis linear motion table. For example, the solenoid motor 316 moves the object holder 314 in the material transfer system 300. Although not shown in FIG. 3, the material transfer system 300 generally also includes a control drive for, for example, an X / Y axis linear motion table 320 and a position feedback for the drive motor 306. A typical control drive is shown schematically in FIG. Typically, the material transfer system of the present invention also includes a controller (also not shown in FIG. 3) configured to rotate the peristaltic pump roller support by selected rotation increments. Typically, the rotation increment substantially corresponds to an integer multiple of the angular distance between adjacent rollers supported by the roller support, thereby taking into account the periodic variations described herein. These and other aspects of the invention are described in detail below.

III. Peristaltic pumps One of the advantages of the systems and methods described herein is that the same rotational increments provide a substantially (ie, almost or strictly) uniform amount of material (eg, material volume) at the material site or material. It is to be transferred from the site. In addition, rotation increments are typically determined in certain existing systems, such as Chemnitz US Pat. No. 6,393,338, “APPARATUS AND CONTROL METHOD FOR ACCURATE ROPERY PERISTALIC PUMP FILLING” (May 2002). Unlike the devices described in the 12th issue), there is no compensation for the flow characteristics of the particular system used. Thus, the systems and methods of the present invention are typically easier and less complex to implement than many of these existing methods and systems.

  Essentially any rotary peristaltic pump can be used in the system of the present invention. Typically, a peristaltic pump uses a turning mechanism, such as a tube or other that is compressed in contact with pump rollers, shoes, etc. at several points so that each rotational movement moves material through the tube. Move material through the conduit. Typically, peristaltic pumps are configured to reversibly transfer an amount of material to or from selected material sites (eg, microtiter plates, substrate surfaces, etc.). In general, peristaltic pumps support at least two rollers (ie 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30 or more rollers). A rotatable roller carrier or support is provided. In certain embodiments, the roller support can be replaced with, for example, a roller support having a different number of rollers. Further, for example, typically the roller support supports from about 2 to about 50 rollers, more typically from about 3 to about 40 rollers, and even more typically from about 4 to about 30 rollers. To do. In general, the greater the number of rollers supported by a given roller support, the less material the peristaltic pump can transfer. This is because the controller of the present invention is typically configured to rotate the roller support by rotational increments substantially corresponding to an integer multiple of the angular distance between adjacent rollers supported on the roller support.

  In general, adjacent rollers supported by a roller support are arranged at most 180 ° apart from each other. Furthermore, the angular distance between adjacent roller pairs typically supported by a roller support is substantially (i.e., almost or exactly) of each other. For example, an adjacent roller supported by a roller support may have a rotation increment of, for example, about 12 ° (eg, corresponding to 30 rollers that are substantially equally spaced), or about 18 ° (eg, 20 rollers that are substantially equally spaced) ), About 22.5 ° (e.g. corresponding to 16 substantially equally spaced rollers), about 24 ° (e.g. corresponding to 15 substantially equally spaced rollers), about 25.7 ° (e.g. For example, corresponding to substantially 14 equally spaced rollers), about 27.7 ° (for example, corresponding to 13 substantially equally spaced rollers), about 30 ° (for example, substantially 12 equally spaced 12 rollers) Roller), about 32.7 ° (e.g. corresponding to 11 rollers at substantially equal intervals), about 36 ° (e.g. corresponding to 10 rollers at substantially equal intervals), about 40 ° (e.g. substantially 9 equally spaced rollers), approximately 45 ° (eg substantially 8 at regular intervals), about 51.4 ° (eg, 7 rollers at substantially equal intervals), about 60 ° (eg, 6 rollers at substantially equal intervals), about 72 ° (Eg, substantially five equally spaced rollers), about 90 ° (eg, substantially four equally spaced rollers), about 120 ° (eg, substantially three equally spaced rollers), about 180 ° It is optionally arranged to substantially correspond to an angular displacement selected from, for example, (e.g., two rollers at substantially equal intervals). Optionally, the angular distance between adjacent roller pairs supported by a given roller support is not equal to each other.

  Although other volumes of fluid material can be transferred using the system described herein, generally the rotation increment corresponds to at least about 0.1 μl volume of fluid material. In general, for example, fluid material is transferred to and / or from a high density multiwell plate, such as a 1536-well plate, typically having a total volume of about 10 to about 15 μl / well by the system of the present invention. For transport, microliter capacity is desirable. Larger volumes of fluid material (eg, milliliter volumes, liter volumes, etc.) are also optionally transferred using the system of the present invention. Typically, the user selects the number of rollers supported by the roller support of the peristaltic pump, the selected rotation increment, the inner cross-sectional dimensions of the material conduit used (eg diameter), when the roller presses the material conduit against the peristaltic pump compression surface By varying parameters such as the depth or degree of contact between the roller and the material conduit, the desired amount of material (eg, volume or aliquot of fluid material) transferred by the system of the present invention can be selected.

  In one embodiment, for example, the peristaltic pump comprises a multi-channel peristaltic pump that can transfer multiple quantities of material simultaneously. For example, FIG. 4 schematically shows a detailed perspective view of peristaltic pump 302 in material transfer system 300. In the embodiment shown, peristaltic pump 302 comprises five channels 400. Optionally, additional channels 400 are added to peristaltic pump 302 or one or more of channels 400 are removed from peristaltic pump 302. Typically, the number of channels is selected based on the type of material site utilized in a particular application. For example, the number of channels can be selected corresponding to a given number of rows or stages of wells in a multi-well plate. The roller support roller 402 of the peristaltic pump 302 is also shown schematically in FIG.

A rotatable roller that rotates relative to the roller support (eg, passively or actively rotatable) is typically utilized in the system of the present invention, but cannot function as a fixed roller or shoe, etc. Equivalent components are also optionally used. However, in general, rotatable rollers have less wear on material conduits (eg flexible tubing, etc.) than non-rotatable equivalents for equivalent usage. Typically, conduit wear is first observed primarily at or near the initial contact area between the roller and the conduit. To illustrate this type of wear, FIG. 5 is a cross-sectional view of a roller support or carrier 500 that supports a passively rotatable roller 502 as the roller support 500 rotates the roller 502 and contacts the material conduit 504. Is shown schematically. Arrow 506 represents the angular velocity ω _C of roller carrier 500 and arrow 508 represents the direction of material transfer through material conduit 504. A wear region 510 is shown proximate to the initial contact region between the roller 502 and the material conduit 504 in the direction of rotation of the illustrated roller support 500. For example, if a roller carrier or support is rotating at the speed V _C, passively rotatable roller support which is supported by a roller support generally has a roller speed V _R, to zero before contacting the conduit equal. Roller in contact with the conduit, typically is rotatable roller instantly by friction accelerates from _V R = 0 to _V R ₌ -V C _cosθ. Derivation of V _R = −V _C cos θ will be described later. In general, this acceleration is too large to achieve. Instead, typically the roller skids on a conduit that causes wear at or near the initial contact area 510, such as the wear area 510 shown schematically in FIG. To further illustrate, FIG. 6 schematically illustrates a roller carrier arm 600 that supports a passively rotatable roller 602 as the rotatable roller 602 contacts the material conduit 604. As described above, V _R = −V _C cos θ with respect to FIG. 6 is derived as follows:
V _R = −V _C sinφ
φ = 180 ° -90 ° -θ or 90 ° -θ
Therefore,
V _R = −V _C sin (90 ° −θ)
V _R = −V _C (sin 90 ° cos θ−cos 90 ° sin θ)
Since sin90 ° = 1 and cos90 ° = 0,
V _R = −V _C cos θ
And cos θ is 1 when the conduit is wound around the roller. Therefore, in order to wear of this type of conduit to a minimum, in certain embodiments of the present invention to actively rotate the roller optionally as initial velocity of the rollers is substantially equal to -V _C. In some of these aspects, for example, the planetary gear transmission causes such rotation of the roller, which is in the opposite or opposite direction to the rotation of the roller support. In particular, a spur gear or the like is coaxially attached to each roller. The gear pitch curve is substantially equal to the radius of the roller. A fixed ring gear surrounds the spur gear. The transmission is driven by rotating a roller support or carrier. For example, FIG. 7 schematically shows a front view of a portion of a roller support that supports an actively rotatable roller. As shown, roller support 700 supports roller 702. As also shown, as the roller 702 when the roller support 700 is rotated via the drive shaft 708 rotates at substantially -V _C by a gear transmission, spur gear 704 on each roller 702 Mounted coaxially, ring gear 706 surrounds spur gear 704.

Over time, more gradual wear is also commonly observed at all points of contact along a particular conduit. As will be described later, typically the roller is removed from the material conduit without, for example, attaching or carrying significant fluid material to the surface of the material conduit proximate to the dispensing end (eg, dispensing tip, nozzle, etc.) of the material conduit. Accelerated and decelerated to a speed sufficient to cleanly transfer material. If the force due to acceleration is greater than the frictional force between the roller and the conduit, the material conduit will wear as the roller and conduit surfaces slide against each other. The more gradual wear may also minimized by equalizing the initial velocity of the rollers -V _C by, for example, the above-described gear transmission mechanism.

  Typically, peristaltic pumps used in the system of the present invention generate a material transfer rate or flow rate sufficient to provide non-contact material distribution from the end at least proximate to the end of the material conduit. Non-contact dispensing minimizes the risk of cross-contaminating material sites such as wells located in multi-well plates. In addition, typically non-contact material distribution also transfers material “on-the-fly” from the material conduit, for example when distributing material while moving the material conduit and material site relative to each other. System throughput is improved.

  To transfer a uniform sized amount of material (eg, a uniform volume of fluid material in the range of about 0.1 to about 10 μl), for example, on the outer surface of the material conduit proximate to the dispensing end Carrying away, sticking or wicking of material at the surface must be avoided. For example, FIG. 8 schematically shows a cross-sectional view of the wicking or attachment of a volume of fluid material 800 to the tip of material conduit 802. Typically, such material wicking occurs when a certain amount of material is being transferred from the conduit at a transfer rate that is too low to prevent the material from adhering to the outer surface of the conduit. Thus, optionally, the peristaltic pump of the present invention "throws off" a selected amount of specific material being transferred from the end of the material conduit without material wicking on the outer surface of the end of the material conduit. , Configured to slow down to a rate sufficient to release or eliminate. For example, FIG. 9 is a graph schematically showing the velocity curve of a conduit tip according to one aspect of the present invention (the vertical axis is velocity V and the horizontal axis is time t). More specifically, FIG. 9 shows a generalized type of steep deceleration 900 that is used to release an aliquot of material from a conduit without causing material wicking. To further illustrate, FIG. 10 schematically illustrates a cross-sectional view of a volume of fluid 1000 being dispensed from the tip of material conduit 1002 without fluid wicking. For example, in certain embodiments, the moment of inertia of the roller support is minimized to prevent a certain amount of material from adhering to the exterior of the material conduit when the peristaltic pump flows material through the material conduit. The moment of inertia can be minimized, for example, by minimizing the weight of the roller support. Also, the system controller is typically configured to decelerate the peristaltic pump drive motor to a speed sufficient to prevent material wicking. The drive motor will be described later.

Peristaltic pumps that can be adapted for use in the system of the present invention are described, for example, by ABO Industries Inc. (San Diego, CA, USA), Analox Instruments Ltd. (London, UK), ASF Thomas Industries GmbH (Puchheim, Germany), Barant Co. (Barrington, IL, USA), Cole-Parmer Instrument Company (Vernon Hills, IL, USA), Fluid Metering Inc. (Syosset, NY, USA), Gorman-Rup Industries (Bellville, OH, USA), I & J Fisnar Inc. (Fair Lawn, NJ, USA), Moller Feinchanik GmbH & Co. (Fulda, Germany), PerkinElmer Instruments (Shelton, CT, USA), Terra Universal Inc. (Anaheim, CA, USA). Further details on rotary pumps are described, for example, in Karassik et al. (Eds.), Pump Handbook , The McGraw-Hill Companies (2000), and Nelik, Centrifugal and Rotary Pumps: FundamentalsPrice: FundamentalsCip. And both of them are used.

IV. Motion Control Typically, the motion control system of the present invention includes combined components such as a controller, motor drive, motor, encoder and resolver, user interface and software. The controller, user interface, and software will be described in detail later. In general, the drive motor of a peristaltic pump comprises at least one position encoder and at least one gear reduction component. Typical motors used in the system of the present invention typically include, for example, a servo motor and a stepping motor. In certain aspects, the feedback component of the system of the present invention includes at least one drive mechanism operably connected to the motor. Typically, the drive mechanism includes at least one control component that provides position feedback control of the motor.

  As described above, the movement of the roller support of the peristaltic pump is typically performed by a motor operably connected to the pump. Typical motors optionally used in the system of the present invention include DC servo motors (eg, brushless or gear motor type), AC servo motors (eg, induction or gear motor type), stepping motors, linear motors, and the like. . Servo motors typically have an output shaft that can be positioned by sending a coded signal to the motor. As the input to the motor changes, the angular position of the output shaft also changes. In general, a stepping motor uses a magnetic field to move a rotor. Typically this stepping can be performed in full steps, half steps or other partial step increments. A voltage is applied to the poles around the rotor. This voltage changes the polarity of each pole, and the rotor is moved by the magnetic interaction obtained between the pole and the rotor. To further illustrate, FIG. 11 schematically shows a detailed perspective view of the drive motor 306 including the position encoder and gear reduction in the material transfer system of FIG.

  In general, the system of the present invention also includes a motor drive (eg, AC motor drive, DC motor drive, servo drive, stepper drive, etc.) that functions as an interface between the controller and the motor. In certain aspects, the motor drive includes an integrated motion control function. For example, a servo drive typically provides an electrical drive output to a servo motor in a closed loop motion control system to optimize position and velocity accuracy with position feedback and correction signals. A servo drive with integrated motion control circuitry and / or software that accepts feedback provides compensation and correction signals to optimize position, velocity and acceleration. FIG. 12 schematically illustrates an X-axis and Y-axis linear motion table and a position feedback control drive device 1200 according to one aspect of the present invention. The X / Y axis linear motion table will be described in detail later.

Generally suitable motors and motor drives are described in, for example, Yaskawa Electric America, Inc. (Waukegan, IL, USA), AMK Drives & Controls, Inc. (Richmond, VA, USA), Enprotech Automation Services (Ann Arbor, MI, USA), Aerotech, Inc. (Pittsburgh, PA, USA), Quicksilver Controls, Inc. (Covina, CA, USA), NC Servo Technology Corp. (Westland, MI, USA), HD Systems Inc. (Hauppauge, NY, USA), ISL Products International, Ltd. (Syosset, NY, USA) and many other merchandise suppliers. Further details regarding motors and motor drives can be found in, for example, Polka, Motors and Drives , ISA (2002) and Hendershot et al., Design of Brushless Permanent-Magnet Motors , Magna Physics, 94 Incorporate.

V. Positioning and Mounting Components In certain aspects, the material transfer system of the present invention further includes a positioning component operably connected to the controller. The controller will be described in detail later. Generally, the positioning component has a structure in which material conduits and / or material sites are movably arranged relative to one another. Typically, the positioning component includes at least one target holder that is structured to support a material site (eg, multi-well plate, substrate, etc.). In addition, the controller typically is at or out of the material site in synchronism with the relative movement of the material conduits and / or material sites, eg, to perform high-throughput “on the fly” material distribution. The roller support is rotated to move a predetermined volume of material and the material conduit and / or material site are movably arranged relative to each other.

  For positioning along two different axes, the subject holder of the present invention generally comprises one or more alignment members arranged to receive each of the two axes of the multi-well container, for example. For example, FIG. 13 shows a detailed perspective view of the object holder 314 in the material transfer system 300 of FIG. As shown, the container station 1300 is disposed on the support structure 1302 of the object holder 314. Support structure 1302 supports vacuum plate 1304. The protrusions 1306 and 1308 function as alignment members. In the illustrated embodiment of the container station 1300, there are two x-axis protrusions 1308 and one y-axis protrusion 1306 extending from the support structure 1302. Therefore, the x-axis protrusion 1308 and the y-axis protrusion 1306 are fixedly arranged with respect to the vacuum plate 1304, and in this aspect, this places the multiwell container in place once the multiwell container is in place. Function to hold. The X-axis positioning protrusion 1308 is configured to cooperate with the x-axis surface of the multiwell container (eg, the y-axis wall of the microtiter plate), and the y-axis protrusion 1306 is configured to interact with the y-axis surface of the container (eg, the y-axis of the microtiter plate). Configured to cooperate with the shaft wall).

  The alignment member can be, for example, a locating pin, tab, ridge, recess, or wall surface. In a preferred embodiment, the alignment member includes a curved surface that contacts a suitably placed multi-well container. The use of a curved surface minimizes the bumpy effect on the container surface that contacts the alignment member, for example. As shown in FIG. 13, using two alignment members along one axis and using one alignment member along the second axis can result in surface irregularities on proper positioning of the container. Is another approach to minimizing Because the multiwell container contacts three points along the surface of the container, proper alignment does not depend on the entire regular container surface.

  In particular, certain aspects of the invention apply to the positioning of microtiter plates when used as material sites. For example, a microtiter plate 1400 is shown in FIGS. As shown, the microtiter plate 1400 includes a well region 1402 having a number of individual sample wells for holding samples and reagents. Microtiter plates are available in a variety of sample well configurations, including commonly available plates with 6, 12, 24, 48, 96, 192, 384, 768, 1536 or more wells. Microtiter plates are available, for example, from Greiner America Corp. (Lake Mary, FL, USA), Nalge Nunc International (Rochester, NY, USA), and the like. The microtiter plate 1400 has an outer wall 1404 with a registration edge 1406 at the bottom. The microtiter plate 1400 also includes a bottom surface 1408 below the well region on the bottom side of the plate. The bottom surface 1408 is separated from the outer wall 1404 by the alignment member receiving area 1410. The alignment member receiving area 1410 is limited by the surface of the outer wall 1404 and the inner wall 1412 at the end of the bottom surface 1408. The alignment member receiving area 1410 may be provided with several lateral supports 1414, but generally these alignment member receiving areas are open between the inner wall 1412 and the inner surface of the outer wall 1404.

  In accordance with the present invention, the container station alignment member is optionally arranged to cooperate with the microtiter plate inner wall 1412 to position the microtiter plate. It is advantageous to use the inner wall 1412 because the inner wall 1412 is typically more accurately formed and more closely joined around the sample well region than the outer wall of the plate 1400, such as the wall 1404. Accordingly, it is generally preferable to align the inner wall (eg, inner wall 1412) of the microtiter with respect to the alignment member, rather than aligning with an outer wall such as wall 1404. The improved positioning accuracy obtained by using the inner wall as the alignment surface allows the use of high density microtiter plates such as 1536-well plates. Further, by coordinating alignment members (eg, alignment protrusions 1306 and 1308) with the inner wall 1412 of the plate 1400, only minimal structure is required adjacent to the outside of the plate. In this way, a robot arm or other moving device can easily approach the plate 1400. By disposing the protruding portion adjacent to the inner wall 1412, the position of the plate 1400 can be easily changed. However, it can also be seen that the alignment members or protrusions can be placed in different positions to further facilitate accurate positioning of the plate.

  In general, the subject holder of the present invention includes one or more movable members. The movable member has a function of moving the container in contact with one or more alignment members. For example, once the multi-well container has been placed at a general location on the alignment member, the movable member (referred to herein as a “pusher”) causes the alignment surface of the container to contact one or more of the alignment members of the positioning device. Move the container to The positioning device can comprise a pusher for positioning the container along one or more axes. For example, often the positioning device comprises one or more pushers that position the container along the x-axis and one or more other pushers that position the container along the y-axis. The pusher can be moved by means known to those skilled in the art. For moving the pusher to move the container to a desired position, for example, an air cylinder, a spring, a piston, an elastic member, an electromagnet or other magnet, a gear drive, or a combination thereof is suitable.

  FIG. 13 shows one embodiment of a subject holder container station with a pusher to position the microtiter plate along both the x and y axes. Generally, when the microtiter plate is positioned adjacent to the X-axis and Y-axis protrusions, the bottom surface of the microtiter plate is just above the top surface 1310 of the vacuum plate 1304. A Y-axis pusher 1312 extending through the slot 1314 of the support structure 1302 is used to apply pressure to the y-axis side wall of the microtiter plate. Sufficient force is applied to the plate to press the microtiter plate against the y-axis protrusion 1306. When the microtiter plate is pressed against the y-axis protrusion 1306, an x-axis pusher 1318 extending through the slot 1320 of the support structure 1302 is used to move the x-axis wall of the microtiter plate in the direction of the x-axis protrusion 1308. Press. Thus, the microtiter plate is accurately and precisely positioned with respect to both the x-axis protrusion and the y-axis protrusion. Often, but not necessarily, it is advantageous to have one or more of the pushers contact the inner wall rather than the outer wall of the microtiter plate. In this configuration, the alignment member and pusher are under the microtiter plate. In this way, there are no protrusions in the area surrounding the outside of the plate that can otherwise interfere with other devices that, for example, place the microtiter plate on the support.

  As described above, the embodiment of the subject holder shown in FIG. 13 includes a vacuum plate 1304, which functions as a holding device that holds a properly positioned container in a desired position. Both a y-axis pusher 1312 and an x-axis pusher 1318 that provide sufficient force to accurately place the microtiter plate cause a vacuum source (not shown) to evacuate the vacuum opening or hole 1324 via the vacuum line 1322. Apply. An air source (not shown) applies air pressure through an air line (not shown) to move the pusher.

  In certain aspects, the positioning component also includes an X / Y axis linear motion table operatively connected to a position feedback control drive that controls movement of the X / Y axis linear motion table along the X and Y axes. Including. In a particular aspect, the linear motion table is configured to move only along one axis, such as the X or Y axis. Typically, the object holder is mounted on, for example, an X / Y axis linear motion table. As an example, FIG. 3 schematically illustrates a target holder 314 mounted on an X / Y axis linear motion table 320. In general, the positioning component also includes a Z-axis linear motion component with a material conduit support head (see, eg, material conduit support head 310 schematically illustrated in FIG. 3), the material conduit support head supporting a portion of the material conduit. And move along the Z-axis. Generally, the Z-axis linear motion component includes a solenoid motor or the like to move the material conduit support head along the z-axis. As described herein, the positioning component is typically configured to move the material conduit support head at a rate sufficient to eliminate adherent material deposited on the exterior of the material conduit. In certain aspects, the Z-axis linear motion component also comprises a material removal head mounted, for example, proximate to the material conduit support head. For example, certain material removal heads are configured to non-invasively remove material from the wells of a multi-well plate, for example to perform plate cleaning during certain applications. Typically, the material removal head is structured to prevent cross-contamination between the wells of the multi-well plate as material is removed from the plate. For further details regarding material removal heads, systems and related methods that are optionally adapted for use in the system of the present invention, see US Provisional Patent Application No. 60 / 461,638 by Micklash II et al., Titled “MATERIAL REMOVAL DEVICES,” "SYSTEMS, AND METHODS" (filed April 8, 2003), incorporated herein by reference.

  Various other positioning components or parts thereof can be utilized in the system of the present invention. In certain embodiments, for example, a detectable signal generated at a material site (eg, multi-well plate, substrate surface, etc.) located on a target holder of the system described herein is detected. In some of these embodiments, an opening through the subject holder is provided to facilitate this detection. To further illustrate, the subject holder optionally comprises a nest that can position a multi-well plate or other material site in certain embodiments of the invention. These and other types of subject holders that can be used in the system of the present invention are described in, for example, International Publication No. WO 01/96880, Mainquist et al. Application 60 / 492,586, titled “MULTI-WELL CONTAINER POSITIONING DEVICES AND RELATED SYSTEMS AND METHODS” (filed Aug. 4, 2003), US Provisional Patent Application 60 / 492,629 by Evans et al., “ NON-PRESSURE BASED FLUID TRANSFER IN ASSAY DETECTION SYSTEMS AND RELATED "METHODS" (filed Aug. 4, 2003), each incorporated herein by reference.

  In certain aspects, the material transfer system further comprises at least one attachment component that attaches at least the peristaltic pump, the feedback component, and the positioning component to each other. Typically, the mounting component is substantially rigid and is manufactured, for example, from steel or other material that can adequately support other system components during system operation.

VI. Cleaning component Optionally, the material transfer system of the present invention also comprises a cleaning component that is configured to clean the material conduit (e.g., its tip), e.g., when the positioning component moves the material conduit at least in the vicinity of the cleaning component. Have As discussed above, for example, as fluid material is dispensed, some fluid typically wicks up the outer surface of the material conduit tip. This generally causes further wicking if the adherent fluid has not been removed from the chip. This is because as the chip surface finish is covered with fluid, it tends to attract more fluid, for example during the next dispensing step. Furthermore, typically this results in an inaccurate amount of material being dispensed. This is because the wicked material is not distributed to selected material sites and / or distributed to unselected sites. This inaccuracy can be increased when multiple amounts of material are dispensed simultaneously from multiple material conduits. This is because material wicking tends to occur at different rates in the material conduit tip. Thus, generally wicked material is cleaned from the tip of the material conduit, for example, by using the cleaning component of certain aspects of the invention during the dispensing process.

In certain aspects, for example, the cleaning component includes a vacuum chamber with at least one opening. In or near the opening, the positioning component moves the material conduit and removes wicked or otherwise adherent material from the outer surface of the material conduit by an applied vacuum. Typically, the outer cross-sectional dimension of the material conduit is smaller than the cross-sectional dimension of the opening. For example, FIG. 15A schematically illustrates a partially transparent perspective view of a vacuum chamber 1502 of a cleaning component 1500 according to one aspect of the present invention. As shown, a plurality of openings 1504 are provided in the cleaning component 1500 and are typically in communication with an outlet 1506 operably connected to a vacuum source (not shown). A material conduit support head 1508 is also disposed on the cleaning component 1500. The opening 1504 is in the material conduit tip 1510 of the material conduit support head 1508 so that the material conduit tip 1510 can be at least partially lowered into the opening 1504 and the adherent material can be removed from the material conduit tip 1510 under application of a vacuum. It has a corresponding structure. FIG. 15B schematically shows a detailed cross-sectional view of a material conduit tip 1510 disposed near the opening 1504. Arrow 1512 represents the velocity _VA of air flowing through opening 1504. As the material conduit tip 1510 is lowered into the opening 1504, the area of the opening 1504 decreases, thereby increasing the _VA in the remaining gap between the vacuum chamber 1502 and the material conduit tip 1510. Pull or otherwise remove the adhesive material from the outer surface of 1510. Optionally, for example, a vacuum chamber is placed on the surface of the target holder of the positioning component of the system of the present invention.

As the cross-sectional dimension of the vacuum chamber opening decreases, the risk of contacting the vacuum chamber when lowering the chip into the opening, and hence the risk of damaging the material conduit chip, is reduced. Accordingly, an opening in a vacuum chamber having an opening cross-sectional dimension that is too large to generate a _VA large enough to remove adhesive material from the material conduit tip when the material conduit tip is disposed in the opening. A conformable material such as a specific tape is optionally placed on the part. This tape functions to seal the opening. In these embodiments, the tape is pierced when the chip is lowered, typically making a hole slightly larger than the cross-sectional dimension of the chip. _A sufficiently large _VA is typically achieved in the gap between the tip and the hole edge of the tape to remove the adhesive material from the outer surface of the tip.

VII. Material Conduit The material conduit used in the system of the present invention includes various embodiments. In some embodiments, for example, the end of the material conduit includes a tip (eg, a tapered tip such as a nozzle) that is manufactured integrally with the conduit or connected to the conduit, eg, via an insert. In general, the size of the material conduit (eg, pump tubing, etc.) and / or the tip used (eg, the inner cross-sectional dimension) depends at least in part on, for example, the desired dispensing volume, the viscosity of the material being transferred, etc. Although larger sizes are optionally utilized, the cavity disposed through the material conduit and / or tip is typically about 100 μm to about 10 ⁵ mm, more typically about 500 μm to about 10 ⁴ mm, Even more typically, it has a cross-sectional dimension of about 1 mm to about 10 ³ mm. Optionally, the cavity disposed through the material conduit or tip includes at least two different cross-sectional dimensions. In certain aspects, the cavities disposed through the material conduit and / or the tip include different cross-sectional dimensions. In general, the optimal tubing size (eg, inner diameter) is large enough to deliver the dispensing volume fast enough to generate a large speed at the dispensing tip, but with hysteresis and other mechanical / hydraulic variations It is small enough so that the angular displacement of the pump is large enough to make it vague. As explained here, once a fairly high tip speed is reached, a fluid or other material is drained away enough to allow dispensing without entering the target well of the multi-well container, for example using a dispensing tip. it can. By moving the target material site or tip along the x and y axes in synchrony with the pump delivery timing, an automated system is created to quickly and accurately distribute fluid to the material sites. The pump and the X / Y axis linear motion table have been described in detail above. Further, when the number of pump channels and delivery chips is increased to 2, 4, 8, 16, etc., the number of delivery is correspondingly reduced to 1/2, 1/4, 1/8, 1/16, etc., respectively.

  To further illustrate, there are many cases of distributing delicate live cells to multi-well plates or other material sites. These cells can be damaged by shear forces associated with receiving force through a delivery tip with a very small inner diameter (eg, less than 200 μm). If the tip inner diameter used for dispensing these cells is so large that a large tip speed cannot be achieved, the fluid can form drops on the tip rather than forming a flow during the dispensing cycle. Material wicking has also been described above. In one aspect of the present invention, the tip is further moved down into the selected well along the Z axis such that after dispensing the fluid, the fluid level in the well is slightly above the end of the delivery tip. Thus, accurate distribution is achieved. This also allows fluid to be dispensed into wells having a smaller cross-sectional area than, for example, fluid drops that can be formed on a chip under non-contact dispensing conditions. When dispensing is complete, a wet touch-off condition is created that raises the tip along the Z-axis and / or lowers the material site to remove residual drops from formation on the delivery tip. Optionally, the tip contacts, for example, the dry side of the well to wick-off the droplet.

  In certain aspects, the system of the present invention is configured to propel droplets formed at the end of the dispensing tip without using mechanical inertia principles. In this configuration, fluid is dispensed to form droplets at the end of the dispensing tip. At this point, the pump typically stops flowing material into the material conduit, and the dispensing tip typically moves along the Z axis to accelerate the drop without moving or significantly deforming the drop. It is accelerated at a sufficient speed downward. Once the appropriate speed is reached, the dispensing tip is rapidly decelerated to propel the droplet away from the end of the dispensing tip. Typically, the moving droplet shape is more cylindrical than the original droplet formed on the chip and has a smaller diameter. This allows, for example, droplets to enter wells with a small cross-sectional area. This approach provides another non-contact dispensing method.

In one aspect, the system of the present invention generates a negative pressure pulse after generating an initial positive pressure pulse, as described herein. Negative pressure pulses are generated by large negative flow rate changes that occur at the end of a given dispensing cycle to prevent droplets from forming on the chip. More specifically, the dispensing volume is generally small and typically the volume dispensed at a low rate is minimized so that typically a large flow rate is achieved in a short time at the beginning of a particular dispensing cycle. Is done. Typically, large negative flow rate changes occur when large flow rates are suddenly stopped. These sudden flow velocity changes or pressure pulses are transmitted from the pump to the dispensing tip outlet as efficiently as possible without compromising dispensing performance. In general, the flow path downstream of the pump roller support should not have any features that impart an accumulator or flow restriction characteristic to the fluid system. In some embodiments, for example, the flow path has the following characteristics:
1. Minimum capacity between pump and dispensing tip;
2. Maximum tubing stiffness (eg, 1/16 inch outer diameter fluorinated ethylene propylene (FEP) tubing) and minimum length of peristaltic tubing on the outlet side of the pump;
3. Optimized tubing connector or insert for connecting peristaltic / FEP and FEP / distribution tip joints. A typical fitting has the following characteristics:
(I) greater rigidity than tubing and tips;
(Ii) constant internal cross-sectional dimensions with smooth walls;
(Iii) similar internal cross-sectional dimensions for tubing, tips and inserts; and (iv) a compliant seal;
4). Tubing should be straight to within about 60 mm from the outlet of the dispensing tip.

  For example, FIGS. 16A-D schematically illustrate various material conduit tips according to certain aspects of the invention. More specifically, FIG. 16A schematically shows a pump tubing 1600 and a dispensing tip 1602 that are connected to each other by being inserted into an insert 1604. O-ring 1606 attaches pump tubing 1600 and dispensing tip 1602 to insert 1604. FIG. 16B schematically shows pump tubing 1600 and dispensing tip 1602 connected together by being inserted into an insert 1608 (shown as a compliant sleeve). FIG. 16C schematically shows an insert 1610 inserted into the pump tubing 1600 and the dispensing tip 1602 to connect the pump tubing 1600 and the dispensing tip 1602 together. Typically, the insert 1610 is more rigid than the pump tubing 1600 or the dispensing tip 1602. FIG. 16D schematically shows a pump tubing 1600 manufactured with an integral dispensing tip.

Material conduits, tips, and inserts are optionally manufactured from a wide variety of materials. Typical materials used to make material conduits include fluorinated ethylene propylene (FEP), polytetrafluoroethylene (PTFE), perfluoroalkoxy (PFA), autoprene, C-FLEX® (silicone). Styrene-ethylene-butylene (SEBS) modified block copolymer with oil), NORPRENE® (polypropylene based material), PHARMED® (polypropylene based material), silicon, TYGON (Registered trademark), VITON (registered trademark) (including various fluoropolymer elastomers), and the like. Material conduit tips and inserts are, for example, polytetrafluoroethylene (TEFLON ^™ ), polypropylene, polystyrene, polysulfone, polyethylene, polymethylpentene, polydimethylsiloxane (PDMS), polycarbonate, polyvinyl chloride (PVC), polymethyl methacrylate (PMMA). ) And other polymer materials. Material conduit tips and inserts are also optionally made from other materials, including glass and various metals. Typically, materials for making material conduits, tips and inserts are described in, for example, Saint-Gobain Performance Plastics (Garden Grove, CA, USA), DuPont Dow Elastomers L. L. C. (Wilmington, DE, USA) and many others are readily available from a variety of commodity suppliers.

VIII. Material Site The system and method of the present invention can be adapted for use with essentially any type of material site. Typical material sites used in the system of the present invention include material containers, substrate surfaces, and the like. Exemplary material containers include multi-well material containers such as microwell plates, reaction blocks, and other containers that are used, for example, to perform multiple assays, synthesis reactions, or other processes in parallel. . Such multi-well material containers generally comprise, for example, 6, 12, 24, 48, 96, 192, 384, 768, 1536 or more wells and are generally described in, for example, Greiner America Corp. (Lake Mary, FL, USA), Nalge Nunc International (Rochester, NY, USA), H + P Labortechnik AG (Oberschleibheim, Germany) and others. Further details regarding reaction blocks suitable for use in the system of the present invention are described, for example, in International Publication No. WO 03/020426, titled “PARALLEL REACTION DEVICES” (filed Sep. 5, 2002) by Micklash II et al. And is incorporated here.

To further illustrate, optionally the system of the present invention is also configured to dispense material onto the substrate surface. For example, the system described herein can be used to generate dot arrays at a variety of different densities on a substrate surface. Commonly arranged materials are used, for example, in clinical tests (eg, blood cholesterol test, blood glucose test, pregnancy test, ovulation test, etc.) in addition to other uses known in the art. Essentially any substrate material can be optionally adapted for use with the system of the present invention. In certain embodiments, for example, the substrate is made from silicon, glass, or a polymeric material (eg, glass or polymer microscope slides, silicon wafers, etc.). Suitable glass or polymer substrates, including microscope slides, are available from a variety of commercial suppliers such as Fisher Scientific (Pittsburgh, PA, USA). Optionally, the substrate used in the system of the present invention is a film. Suitable membrane materials include, for example, polyaramid membranes, polycarbonate membranes, porous plastic matrix membranes (eg POREX® porous plastic), porous metal matrix membranes, polyethylene membranes, poly (vinylidene difluoride) membranes, Polyamide membrane, nylon membrane, ceramic membrane, polyester membrane, polytetrafluoroethylene (TEFLON ^™ ) membrane, woven mesh membrane, microfiltration membrane, nanofiltration membrane, ultrafiltration membrane, dialysis membrane, composite membrane, hydrophilic membrane, hydrophobic Membrane, polymer-based membrane, non-polymer-based membrane, powdered activated carbon membrane, polypropylene membrane, glass fiber membrane, glass membrane, nitrocellulose membrane, cellulose membrane, cellulose nitrate membrane, cellulose acetate membrane, polysulfone membrane, Suitable from polyethersulfone membrane, polyolefin membrane, etc. It is selected. Many of these membrane materials are P.I. J. et al. Covert Associates, Inc. (St. Louis, MO, USA) and Millipore Corporation (Bedford, MA, USA).

IX. Controllers, computer program products, and additional system components Generally, the controller of the automated system of the present invention is substantially identical from the material conduit for each material transfer to minimize periodic variations in material transfer. It is configured to open the roller. Typically, the controller includes a motor (eg, via a motor drive), a positioning component (eg, X / Y axis linear motion table, Z axis motion component, etc.), cleaning component, detector, fluid sensor, robotic movement device, etc. Are operatively connected to and control the operation of these components. More specifically, the controller is typically included as a separate or integral system component, for example, for rotation of the roller support in selected rotation increments, movement of the positioning component, and detectable signal received from the sample container. It is used for performing detection and / or analysis by the detector of the above. Optionally, the controller and / or other system components are connected to a suitably programmed processor, computer, digital device, or other logic device or information equipment (eg, analog to digital or digital to analog converter as appropriate). The function directs the operation of these devices according to pre-programmed or user entered commands (eg material conduit cross-sectional dimensions, rotation increments, transfer capacity, etc.) and receives data and information from these devices Interpret, manipulate, and report this information to the user.

  Optionally, the controller or computer includes a monitor, which is often a cathode ray tube (“CRT”) display, a flat panel display (eg, active matrix liquid crystal display, liquid crystal display, etc.), and the like. Often computer circuitry is placed in a box containing many integrated circuit chips, such as a microprocessor, memory, interface circuitry, and the like. This box also optionally includes a hard disk drive, floppy disk drive, high capacity removable drive such as a writable CD-ROM, and other common peripheral elements. Optionally, input devices such as a keyboard and mouse provide input from the user. A typical system including a computer is schematically illustrated in FIG.

  Typically, a computer is in the form of user input to a set of parameter fields (eg, GUI) or in the form of pre-programmed instructions (eg, pre-programmed for a variety of different specific operations). Including appropriate software for receiving user instructions. The software then translates these instructions into the appropriate language to command the operation of one or more controllers, changing or selecting the desired operation, eg, speed or mode of various system components, moving positioning components Etc. are executed. The computer can then receive data from, for example, sensors / detectors contained within the system, interpret the data, and be understood by the user, for example, according to programming in monitoring detectable signal strength, positioning of multi-well containers, etc. Provide in format or use that data to initiate another controller instruction.

  More specifically, the software generally used to control the operation of the system of the present invention directs the system to transfer material (eg, fluid material) to the material site, for example, and the container is on the subject holder. It includes logic instructions such as instructing the target holder of the positioning component to push the container into contact with the alignment member when in position and / or instructing the robot handling device to move the container. To further illustrate, the present invention provides: (i) a rotation increment substantially corresponding to an integer multiple of the angular distance between adjacent rollers supported by the roller support of a peristaltic pump; (ii) a cross-sectional dimension of the material conduit; (iii) For receiving one or more input parameters selected from the group consisting of: the amount of material transferred to or from the material site; and (iv) the angular distance between adjacent rollers supported by the roller support of the peristaltic pump. A control software having one or more logical instructions, or a computer program product including a computer readable medium is provided. Software such that when one or more material conduits are operably connected to a peristaltic pump and the peristaltic pump transfers material through the material conduit, an amount of material corresponding to the incremental rotation is transferred to or from the material site. Alternatively, the computer program product may also include one or more logical instructions for rotating the peristaltic pump roller support in rotational increments substantially corresponding to an integral multiple of the angular distance between adjacent rollers supported by the peristaltic pump roller support. including. In certain aspects, the software or computer program product further includes at least one logic instruction to move the X / Y axis linear motion table and the Z axis motion component in synchronization with the rotation of the roller support. For example, the computer readable medium of the computer program product may be one or more of a CD-ROM, floppy disk, tape, flash memory device or component, system memory device or component, hard drive, data signal embedded in a carrier wave, etc. Optionally included.

The computer may be, for example, PC ^{(DOS TM,} OS2 TM of Intel x86 or Pentium ^{chip-compatible, WINDOWS TM, WINDOWS NT TM,} WINDOWS95 TM, WINDOWS98 TM, WINDOWS2000 TM, WINDOWS XP TM, LINUX based machine, MACINTOSH ^TM, Power PC, Alternatively, it can be a UNIX-based (eg, SUN ^TM workstation) machine or other commercially available computer known to those skilled in the art. Word processor software (for example, Microsoft Word ^™ or Corel WordPerfect ^™ ) or database software (for example, spreadsheet software such as Microsoft Excel ^™ , Corel Quattro Pro ^™ or standard desktop program such as Microsoft Access ^™ or Paradox ^™ such as Microsoft desktop ^TM ) It can also be adapted to the present invention. Software for performing material transfer to selected wells of multi-well plates, assay detection, and data deconvolution using standard programming languages such as Visual Basic, C, C ++, Fortran, Basic, Java, etc. Optionally constructed by those skilled in the art.

  Optionally, the automated system of the present invention further detects and quantifies light absorbance, transmission, and / or luminescence (eg, luminescence, fluorescence, etc.) and / or in a well of a multi-well container or on a substrate surface or It is configured to detect and quantify changes in their properties of samples arranged at other material sites. Alternatively, or simultaneously, including chemical signals (eg, pH, ionic state, etc.), heat (eg, to monitor endothermic or exothermic reactions using a temperature sensor) or other suitable physical phenomena Any of a variety of other signals from well containers or other material sites can be quantified by the detector. In addition to the other system components described herein, the material transfer system of the present invention also optionally includes an illumination or electromagnetic radiation source, optics, and a detector. The systems and methods of the present invention are flexible and allow assays of essentially any chemistry so that they can be used at all stages of assay development, including prototyping and mass screening.

  In one aspect, the system of the present invention is configured to perform area imaging, but can be configured for other formats, including as a scanning imager or non-imaging counting system. Typically, the area imaging system places the entire multiwell container or other sample at once on the detector plane. Therefore, it is typically not necessary to move the photomultiplier tube (PMT) or scan the laser. This is because the detector images the entire container in parallel on many small detector elements (eg, charge coupled devices (CCDs), etc.). Generally, following this parallel acquisition stage, serial processing is performed to read the entire image from the detector. Typically, a scanning imager sends a laser or other light beam over the sample, stimulating fluorescence and reflectivity at each point or line. In certain cases, confocal optics is used to minimize fluorescence from the focus. Images are generated by accumulating points or lines continuously over time. Typically, non-imaging counting systems use PMTs or photosensitive diodes to detect changes in light transmission or emission, for example, within the wells of a multi-well container. The system then typically combines the light output from each well into one data point.

  A wide variety of illumination or electromagnetic radiation sources and optics can be adapted for use in the system of the present invention. Accordingly, not all possible variations available in the system of the present invention will be described here, but they will be apparent to those skilled in the art. Typical electromagnetic radiation sources that are optionally used in the system of the present invention include, for example, lasers, laser diodes, electroluminescent devices, light emitting diodes, incandescent lamps, arc lamps, flash lamps, fluorescent lamps, and the like. A preferred type of laser used in the assay system of the present invention is an argon ion laser. A typical optical system that directs electromagnetic radiation from an electromagnetic radiation source to a sample container and / or from a multiwell container to a detector typically includes one or more to focus and / or direct the electromagnetic radiation as desired. Includes lenses and / or mirrors. Many of the optical systems also include optical fiber bundles, optical couplers, filters (eg, filter wheels, etc.) and the like.

  Suitable signal detectors optionally used in these systems detect luminescence, luminescence, transmission, fluorescence, phosphorescence, absorbance, etc. In one aspect, the detector monitors a plurality of optical signals that correspond in place to “real time” results. For example, examples of the detector or sensor include PMT, CCD, sensitized CCD, photodiode, avalanche photodiode, optical sensor, scanning detector, and the like. Optionally, each of these and other types of sensors are easily incorporated into the systems described herein. Optionally, the detector moves relative to a material site such as a multiwell plate or other assay component, or alternatively, the multiwell plate or other assay component moves relative to the detector. In certain aspects, for example, the detection component is coupled to a translation component that moves the detection component relative to a material site disposed on a container positioning device of the system described herein. Optionally, the system of the present invention includes a plurality of detectors. In these systems, typically such detectors are sensitive to the multi-well plate or other container (i.e., the detector is sensitive to the characteristics of the target plate or container or part thereof, the plate). For example, in a multi-well plate or other container, or adjacent to a multi-well plate or other container. In certain embodiments, the detector is configured to detect electromagnetic radiation emanating in the wells of the multi-well container.

Optionally, the detector includes or is operably connected to a computer, for example, the computer comprises system software for converting detector signal information into assay result information and the like. For example, optionally the detector exists as a separate device or is integrated with the controller into a single instrument. By integrating these functions into one device, it is easy to connect these devices to a computer by using only a few or one communication port to transmit information between system components. Detection components optionally included in the system of the present invention are described, for example, by Skoog et al., Principles of Instrumental Analysis , 5th Edition, Harcourt Brace College Publishers (1998) and Curlell, Analytical Institute. , Inc. (2000), both of which are incorporated herein by reference.

  Optionally, the system of the present invention also includes at least one robotic movement or gripping component that grips a material site, such as a multiwell plate, between components of an automated system and / or the system and other locations (e.g., It has a structure that can be moved to and from other work stations. In certain aspects, for example, the system further comprises a gripping component that moves the multi-well plate between positioning components, culture or storage components, and the like. The various available robot elements (robot arms, mobile platforms, etc.) can be used with these systems or can be modified for use with these systems, typically the robot elements are their motion and others Is operatively connected to a controller that controls the function of the. Exemplary robotic gripping devices optionally adapted for use in the system of the present invention are described in, for example, Downs et al. US Pat. No. 6,592,324, entitled “GRIPPER MECHANSIM” (issued July 15, 2003). ) And Downs et al., International Publication No. WO 02/068157, entitled “GRIPPPING MECHANSIMS, APPARATUS, AND METHODS” (filed Feb. 26, 2002), both of which are incorporated herein by reference.

  FIG. 17 schematically illustrates a representative example of a material removal system including information equipment that can incorporate various aspects of the present invention. One skilled in the art will appreciate that the present invention is optionally implemented in hardware and software. In certain aspects, different aspects of the invention are implemented in client-side logic or server-side logic. As will also be appreciated in the art, the present invention or its components may be incorporated into a media program component (eg, a fixed media component), which is stored in a suitably configured computing device. Contains logic instructions and / or data that, when loaded, cause the device or system to execute in accordance with the present invention. As further understood in the art, fixed media containing logical instructions can also be sent to viewers on fixed media for physical loading on the viewer's computer or include logical instructions. Fixed media may reside on a remote server for viewers to access and download program components via communication media.

  FIG. 17 illustrates an information appliance or digital device 1700 that can be understood as a logical device (eg, a computer or the like), which can read instructions from the media 1717 and / or the network port 1719, and the network port 1719 reads the fixed media 1722. The server 1720 may optionally be connected. Information appliance 1700 can then instruct the server or client logic using those instructions to embody aspects of the invention, as understood in the art. One type of logical device that can embody the invention is the computer system shown at 1700, which includes a CPU 1707, optional input devices 1709 and 1711, a disk drive 1715, and an optional monitor 1705. Fixed medium 1717 or fixed medium 1722 beyond port 1719 can be used to program such a system and can be disk-type optical or magnetic media, magnetic tape, solid dynamic or static memory, and the like. In certain embodiments, aspects of the invention can be implemented in whole or in part as software recorded on this fixed medium. A typical computer program product has been described above. Communication port 1719 can also be used to initially receive instructions used to program such a system, and can be any type of communication connection. Optionally, aspects of the present invention may be implemented in whole or in part in an application specific integrated circuit (ACIS) or programmable logic device (PLD) circuit. In such cases, aspects of the present invention may also be implemented in a computer understandable description language that can be used to generate an ASIC or PLD. FIG. 17 also includes a material transfer system 300 that is operatively connected to information equipment 1700 via server 1720. Optionally, material transfer system 300 is directly connected to information equipment 1700. In operation, the material transfer system 300 typically transfers material to and / or from selected material sites on the positioning component of the material transfer system 300, for example as part of an assay or other process. FIG. 17 also shows a detector 1724, which is optionally included in the system of the present invention. As shown, detector 1724 is operatively connected to information appliance 1700 via server 1720. In certain aspects, detector 1724 is directly connected to information device 1700. In certain aspects, detector 1724 is configured to detect a detectable signal generated at a material site disposed on a positioning component of material transfer system 300. In other aspects, the material site (eg, a multi-well container) is (eg, manually or robotically) before and / or after material is transferred to and / or from the material site on the positioning component of the material transfer system 300. Forwarded to detector 1724 (using a mobile device).

X. System component manufacturing System components (eg positioning components, cleaning components, etc.) include, for example, machining, stamping, engraving, injection molding, cast molding, embossing, extrusion, etching (eg electrochemical etching, etc.) or other techniques It is optionally formed by various manufacturing techniques or combinations of these techniques. These and other suitable manufacturing techniques are generally known in the art, see, for example, Altinas, Manufacturing Automation: Metal Cutting Mechanicals, Machine Tool Vibrations, and CNC Design , Met. ), Metal Cutting and High Speed Machining , Kluwer Academic Publishers (2002), Stephenson other, Metal Cutting Theory and Practice, Marcel Dekker (1997), Rosato, Injection Mold ng Handbook, ³ rd Ed. Kluwer Academic Publishers (2000), Fundamentals of Injection Molding , W. J. et al. T.A. Associates (2000), Welan, Injection Molding of Thermoplastics Materials , Vol. 2, Chapman & Hall (1991), Fisher, Extraction of Plastics , Halted Press (1976), and Chung, Extraction of Polymers , here by Ther-Price , Hans-b. . In certain aspects, after manufacture, the system component may be a Xylan 1010DF available from a hydrophilic coating, a hydrophobic coating (eg, Whitford Corporation (West Chester, PA), for example, to prevent interaction of the component surface with reagents, samples, and the like. Further processing is optionally performed by covering the surface with / 870 Black etc.).

XI. Material Transfer Method In addition to the system and computer program product described herein, the present invention also relates to a material transfer method. For example, one method includes transferring material (eg, cell suspension, reagent, buffer, solid support suspension, etc.) through one or more material conduits of the systems described herein, where The controller has at least one rotation substantially corresponding to an integral multiple of the angular distance between adjacent rollers supported by the roller support, such that the amount of material transferred to or from the material site corresponds to the rotation increment Rotate the roller support in increments. For example, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, ... times the angular distance between adjacent rollers of a given roller support Essentially any rotation increment can be selected. As described herein, typically the controller rotates the roller support so that the shear effect on the material being transferred (eg, cells, etc.) is minimized. In general, the controller performs a substantially similar roller opening from the material conduit for each transfer of material, for example, to minimize periodic fluctuations in the transfer of material. In addition, a substantially uniform material volume is generally transferred to or from the material site with the same rotational increment. Further, the rotational increments typically used as described herein are not compensated for the flow rate characteristics of a particular system. This simplifies the implementation of the system and method of the present invention compared to many existing approaches.

  In some embodiments, material is transferred to the material site (ie, non-contact material distribution) without the material conduit contacting the material site. For example, these methods allow the controller to apply a negative pressure pulse near the end of the material conduit after the roller support has been rotated by a selected number of rotation increments, for example, so that a certain amount of material does not adhere to the outer portion of the material conduit. Optionally including adding. Optionally, the method includes moving the material conduit at a rate sufficient to eliminate the adherent material attached to the outer portion of the material conduit, eg, transferring the material to the material site, or outside the material conduit. Clean the part. In some embodiments, the method contacts the adherent material attached to the outer portion of the material conduit with another object (such as the end of a well of a multi-well container) to remove the adherent material from the outer portion of the material conduit. Including doing.

  The material sites described herein optionally include multi-well containers (eg, microtiter plates). In these aspects, the material transfer method transfers a first quantity of material to a first well of a multi-well container, such that the multi-well container communicates with a second well of the multi-well container, for example, a positioning component Optionally moving the material conduit and / or the multi-well container relative to each other, transferring a second quantity of material to the second well of the multi-well container, and so on. Typically, the transfer and transfer steps are performed substantially simultaneously, for example to “fly” and perform material distribution.

  Another method of the invention involves transferring material through the material conduit such that a quantity of material adheres to the distal portion of the material conduit to form a quantity of deposited material. Thereafter, generally these methods also accelerate at least the end portion of the material conduit in the direction of the material site such that a certain amount of deposited material is transferred (eg, excluded) from the end portion of the material conduit to the material site, and Including slowing down.

Essentially any biochemical or cellular assay or synthesis reaction can be adapted for execution by the methods of the invention and in the system. To further illustrate, common types of assays performed, for example, in multi-well plates, include signal transduction, cell adhesion, apoptosis, cell migration, GPCR, cell permeability, acceptance among many others known in the art. Includes body / ligand binding, intracellular calcium flux, membrane potential, nucleic acid hybridization, cell growth / proliferation. For further details on these and other assays involving multi-well plates, see, for example, Parker et al. (2000) “Development of high throughput screening aiding fluorsence-alignment-polarization: J. et al. Biomolecular Screening 5 (2): 77-88 , Asa (2001) "Automating cell permeability assays", Screeing 1: 36-37, Norrington ( 1999) , "Automation of the drug discovery process", Innovations in Pharmaceutical Technology 1 (2 ) : 34-39, Fukushima et al. (2001) "Induction of reduced enderative permeability to hormone peroxidase by factor and s of human astrocyclades and circadians. ells: detection in multi-well plate culture ", Methods Cell Sci. 23 (4): 211-9, Neumayer (1998) "Fluorescence ELISA, a comparison between two fluorgenic and one chromogenic enzyme subs ent", BPI 10 (Nr. 5) -Adenine dinucleotide phosphate with nanomolar sensitivity ", Biochem J. et al . 367 (Pt1): 163-8, Rogers et al. (2002) “Fluorescence detection of plant extracts that affect neuronal voltage-gate Ca ²⁺ channels”, Eur. J. et. Pharm. Sci. 15 (4): 321-30, and Rappaport et al. (2002) “New perfluorocarbon system for multi-row of anchorage-dependent dependent cells”, Biotechnique 1 To do. Further details regarding various methods optionally performed using the system of the present invention can be found in, e.g., U.S. Patent Application No. 60 / 492,629 by Evans et al., Entitled "NON-PRESSURE BASED FLUID TRANSFER IN ASSETY DETECTION SYSTEM AND RELATED METHODS". "(Filed Aug. 4, 2003), incorporated herein by reference.

XII. EXAMPLES The examples and aspects described herein are for illustrative purposes only, and various modifications or alterations will be suggested to those skilled in the art, which are within the spirit and scope of this application and the scope of the claims. You can see that

  This example shows various distributions using an 8-chip system. In this system, the peristaltic pump was equipped with a roller support that supported 12 rollers and the angular distance between each pair of adjacent rollers was 30 °. FIG. 18A shows a series of distributions in a system set at an angular displacement of 12 ° per distribution. As shown, it is clear that there was a repetitive pattern of changing distribution capacity. In fact, some distribution volumes were essentially zero. FIG. 18B shows a series of distributions in the system set at an angular displacement of 18 ° per distribution. There was no zero volume distribution, but periodic fluctuations in the distribution volume were still observed. FIG. 18C shows a series of distributions in the system set at an angular displacement of 30 ° per distribution. As shown, there was essentially no variation in distribution capacity at this angular displacement setting. Since the angular distance between each pair of adjacent rollers was 30 ° in this system, rotation increments that are typically integer multiples of 30 ° are optimal for this system. FIG. 18D shows a series of distributions in the system set at an angular displacement of 42 ° per distribution. Although the rate of variation between dispenses was expected to be smaller due to the higher dispense volume, a close examination of the droplet size again indicates that there was periodic variation.

  Although the foregoing invention has been described in some detail for purposes of clarity and understanding, it will be apparent to those skilled in the art from reading the present disclosure that various changes and details in form may be made without departing from the scope of the invention. . For example, all the techniques and apparatus described above can be used in various combinations. All publications, patents, patent applications and / or other references cited in this application are for any purpose, as if each indicates that each of them is individually incorporated for any purpose. The entirety of which is incorporated herein by reference.

1A and 1B schematically illustrate a peristaltic pump roller opening event. 2A-C schematically illustrate various representative angular distances. 1 schematically illustrates a perspective view of a material transfer system according to one aspect of the present invention. Figure 4 schematically shows a detailed perspective view of a peristaltic pump from the material transfer system of Figure 3; FIG. 2 schematically shows a cross-sectional view of a roller support that passively supports a rotatable roller as the roller support rotates the roller into contact with the material conduit. 1 schematically shows a passively rotatable roller in contact with a material conduit. FIG. 2 schematically shows a front view of a portion of a roller support that supports an actively rotatable roller. FIG. 3 schematically shows a cross-sectional view of a fixed volume of wicking fluid or fluid attached to a tip of a conduit. 4 is a graph schematically illustrating a velocity curve of a conduit tip according to an aspect of the present invention. FIG. 3 schematically shows a cross-sectional view of a volume of fluid being dispensed from a tip of a conduit where no wicking fluid is present. Fig. 4 schematically shows a detailed perspective view of a drive motor with a position encoder and a gear reduction part in the material transfer system of Fig. 3; 1 schematically shows an X-axis and Y-axis linear motion table and a position feedback control drive unit according to an aspect of the present invention. Fig. 4 schematically shows a detailed perspective view of a target holder of the material transfer system of Fig. 3; FIG. 14A schematically shows a top view of a microtiter plate. FIG. 14B schematically shows a bottom view of the microtiter plate shown in FIG. 14A. FIG. 14C schematically shows a cross-sectional view of the microtiter plate shown in FIG. 14A. FIG. 15A schematically illustrates a partially transparent perspective view of a vacuum chamber of a cleaning component according to one aspect of the present invention. FIG. 15B schematically shows a detailed cross-sectional view of a material conduit tip positioned near a portion of the opening of the vacuum chamber of FIG. 15A. 16A-D schematically illustrate various material conduit tips according to certain aspects of the present invention. FIG. 17 is a block diagram illustrating a representative example logic device that may incorporate various aspects of the present invention. FIG. 18A shows the fluid volume dispensed from the system when the rotation increment was 12 ° per dispense volume. FIG. 18B shows the fluid volume dispensed from the system when the rotation increment was 18 ° per dispense volume. FIG. 18C shows the fluid volume dispensed from the system when the rotation increment was 30 ° per dispense volume. FIG. 18D shows the fluid volume dispensed from the system when the rotation increment was 42 ° per dispense volume.

Explanation of symbols

100, 200 Roller support 102, 202 Roller 104 Conduit 300 Material transfer system

Claims (96)

At least one peristaltic pump having a rotatable roller support supporting at least two rollers;
At least one motor operably connected to the peristaltic pump to rotate the roller support; and at least one controller operably connected to the motor, wherein one or more material conduits are operable to the peristaltic pump When connected and the peristaltic pump transports material through the material conduit, an adjoining supported by a roller support so that an amount of material corresponding to the rotation increment is transported to or from at least one material site A controller configured to rotate at least the roller support by at least one rotation increment substantially corresponding to an integral multiple of the angular distance between the rollers;
A material transfer system comprising:   The material transfer system of claim 1, wherein the same rotation increment causes a substantially uniform amount of material to be transferred to or from the material site.   The material transfer system of claim 1, wherein the rotation increment is not compensated for the flow rate characteristics of the system.   The at least one detector operably connected to the controller, further comprising a detector configured to detect a detectable signal generated at one or more material sites. Material transfer system.   The material transfer system of claim 1, further comprising at least one material conduit operably connected to the peristaltic pump.   6. The controller of claim 5, wherein the controller is configured to perform substantially the same roller opening from a material conduit for each material transfer to minimize periodic fluctuations in material transfer. Material transfer system.   The at least one positioning component operably connected to the controller further comprising a positioning component configured to movably position at least one material conduit and / or one or more material sites relative to one another. The material transfer system described.   8. The material transfer system of claim 7, wherein the positioning component comprises at least one object holder having a structure that supports the material site.   The material transfer system of claim 7, further comprising a material conduit operably connected to the positioning component and the peristaltic pump.   At least one cleaning component operably connected to the controller, wherein the material conduit is operably connected to at least the positioning component and the positioning component moves the material conduit at least proximate to the cleaning component; The material transfer system of claim 7, further comprising a cleaning component having a structure for cleaning.   The material transfer system of claim 7, further comprising at least one attachment component that attaches at least the peristaltic pump, the motor, and the positioning component to each other. At least one material conduit;
At least one peristaltic pump operably connected to the material conduit, the peristaltic pump comprising a rotatable roller support supporting at least two rollers;
At least one feedback component operably connected to the peristaltic pump, the feedback component comprising at least one motor for rotating the roller support; and at least one controller operably connected to the feedback component; Substantially equal to an integral multiple of the angular distance between adjacent rollers supported by the roller support so that the amount of material transferred through the material conduit to or from at least one material site corresponds to a rotation increment A controller configured to rotate at least the roller support by at least one rotation increment corresponding to
Material transfer system with   The material transfer system of claim 12, wherein the material transfer system is automated.   13. The material transfer system comprises a plurality of material conduits, at least two of the material conduits being spaced apart from each other by a distance such that they communicate simultaneously with different wells of at least one multi-well container. The material transfer system described.   The material transfer system of claim 12, wherein the material transfer system comprises a plurality of material conduits, two or more of the material conduits being in communication with different material sources. 13. A material transfer system according to claim 12, wherein the cross-sectional dimension of the cavity disposed through the material conduit is between ^{1 [} mu] m and ¹⁰ < ⁵ > [mu] m.   13. The material transfer system of claim 12, wherein the peristaltic pump generates a material flow rate sufficient at least near the end to effect non-contact material distribution from the end of the material conduit.   The material transfer system of claim 12, wherein the peristaltic pump comprises a multi-channel peristaltic pump.   The material transfer system of claim 12, wherein the peristaltic pump is configured to reversibly transfer an amount of material to or from the material site.   13. Material transfer according to claim 12, wherein the roller support supports 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30 or more rollers. system.   The material transfer system of claim 12, wherein the roller support is replaceable with at least one other roller support.   13. The material transfer system of claim 12, wherein when the peristaltic pump flows material through the material conduit, the moment of inertia of the roller support is minimized to prevent a certain amount of material from sticking to the exterior of the material conduit. .   The material transfer system of claim 12, wherein the angular distance between pairs of adjacent rollers supported by the roller support is substantially equal to each other.   13. A material transfer system according to claim 12, wherein adjacent rollers supported by the roller support are arranged at a maximum 180 degrees apart from each other.   The material transfer system of claim 12, wherein the feedback component comprises at least one drive mechanism operably connected to the motor, the drive mechanism comprising at least one control component that provides position feedback control of the motor.   The material transfer system of claim 12, wherein the feedback component further comprises one or more scales operably connected to the controller, wherein the scales detect the weight of the material disposed at the one or more material sites. .   The material transfer system of claim 12, wherein the motor comprises at least one position encoder and at least one gear reduction component.   The material transfer system according to claim 12, wherein the motor comprises a servo motor or a stepping motor.   13. The controller of claim 12, wherein the controller is configured to perform substantially the same roller opening from a material conduit for each material transfer to minimize periodic fluctuations in material transfer. Material transfer system.   13. A material transfer system according to claim 12, wherein the rotation increment corresponds to a material volume of at least 0.1 [mu] l.   13. A material transfer system according to claim 12, wherein the same rotation increment transfers a substantially uniform amount of material to or from the material site.   The material transfer system of claim 12, wherein the rotation increment is not compensated for flow rate characteristics of the system.   The at least one detector operably connected to the controller, further comprising a detector configured to detect a detectable signal generated at one or more material sites. Material transfer system.   The material transfer system of claim 12, wherein the roller is rotatable.   35. The material transfer system of claim 34, wherein the peristaltic pump comprises a gear mechanism that rotates a rotatable roller when the motor rotates a roller support.   35. The material transfer system of claim 34, wherein the controller is further configured to rotate at least one of the rollers supported by the roller support.   37. The material transfer system of claim 36, wherein the roller rotates in a direction opposite to the direction of rotation of the roller support to minimize material conduit wear.   37. The material transfer system of claim 36, wherein the roller and roller support rotate at substantially equal absolute speeds.   The controller provides at least one negative pressure pulse at least near the end of the material conduit after rotating the roller support by rotational increments to prevent a certain amount of material from adhering to the exterior of the material conduit The material transfer system according to claim 12.   40. The material transfer system of claim 39, further wherein the moment of inertia of the roller support is minimized to prevent a certain amount of material from adhering to the exterior of the material conduit.   The material transfer system of claim 12, wherein at least one end of the material conduit includes at least one tip.   42. A material transfer system according to claim 41, wherein the tip is integrated into the distal end.   42. The material transfer system of claim 41, wherein the cavity disposed through the tip has at least two different cross-sectional dimensions.   42. The material transfer system of claim 41, wherein at least a portion of the tip is tapered.   42. The material transfer system of claim 41, wherein at least a portion of the material conduit proximate the distal end is substantially straight.   46. The material transfer system of claim 45, wherein the length of the substantially straight portion of the material conduit is at least 60 mm.   46. The material transfer system of claim 45, wherein an end of a material conduit and the tip are connected by an insert.   48. The material transfer system of claim 47, wherein a portion of the insert is inserted into a portion of the end and a portion of the tip.   48. The material transfer system of claim 47, wherein a portion of the end and a portion of the tip are inserted into a portion of the insert.   48. The material transfer system of claim 47, wherein the insert is made from a material that is at least less flexible than the material conduit.   The material transfer system of claim 12, wherein the material site includes at least one material container and / or at least one substrate surface.   52. The material transfer system of claim 51, wherein the material container comprises a multi-well material container having 6, 12, 24, 48, 96, 192, 384, 768, 1536 or more wells.   52. The material transfer system according to claim 51, wherein the substrate surface comprises a film surface.   13. The material transfer system of claim 12, further comprising at least one positioning component operably connected to the controller, the positioning component having a structure that movably positions material conduits and / or material sites relative to each other. .   55. The material transfer system of claim 54, wherein the positioning component comprises at least one object holder structured to support the material site.   The controller rotates the roller support so that a certain amount of material is transferred to or from the material site in synchronism with the relative movement of the material conduit and / or material site, and the material conduit and / or material. 55. The material transfer system of claim 54, wherein the material transfer system is configured to simultaneously position sites movably together.   The positioning component comprises at least one X / Y axis linear motion table operably connected to at least one position feedback control drive, the position feedback control drive being in X / Y axis along the X and Y axes. 55. The material transfer system of claim 54, wherein the material transfer system controls movement of a linear motion table.   58. The material transfer system of claim 57, wherein the positioning component comprises at least one object holder operably connected to an X / Y axis linear motion table, the object holder having a structure for supporting a material site.   55. The positioning component comprises at least one Z-axis linear motion component having at least one material conduit support head, the material conduit support head supporting at least a portion of the material conduit and moving along the Z-axis. Or the material transfer system of 58.   60. The material transfer system of claim 59, wherein the positioning component is configured to move the material conduit support head at a speed sufficient to eliminate adherent material deposited outside the material conduit.   60. The material transfer system of claim 59, wherein the Z-axis linear motion component includes at least one solenoid.   60. The material transfer system of claim 59, wherein the material conduit comprises a plurality of material conduits and the material conduit support head supports one or more portions of each of the at least two material conduits.   64. The material of claim 62, wherein the portion comprises a distal portion of a material conduit, the distal portions being spaced from one another by a distance such that they are simultaneously substantially in communication with different wells in at least one multi-well container. Transport system.   64. The material transfer system of claim 63, wherein the end portion is substantially straight.   65. A material transfer system according to claim 64, wherein the length of at least one of the substantially straight end portions is at least 60 mm.   64. The material transfer system of claim 63, wherein each end portion of the material conduit has at least one tip.   68. The material transfer system of claim 66, wherein the cavity disposed through the tip has at least two different cross-sectional dimensions.   68. The material transfer system of claim 66, wherein at least a portion of the tip is tapered.   69. The material transfer system of claim 68, wherein at least one of the material conduits and the corresponding at least one tip are substantially connected by an insert.   70. The material transfer system of claim 69, wherein a portion of the insert is inserted into a portion of the material conduit and a corresponding portion of the tip.   70. The material transfer system of claim 69, wherein a portion of the material conduit and a portion of the corresponding tip are inserted into a portion of the insert.   70. The material transfer system of claim 69, wherein the insert is made from a material that is at least less flexible than the material conduit.   The cleaning component further comprising: at least one cleaning component operably connected to the controller, the cleaning component having a structure for cleaning the material conduit when the positioning component moves the material conduit at least proximate to the cleaning component. 54. The material transfer system according to 54.   The cleaning component includes a vacuum chamber having at least one opening, and the positioning component includes a material in or near the opening to remove the adherent material from the outer surface of the material conduit by the applied vacuum. 75. The material transfer system of claim 73, wherein the material transfer system moves the conduit.   75. The material transfer system of claim 74, wherein the outer cross-sectional dimension of the material conduit is smaller than the cross-sectional dimension of the opening.   55. The material transfer system of claim 54, further comprising at least one attachment component that attaches at least the peristaltic pump, the feedback component, and the positioning component to each other.   77. The material transfer system of claim 76, wherein the mounting component is substantially rigid. (I) a rotation increment substantially corresponding to an integral multiple of the angular distance between adjacent rollers supported by the roller support of the peristaltic pump;
(Ii) the cross-sectional dimensions of the material conduit;
(Iii) the amount of material transferred to or from the material site; and (iv) the angular distance between adjacent rollers supported by the roller support of the peristaltic pump;
A material corresponding to a rotation increment to receive one or more input parameters selected from the group consisting of: and when one or more material conduits are operatively connected to the peristaltic pump and the peristaltic pump transfers material through the material conduits Peristate in increments of rotation substantially corresponding to an integral multiple of the angular distance between adjacent rollers supported by the peristaltic pump roller support such that the amount of is transferred to or from at least one material site To rotate the roller support of the pump,
A computer program product comprising a computer readable medium having one or more logical instructions.   The computer program product of claim 1, further comprising at least one logic instruction for moving the X / Y axis linear motion table and the Z axis motion component in synchronization with rotating the roller support. Providing a material transfer system with at least one controller operably connected to at least one motor, the motor being operatively connected to at least one peristaltic pump with a rotatable roller support Said roller support supporting at least two rollers and operably connected to at least one material conduit; and transferring material through the material conduit, to at least one material site or The controller by at least one rotation increment substantially corresponding to an integral multiple of the angular distance between adjacent rollers supported by the roller support such that the amount of material transferred from at least one material site corresponds to the rotation increment. Including the step of rotating the roller support Fee transfer method.   81. The method of claim 80, wherein the material is selected from the group consisting of a cell suspension, a reagent, a buffer, and a solid support suspension.   81. The method of claim 80, wherein the controller rotates the roller support such that shear effects on the transfer material in the material are minimized.   81. The method of claim 80, wherein the material is transferred to the material site without contacting the material conduit to the material site.   In order to prevent a certain amount of material from sticking to the outside of the material conduit, the controller applies at least one negative pressure pulse at least near the end of the material conduit after rotating the roller support by rotational increments. 81. The method of claim 80, further comprising:   81. The method of claim 80, further comprising moving the material conduit at a rate sufficient to remove any adherent material deposited outside the material conduit.   81. The method of claim 80, further comprising contacting adhesive material, if any, attached to the exterior of the material conduit with at least one other object to remove the adhesive material from the exterior of the material conduit. . The material site includes at least one multi-well container, the method comprising:
Transferring at least a first amount of material to at least a first well of a multi-well container;
Moving the material conduit and / or the material site relative to each other such that the material conduit is in communication with at least a second well of the multiwell container; and at least a second amount of material in the second of the multiwell container. 81. The method of claim 80, comprising the step of transferring to a well of the same.   90. The method of claim 87, wherein the moving and at least one transferring step are performed substantially simultaneously.   88. The method of claim 87, wherein the moving step comprises disposing a portion of a material conduit above or in the second well.   81. The system of claim 80, wherein the system includes a plurality of material conduits operably connected to a peristaltic pump, and the method includes transferring a plurality of amounts of material to or from the material sites via the material conduits. The method described.   94. The method of claim 90, wherein the plurality of amounts of material are transferred substantially simultaneously.   The material site includes at least one multi-well container, and the ends of the at least two material conduits are spaced apart by a distance corresponding to the distance between at least two wells disposed in the multi-well container; 94. The method of claim 90, comprising simultaneously transferring material to or from the two wells via the two material conduits. At least one material conduit;
At least one pump operably connected to the material conduit for transferring material through the material conduit;
At least one positioning component operably connected to the material conduit and moving the material conduit; and at least one controller operably connected to the pump and the positioning component, wherein the pump is fed with material via the material conduit. Providing a material transfer system with a controller for transferring and moving the material conduit to the positioning component;
Transferring the material through the material conduit such that a quantity of material adheres to the end portion of the material conduit to form a predetermined amount of adherent material;
Accelerating at least the distal portion of the material conduit by the positioning component in the direction of the material site; and the distal portion of the material conduit by the positioning component such that a predetermined amount of adherent material is transferred from the distal portion of the material conduit to the material site. A method of transferring material to a material site, comprising the step of slowing down.   94. The method of claim 93, wherein the deceleration step comprises removing an amount of adherent material from the end portion of the material conduit.   94. The method of claim 93, wherein a predetermined amount of adherent material is transferred to the material site without contacting the material conduit end portion and the material site. 94. The method of claim 93, wherein the material comprises a cell suspension to minimize shear effects on the cells to be transferred.