DESC:TECHNICAL FIELD

Embodiments of the present disclosure are related, in general to pipetting, and more particularly, but not exclusively to a method and system for perform pipetting, calibration of the pipette, mixing of the samples, centrifugation and nitrogen evaporator.

BACKGROUND

In clinical trials the collected samples from the human participant will be processed as per the standards. Before inserting the samples in the HPLC the samples need multiple processing to separate the plasma from the samples. This work flow consists pipetting and mixing of the solutions with the help of pipette and vortex mixer and to separate the plasma centrifuge and nitrogen evaporator will be used one or more time based on the standard operation procedure.

All the above-mentioned process needs to be carried with high precision and accuracy, Operations like pipetting is repetitive motion and every stage require loading and unloading of the vials which is not only a time-consuming process and prone to human error.

To address the above-mentioned issues the automation is mandatory, automation of the process not only reduce the process time also decrease human error with high accuracy. The entire system is modular so the user can perform only one or more specific operation instead of running the whole system.

BRIEF DESCRIPTION OF DRAWINGS

The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate exemplary embodiments and, together with the description, serve to explain the disclosed principles. In the figures, the left-most digit(s) of a reference number identifies the figure in which the reference number first appears. The same numbers are used throughout the figures to reference like features and components. Some embodiments of device or system and/or methods in accordance with embodiments of the present subject matter are now described, by way of example only, and with reference to the accompanying figures, in which:

Figure 1 illustrates the flow diagram of the workflow of the liquid handling station

Figure 2 illustrates an assembly design of the automated liquid handling station with all operation modules

Figure 3 illustrates a concept design of the gantry robot made of aluminum extrusion to create Cartesian workspace

Figure 4 illustrates a sectional view of the centrifuge with the four shaker assembly

Figure 5 illustrates an assembly model drawing of the shaker with motor and rotary union and locking mechanism addition to that the vial arrangement also showed

Figure 6 illustrates an assembly diagram of a vial cap removing mechanism with the necessary actuators and holders which are shown in the dotted line

Figure 7 illustrates an assembly diagram of a pipetting module, with the mechanism to convert the manual pipette with the help of the servo motor and holding mechanism

Figure 8 illustrates an assembly diagram of a nitrogen evaporator with the water heater provision to dry the solvent on the RIA vial

The figures depict embodiments of the disclosure for purposes of illustration only. One skilled in the art will readily recognize from the following description that alternative embodiments of the structures and methods illustrated herein may be employed without departing from the principles of the disclosure described herein.

DETAILED DESCRIPTION

In the present document, the word "exemplary" is used herein to mean "serving as an example, instance, or illustration." Any embodiment or implementation of the present subject matter described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments.

While the disclosure is susceptible to various modifications and alternative forms, specific embodiment thereof has been shown by way of example in the drawings and will be described in detail below. It should be understood, however that it is not intended to limit the disclosure to the particular forms disclosed, but on the contrary, the disclosure is to cover all modifications, equivalents, and alternative falling within the spirit and the scope of the disclosure.

The terms “comprises”, “comprising”, or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a setup, device or method that comprises a list of components or steps does not include only those components or steps but may include other components or steps not expressly listed or inherent to such setup or device or method. In other words, one or more elements in a device or system or apparatus proceeded by “comprises… a” does not, without more constraints, preclude the existence of other elements or additional elements in the device or system or apparatus.

Embodiments of the present disclosure relates to a system for liquid handling station for handling of bio analytical samples in pharmaceutical industries. The entire workflow is explained in the flow diagram shown in Figure 1

The pre-process A is the process of the system enables an authorized person with granted access to input the batch no and time stamp of the blood sample along with the operator’s name and unique identification number. The system monitor the placing of the vials on the custom designed vial holder arrangement on the loading bay with the help of dedicated machine vision module. The system will crosscheck the manual entry of the vial loading on the user interface with the visual input from the camera. The vial arrangement is placed on the loading bay manually and the camera system provide feedback system.

From the loading bay the vial holders will be transferred to the shaker on the centrifuge with the help of 4DOF robotic arm. The pipetting process is carried with the automated pipetting module B The samples are pipetting with the help of gantry robot and pipette attached on the end effector of the gantry robot. The gantry robot has end effector as pipetting module and vial cap removal mechanism

Once the pipetting is over the shaker C will rotate at the preset rpm provided by the user to mix the samples. The robotic arm will use top cover to close the shaker and the shaker will rotate with the help of dedicated motor. The shaker will have cavity to pass the coolant so the vials can be maintained at 40C

After the mixing process pipetting process D might be carried as per the user input after that centrifuge process E will be carried, while centrifuge process the vials will be placed inclined 300 with the aid of shaker. The coolant is transferred inside the shaker to keep the samples at 40C temperature

The vial holders are transferred to the nitrogen evaporator with the help of robotic arm the vial holders for the nitrogen evaporator F are placed on a water heat bath to keep the temperature at 400C temperature. The pipe assembly made of brass pipes with nozzle is used for nitrogen passage

Figure 2 illustrates an assembly of the different modules used for various process in the automated liquid handling station.

As illustrated in Figure 2, the Automated Liquid Handling Station 100 comprises one or more components configured for fully automated process for bio analytical samples. In one embodiment, the exemplary system 100 comprises a gantry robot 101, a base 102, Shaker which can hold 96 vial arrangement 104 placed on the Centrifugation system 103, the separate location for the loading and unloading bay 105, a robotic arm 106, Nitrogen evaporator with water heater 107, end effector which has pipette holder and pipetting module and cap removal mechanism 108.

The gantry robot system 101 provide precise and fast linear movement for the pipetting and pipette calibration the base 102 hold the centrifugation 103, The certification able to rotate at 5000 rpm so the samples on the vials can will be separated due to centrifugal force. The shaker 104 is placed on the centrifugation will rotate about axis perpendicular to the rotational axis of the centrifugation. The loading and unloading bay 105 is where the operator places the vial holder assembly the robotic arm 106 used for pick and place the objects including but not limited to vial holder assembly, manual pipette 503, etc.
The gantry robot 101 system is made of the aluminium extrusion 111 for the support and linear movement. The end effector of the gantry robot 112 is the pipetting module which converts the manual pipette 503 to the automated pipetting module, Opposite to the pipetting module cap removing module 113 is used to remove the cap of the vial so the pipetting operation can be performed also for shaker operation the cap need to be re attached with the help of the same module 113. The pipetting module 112 and the cap removal mechanism 113 can be moved in the Z axis with the help of the servo motor 114 the servo motor provide the proper feedback to get the higher accuracy.

The centrifugation assembly 103 provide four shaker holder 202 and the tip assembly holder 201 the opening 203 provide the space for mounting rotary union and slip ring which provides the electrical connection and coolant for the samples. The big opening 204 is for the high speed rotary union and ring assembly. The high speed rotor can with stand 5000 rpm while the rotary union connected with the shaker can run 500 rpm. The entire centrifugation is dynamically balanced so there will be minimal vibration and wobbling on the high speed operation

The shaker assembly 300 is placed on place holders of the centrifugation on shaker holder. The gear assembly 301 for the high torque generation. The small rotary union and slip ring 302 for the shaker. The vial holder assembly 305 is placed on the shaker from the loading bay with the help of the robotic arm. The provision 304 is provided for the top cover. The top cover is required so when the shaker rotate the vials would not slip of from the position

In the gantry robot 101the end effector 114 have the cap removal mechanism 400 on the behind of the pipetting module 113. In the cap removal 400 the outer shell 401 is made of stainless meal sheet to provide the housing for the mechanism. The cap removal mechanism can be used for 5ml Ria vial and the small 2 ml HPLC vial. These vials are placed on the custom designed vial holders. The end of the cap holders are 404 two piece cylinder cut into half so the ria vial cap will be hold from the inside and the HPLC vial caps are been hold from the outside. The slits 404 are placed on the guideways 403 on the outer shell and the slits can be slide on the guideway with the help of servo motor on the servo holder 402.

The opposite to the cap removal system the pipetting module assembly 500. This module operations are to convert the manual to the automatic pipetting system. The holder 501 is sliding on the z axis with the help of sliding rod. The pipette stroke can be achieved by the linear plunger 502. A small dc motor 504 control the dial of the manual pipette 503 the dial reading is monitored by a camera as feedback. A small lever 505 is used to hold the manual pipette 503.

The nitrogen evaporator with the water heating facility 600 is placed on the unloading part of the automated liquid handling station. The close and open system 601 is used to close and the open the lid which is a made of bronze pipe assembly 603 the end of the pipes the bronze nozzles 602 is created for the diffusion of the nitrogen gas. The water bath is provided 604, the vial assembly is placed on it with the help of the robotic arm 106. The water drains 605 is provide in the at the bottom of the water bath 604 so the water can be drained manually as per the periodic maintenance procedure.

The illustrated steps are set out to explain the exemplary embodiments shown, and it should be anticipated that ongoing technological development will change the way particular functions are performed. These examples are presented herein for purposes of illustration, and not limitation. Further, the boundaries of the functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternative boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed. Alternatives (including equivalents, extensions, variations, deviations, etc., of those described herein) will be apparent to persons skilled in the relevant art(s) based on the teachings contained herein. Such alternatives fall within the scope and spirit of the disclosed embodiments. Also, the words "comprising," "having," "containing," and "including," and other similar forms are intended to be equivalent in meaning and be open ended in that an item or items following any one of these words is not meant to be an exhaustive listing of such item or items, or meant to be limited to only the listed item or items. It must also be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise.

Furthermore, one or more electronic storage media and controller may be utilized to control embodiments consistent with the present disclosure. An electronic storage media and controller refers to any type of microcontroller, microprocessor, personal computer, or any form of electronic circuit. Thus, an electronic storage media and controller may store instructions for execution by one or more processors, including instructions for causing the processor(s) to perform steps or stages consistent with the embodiments described herein. The term “electronic storage media and controller” should be understood to include tangible items and exclude carrier waves and transient signals, i.e., are non-transitory. Examples include random access memory (RAM), read-only memory (ROM), volatile memory, non-volatile memory, hard drives, CD ROMs, DVDs, flash drives, disks, and any other known physical storage media.

Finally, the language used in the specification has been principally selected for readability and instructional purposes, and it may not have been selected to delineate or circumscribe the inventive subject matter. Accordingly, the disclosure of the embodiments of the disclosure is intended to be illustrative, but not limiting, of the scope of the disclosure.

With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity.
,CLAIMS:We claim:

1. A system capable of performing pipetting, mixing solutions, and separating plasma from samples, comprising a gantry robot for pipetting, a robotic arm for transferring components, a vortex shaker for mixing samples, a nitrogen evaporator, and a centrifuge for component separation.
2. The system as claimed in claim 1, wherein the gantry robot is equipped with a cap removal mechanism and a visual feedback system enabling the automation of manual pipettes, and wherein the robot utilizes limit switches and servo motors to establish a Cartesian coordinate system, allowing pipette tip engagement and pipetting based on user input.
3. The system as claimed in claim 2, wherein the system includes a separate station and bin for storing pipette tips, both unused and used, in conjunction with the automated pipette.
4. The system as claimed in claim 2, wherein the cap removal mechanism utilizes a servo motor and mechanical links to remove round caps from vials up to 5mm in inner diameter; and wherein the mechanism employs Cartesian mapping, moving the cap removal component downward to grasp the vial cap from inside with the help of a servo motor and string, subsequently lifting it to remove the cap.
5. The system as claimed in claim 1, wherein the robotic arm employs servo motors and feedback sensors, such as tactile and pressure sensors, to detect and avoid collisions with humans or other system components; and where in the top of the robotic arm is covered with a metal sheet to prevent sample spillage and slipping.
6. The system as claimed in claim 1, wherein the shaker incorporates a cooling system with a rotary union and slip ring, enabling operation at 500 rpm without spilling and maintaining low temperature for mixed solutions; and wherein a96-well vial arrangement is placed on the shaker post-pipetting.
7. The system as claimed in claim 1, wherein the system is fully automated, necessitating minimal human intervention due to feedback sensors and surveillance systems. User input through the Human Machine Interface initiates automated processes, eliminating the need for manual guidance.
8. The system as claimed in claim 1, wherein the system is universal and compatible with samples, vials, and consumables of any make in bio-analytical laboratories.
9. The system as claimed in claim 7, wherein surveillance system collects and publishes data in real-time through Industrial Internet of Things (IIoT) technology and complies with 21CFR part 11 standards.
10. The system described in claim 1, wherein the system is deployed in the workspace equipped with the sensors and feedback modules to prevent any collision between the machine and operator or preventing any damages due to the mishandling or machine error
11. The system as claimed in claim 5, wherein the collision detection system incorporates magnetic gearbox, solenoid coils and sensors to generate magnetic flux, any intervention on the magnetic flux will result the locking of the magnetic gearbox.
12. A system as claimed in claim 2, wherein the specific end effector used in the system uses harmonic gearbox drive with hydraulic circuit incorporated with the help of mini hydraulic pump and brake to produce zero backlash and high positional accuracy