Patent Application
20190168207
A pipette is a laboratory tool commonly used in chemistry, biology and medicine to transport a measured volume of liquid, often as a fluid dispenser. Pipettes come in several designs for various purposes with differing levels of accuracy and precision, from single piece glass pipettes to more complex adjustable or electronic pipettes. Many pipette types operate by creating a partial vacuum above the liquid-holding chamber and selectively releasing this vacuum to draw up and dispense liquid, for example. Measurement accuracy varies depending on the style of pipette employed.
This disclosure relates to a pipette dispenser that utilizes an electromechanical print head to dispense a volume from a tip associated with the pipette dispenser. In contrast to conventional pipette tip dispensing, the print head when utilized as the final dispensing element on the pipette tip can dispense smaller volumes than the volume amount that can be dispensed from a conventional pipette dispenser/tip that in general is no less than 2.0 micro liters, for example. By utilizing the print head as the control mechanism to control flow from the pipette tip in controlled and precise amounts, volume levels to be dispensed can be controlled to about 0.1 nano liters, for example. The ability to accurately measure, mix, and dispense small fluid volumes is an important function in clinical and research laboratory settings. Handheld pipettes are fundamental tools used to manipulate small fluid volumes for molecular biology, immunoassays, molecular diagnostics, drug discovery, cancer research, and many other life science applications, for example. However, often current pipette technology limits precise volume control to no less than 2 micro liters.
Experiments involving precious fluids (e.g., solutions of antibodies, nucleic acids, enzymes, therapeutics, cell cultures, or samples with a short shelf-life) often involve low working concentrations. Thus, the 2 micro liter lower limit of current pipette technology often involves preparation of serial dilutions to achieve target working concentrations. Serial dilutions are time and resource intensive and are prone to variation and error. By utilizing the print head to control precise volumes distributed from the pipette dispenser, distributed volumes that are substantially below the 2.0 micro liter limit can be achieved (e.g., 0.1 nano liter +/−0.05 nL). Various pipette dispenser and tip combination examples are possible. In some cases, the tip can be manually loaded with a given volume from another collection source and subsequently mated to the pipette dispenser. The pipette dispenser then issues commands that direct the print head to dispense a commanded volume that is less than the collected volume. In another example, a collection nozzle for pipette samples can be integrated with the pipette dispenser. Collected samples from the collection nozzle can then be transferred to a reservoir on the dispenser that can then be distributed via the print head in precise amounts and in response to the commands.
Example print heads can include thermal ink jet print heads or piezoelectric print heads, for example. The fluid supplied to the tip 120 can be provided as a fluidic cartridge, in one example, that is inserted into the pipette dispenser 110 with the capability of providing suitable volumes described herein to the tip 120 containing the print head 130. The fluidic cartridges can be interchangeable, providing multiple fluids through a given print head 130. The tip 120 may also be interchangeable and autoclaved between fluids. The tip 120 can therefore be used several times for the same or different fluid and then after a pre-determined volume of fluid has passed through the tip 120, then the tip 120 can be replaced, if desired.
In one example, the tip 120 can receive the volume from another collection source (e.g., a collection pipette that collects large volume samples above 2.0 micro liters (e.g., 1.0 milliliters) other than the pipette dispenser 110. After loading, the tip 120 can be mated to the pipette dispenser 110 to dispense the amount of the volume from the print head 130 based on the command (see e.g.,
The print head 130 can be a thermal ink jet print head, for example, that dispenses a specified volume in response to the command but other print head types are possible. The pipette dispenser 110 can include a controller (see e.g.,
The apparatus 200 can be implemented as a wireless handheld device with sub-micro-liter dispensing control via the print head 230. This includes pre-programmed or user-defined dispensing protocols that can dispense single or complex mixtures. The mixtures can be premixed with diluents or directly injected. A universal serial bus (USB) interface and/or other computer interface can also be provided. The tip 270 can be implemented as 10 or 20 micro liter tips, for example, which can then be dispensed from the print head 230. Applications supported by the apparatus 200 include immunology assay development, molecular biology, molecular diagnostics, cancer research, drug discovery, quality assurance and quality control, and other biotech, biopharma, or life sciences applications, for example.
In another example, a piezo print head can be utilized as the print head 400. Piezo print heads include microscopic piezoelectric elements that are constructed behind the print nozzles. When an electrical charge is applied to them, these elements can bend backward, forcing precise amounts of volume onto the dispensing location. Since electrical charges can be turned on and off like a switch, there can be a large amount of control over the rate of dispersant being ejected through the nozzle while also creating spherical dispensing dots at different droplet sizes.
The tip 524 receives the volume from another collection source than the pipette dispenser in manual load application where the tip 524 can be mated to the pipette dispenser to dispense the amount of the volume from the print head 514 based on the command. In an alternative example, a collecting nozzle 528 can be provided that is emptied into the dispensing vessel at 524. This can include MEMs pumps or other pneumatic devices to create a vacuum to collect samples into the collecting nozzle 528 and then transfer the collected sample into the vessel at 524.
The pipette dispenser 510 can connect to an integrated MEMS chip with thermal ink jet (TIJ) nozzles and associated components as previously described. The body of the dispenser 510 can also connect to an integrated pad flex interface, for example. A plunger or button 530 at the top of the pipette body initiates fluid dispensing or dispenser ejection via mechanical motion initiated by the button. In one example, pushing the button 530 creates electrical signals that can generate a command to the print head 514 to dispense via a controller 540. In another example, pushing the button 530 down far enough mechanically disconnects the pipette 524 from the unit 510 similar to how a conventional pipette tip is disconnected from a pipette. An optional side push button to command volume ejections can be provided at 544 on the pipette dispenser 510. The controller 540 is resident in the pipette dispenser 510 and actuates nozzle firing on the MEMS chip for control of the print head 514 via the flex interface described herein.
A double ejection mechanism can be provided that includes partial actuation that ejects only fluid and full actuation that ejects the tip from the pipette body. Onboard memory (not shown) can be provided for pre-programmed or user-defined protocols, customizable applications, and system diagnostics, for example. An onboard rechargeable battery 550 can be provided for wireless functioning. Battery recharging can be provided via USB interface 554. A low voltage warning/lockout can occur when the battery 550 is low (e.g., below a predetermined threshold). A USB to computer or thumb drive interface can be provided to enable data transfer and application sharing, for example. A Bluetooth wireless connection (not shown) can be provided for communications to the controller 540. A digital user interface can be provided to select protocols or to manually define fluid volumes on-the-fly. The interface can prompt users to move through protocol steps for dispensing a given volume, for example. An onboard LED (See e.g.,
The tips 524 can have well-plate alignment mechanism for direct dispensing that should not contaminate the body TIJ head 514. This may involve a crutch or guide that matches up with common plate formats (e.g., 96, 48, or lower density well plates) or other reaction vessels. A pipette stand (not shown) can be provided that holds the pipette dispenser 510 in a fixed position with a moveable stage below where a micro-well plate or other reaction vessel may be moved into position. The pipette dispenser 510 can include user feedback to confirm correct placement before dispensing. This can also serve as docking station for computer interface and battery recharging, for example. Also, volume ejection feedback loop can be provided which reports actual fluid volume ejected for QA/QC and diagnostics. Such status can be provided via a display which can be mounted at display location 560. Other mechanisms can be provided to aspirate in precious fluids and/or diluent for streamlined use. Pipette dispenser housings may be modular to allow critical component sterilization by autoclave, for example. This may include backpressure regulation via pump or valve at the dispenser 510.
The controller 540 can include a processor that can execute instructions from a memory not shown. The processor can be a central processing unit (CPU), field programmable gate array (FPGA), or a set of logic blocks that can be defined via a hardware description language such as VHDL. The instructions can be executed out of firmware, random access memory, and/or executed as configured logic blocks, such as via registers and state machines configured in a programmable gate array, for example. The instructions can be stored on a machine-readable medium such as a memory, for example. Although a display at 560 is shown, other user feedback features can be activated such as audio instructions indicating when to dispense at a given location. As noted previously, display of potential dispensing values that can be dispensed via the print head 514 can be displayed. These values can be displayed in increments such as in a range that is less than 2.0 micro liters for example down to smaller dispensing amounts such as 0.1 micro liter, for example.
The display 560 can be located below the hand grip area such as shown at 518 to enable ambidextrous operation of the pipette dispenser 510. An optional dispense button 570 can be provided on the end of the pipette dispenser 510 to enable automatic dispensing when the pipette dispenser has achieved a desired dispensing depth with respect to a given dispensing location. The pipette dispenser 510 can be constructed out of various materials including plastic (e.g., Lexan) body construction. Metallic body construction can also be provided. Hybrid construction can include both metallic and plastic components that form the overall body construction.
What have been described above are examples. One of ordinary skill in the art will recognize that many further combinations and permutations are possible. Accordingly, this disclosure is intended to embrace all such alterations, modifications, and variations that fall within the scope of this application, including the appended claims. Additionally, where the disclosure or claims recite “a,” “an,” “a first,” or “another” element, or the equivalent thereof, it should be interpreted to include one or more than one such element, neither requiring nor excluding two or more such elements. As used herein, the term “includes” means includes but not limited to, and the term “including” means including but not limited to. The term “based on” means based at least in part on.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2016/042274 | 7/14/2016 | WO | 00 |
