Micro-dispensing technologies produce liquid media dosages in volumes of less than one micro-liter. The continuing miniaturization of such technologies in almost all technical areas creates change and opportunity for industry, medical fields, development, and research facilities. Thus, ever-smaller amounts of adhesive, liquid, oil, and/or other fluid media has to be dispensed reliably and accurately with respect to dosage and placement of the media for subsequent dispensing. The precise positioning and quantity of fluids such as reagents or other substances dispensed influence the overall quality of a given micro-dispensing technology.
An apparatus enables precise dispensing of fluids while mitigating manual fluid-filling procedures to load the apparatus before dispensing. The apparatus includes a print head that can be coupled to a substrate to dispense fluid from the substrate in response to a command (e.g., dispense command issued to print head from a processor or controller). A reservoir (or reservoirs) can be mounted (or formed) on the substrate to transport the fluid to the print head. A preloaded storage container, mounted on the reservoir, stores the fluid and provides the fluid to the reservoir in response to pressure applied to the container. The apparatus including the print head can be discarded after dispensing of the fluid. By utilizing the preloaded storage container to load the print head via the reservoir(s), manual fluid-filling procedures can be avoided (e.g., manually filling reservoir via pipette dispenser). Moreover, the preloaded storage container separates the fluid from the print head until after pressure is applied to the container. In this manner, contamination and/or drying of the fluid at the print head can be mitigated until dispensing of the fluid is to commence.
The substrate can be a silicon substrate and the reservoir can be a polymer-based material such as an epoxy molding compound or an injection molding material for example. In some examples, the print head can be a thermal ink jet print head or a piezoelectric print head. The substrate can include a set of electrodes that controls the dispensing of the fluid from the substrate in response to the command, where the command can be issued from a processor or controller to cause the fluid to be dispensed from the print head. The set of electrodes can be connected to a detection circuit on the substrate or print head to detect that the reservoir has been filled with the fluid to facilitate that proper dispensing occurs. For instance, the detection circuit can include an impedance circuit to measure a change of impedance in the substrate or print head as the fluid reaches the substrate. A memory can be provided that is accessible via the set of electrodes, where the memory records a fluid type for the fluid that is stored in the preloaded storage container to verify that the desired fluid will be dispensed before the command is issued. The preloaded storage container can be a blister pack having a flexible membrane to store the fluid. The blister pack includes a cover to hold the fluid in the flexible membrane until pressure is applied to the pack to cause release of the stored fluid.
The substrate 120 can include a set of electrodes (see e.g.,
The fluids described herein can be of various solutions such as based on dispensing solvent-based pharmaceutical compounds and aqueous-based biomolecules including proteins, enzymes, lipids, antibiotics, mastermix, and DNA samples, for example. The apparatus 100 can support various applications that include antimicrobial susceptibility testing, compound secondary screening, enzyme profiling, and polymerase chain reaction (PCR) dispensing, for example. The apparatus 100 can repeatability dispense small (e.g., picoliter) volumes of fluid in a rapid manner to perform many categories of dispensing such as direct dilution, for example. Direct dilution enables low dispense volumes from the print head 110 and provides the ability to titrate solutions across many orders of magnitude of concentration without serial dilution. Thus, the print head 110 can directly titrate by dispensing single drops to achieve low concentrations along with dispensing many fluid drops to achieve higher concentrations.
Other dispensing applications can include drug interaction, where the non-contact nature of print head 110 enables two or more fluids to be precisely jetted into a single well or target location. This enables multi-level synergy experiments for multiple dimethyl sulfoxide (DMSO)-based compounds, and/or enzyme profiling experiments of DMSO-based inhibitors and aqueous-based enzymes, antibiotics, or substrates, for example. Other dispensing applications include assay miniaturization, where the low dispense volume of the print head 110 enables the miniaturization of many different assays, including the dispensing of PCR-assay components, including master mix, and primer, for example. While previous dispensing systems utilize dry reservoirs that the end-user was expected to fill via pipette or other manual filling procedure, the apparatus 100 can preload fluids via integrated blister packs as the preloaded storage container 140 in one example. The container 140 can then be burst before use (e.g., based on applied pressure), thus, removing a high-skill step (pipetting) from the workflow and thus, reducing potential errors and waste associated with manual pipetting.
The substrate 620 can include a set of electrodes that controls the dispensing of fluid from the print head 610 in response to the command issued at 660 by the processor 670. The set of electrodes can be connected to a detection circuit on the substrate 620 or print head 610 to detect that the substrate and/or print head has received the fluid from the reservoir 630. The detection circuit can include an impedance circuit to measure a change of impedance in the substrate 620 or print head 610 as the fluid reaches the substrate. The detection circuit can provide feedback to the processor 670 via connection 660 to indicate that the fluid has reached the substrate 620 or print head 610 before fluid dispensing begins. A memory (not shown) can be provided (e.g., formed in the substrate) that is accessible via the set of electrodes that records a fluid type for the fluid that is stored in the preloaded storage container 640. The memory can also serve as feedback to the processor 670 via the set of electrodes to facilitate that the desired fluid type will be dispensed.
The system 600 can include one or more blister-pack reservoirs integrated into a fluidic molded interconnect apparatus. Preloaded reagent reservoirs 630 can be provided in several example configurations. In one example, blister film layers can be integrated into a molded reservoir (e.g., epoxy molding compound (EMC) or injection molded plastic). In one example configuration, a single blister reservoir 630 can feed multiple print/dispense heads 610 via routing through an EMC layer or other type material layer. The print head 610 and/or substrate 620 can include an integrated prime detection circuit (e.g., impedance circuit) to provide closed-look feedback that the fluid reservoir 630 has been filled.
In view of the foregoing structural and functional features described above, an example method will be better appreciated with reference to
Although not shown, the method 700 can also include forming a set of electrodes on the substrate to detect that the fluid has been transported to the substrate or the print head. This can include providing a circuit on the substrate or the print head to measure a change of impedance in the substrate as the fluid reaches the substrate or the print head. The method can also include forming a memory on the substrate that records a fluid type for the fluid that is stored in the preloaded storage container.
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 |
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PCT/US2017/048856 | 8/28/2017 | WO | 00 |