Patent Application
20220331799
The present invention is directed to a recirculation system for use in microfluidic centrifugal disc platforms for reusing and mixing an entire sample.
Limit of detection is one of the key restriction factors in point of care diagnostic devices. The target molecules in the patient sample are often too scarce to be detected. Ways to overcome the issue include molecular amplification, increasing sample amount, and using more sensitive instruments, which is not practical in point-of-care scenarios.
One of the current solutions for enhancing the limit of detection was previously reported as a reciprocation system. The reciprocation system of multiplexing immunoassay provides maximum exposure of the antigen array to the serum solution to promote target hybridization without increasing the sample amount [Noroozi, Zahra, et al. “A multiplexed immunoassay system based upon reciprocating centrifugal microfluidics.” Review of Scientific Instruments 82.6 (2011): 064303]. However, the method only partially uses the sample due to the ‘back and forth’ motion that only allows the middle part of the sample to be exposed to the detection array. Meanwhile, the reciprocation system does not mix the sample due to the low Reynolds number, resulting in locally depleting the target molecules and hindering the assay accuracy. Thus, there exists a present need for a centrifugal disc (CD) recirculation system capable of using the entire liquid sample and sufficiently mixing the liquid sample as it passes through the system.
It is an objective of the present invention to provide systems and methods that allow for reusing and mixing an entire sample in a centrifugal disc platform, as specified in the independent claims. Embodiments of the invention are given in the dependent claims. Embodiments of the present invention can be freely combined if they are not mutually exclusive.
The present invention features a system for observing and recirculating liquid in a microfluidic centrifugal disc (CD) platform to recycle a sample contained in the liquid. In some embodiments, the system may comprise a reservoir fluidly connected to the CD platform capable of spinning the liquid at various speeds. The system may further comprise an input channel fluidly connected to the CD platform with asymmetric resistance. The system may further comprise a detection array fluidly connected to the channel for observing the sample contained in the liquid. The system may further comprise a pressure chamber comprising an elastic membrane cover. The liquid directed into the pressure chamber may inflate the elastic membrane cover to store pneumatic energy. The system may further comprise a recirculation channel fluidly connecting the pressure chamber to the reservoir. The recirculation channel may have a resistance lower than the channel upstream resistance. When the CD platform spins at a high RPM, the liquid may be directed from the reservoir downstream through the input channel, over the detection array, and into the pressure chamber such that the elastic membrane inflates and stores pneumatic energy. When the RPM of the CD platform rapidly decreases from the high RPM to a low RPM, the liquid may be directed by a release of the pneumatic energy stored in the pressure chamber from the pressure chamber upstream through the channel and the recirculation channel to the reservoir, such that the liquid travels through the recirculation channel faster than the liquid travels through the channel.
The present invention features a method for observing and recirculating liquid in a microfluidic CD platform to recycle a sample contained in the liquid. In some embodiments, the method may comprise filling a reservoir fluidly connected to the CD platform with the liquid and actuating the CD platform at a high RPM such that the liquid travels from the CD platform to an input channel fluidly connected to the CD platform. The input channel may have asymmetric resistance. The method may further comprise directing the liquid through the input channel to a detection array and observing the sample contained in the liquid. The method may further comprise directing the liquid from the detection array to a pressure chamber, such that the liquid inflates an elastic membrane of the pressure chamber and stores pneumatic energy. The method may further comprise decreasing rapidly the RPM of the CD platform to a low RPM such that the pneumatic energy stored in the pressure chamber is released, and directing, by the release of the pneumatic energy, the liquid from the pressure chamber upstream through the channel and a recirculation channel to the reservoir. The recirculation channel resistance is lower than the channel upstream resistance.
The recirculation mechanism moves the sample on the centrifugal microfluidic CD in a circular fashion, which allows all the liquid to flow through the detection area repeatedly. It maximized the utilization of the sample and promoted mixing compared to reciprocating mechanisms. Besides, this novel mechanism enables other detection methods such as flow injection analysis, which requires a large amount of sample.
One of the unique and inventive technical features of the present invention is the use of an elastic membrane for storing pneumatic energy. Without wishing to limit the invention to any theory or mechanism, it is believed that the technical feature of the present invention advantageously provides for the recirculation of a liquid sample in a CD platform while also mixing the sample, as well as allowing for inward pumping in the present invention. None of the presently known prior references or work has the unique inventive technical feature of the present invention.
Furthermore, the inventive feature of the presently claimed invention is counterintuitive. The reason that it is counterintuitive is because it contributed to a surprising result. One skilled in the art would not even attempt inward pumping in a CD platform as the natural fluidic process of liquid in a CD platform causes the liquid to pump outwards in response to the high rotational energy. Surprisingly, the implementation of the elastic membrane and specific structure of the presently claimed invention allow for both outward AND inward pumping in a CD platform, something that could not be possible in any prior CD platforms. Thus, the inventive feature of the presently claimed invention contributed to a surprising result and is counterintuitive.
Any feature or combination of features described herein are included within the scope of the present invention provided that the features included in any such combination are not mutually inconsistent as will be apparent from the context, this specification, and the knowledge of one of ordinary skill in the art. Additional advantages and aspects of the present invention are apparent in the following detailed description and claims.
The features and advantages of the present invention will become apparent from a consideration of the following detailed description presented in connection with the accompanying drawings in which:
Following is a list of elements corresponding to a particular element referred to herein:
The present invention provides a recirculation mechanism for mixing and reusing the liquid in microfluidic systems on CD platforms. The main advantage of this system is that it provides a circular movement of the sample in a centrifugal microfluidic system to recycle the sample. This enables a variety of detection methods that were not able to perform on CD before due to limited sample volume, such as flow injection analysis. Besides the high binding efficiency of target molecules, it also provides efficient mixing capability compared to the traditional reciprocation mechanism.
Referring now to
When the CD platform (160) spins at a high RPM, the liquid may be directed from the reservoir (110) downstream through the input channel (120), over the detection array (140), and into the pressure chamber (150) such that the elastic membrane (155) inflates and stores pneumatic energy. When the RPM of the CD platform (160) rapidly decreases from the high RPM to a low RPM, the liquid may be directed by a release of the pneumatic energy stored in the pressure chamber (150) from the pressure chamber (150) upstream through the input channel (120) and the recirculation channel (130) to the reservoir (110), such that the liquid travels through the recirculation channel (130) faster than the liquid travels through the input channel (120).
In some embodiments, the high RPM and the low RPM may be dependent on one or more mechanical properties of the elastic membrane (155), such as Young's modulus, membrane size, shape, and durability. The RPM may be additionally dependent on the size of the CD. This may allow for the flexibility of a broader range of RPMs implemented by the presently claimed invention. In some embodiments, the high RPM is 4000 to 6000 RPM, the low RPM is 0 to 10 RPM, and the rapid decrease of RPM is a decrease of about 10000 RPM/s. In some embodiments, the high RPM is greater than 3000 RPM. In some embodiments, the input channel (120) may be capable of mixing the sample into the liquid as the liquid passes downstream through the input channel (120). A shape of the input channel (120) may be selected from a group comprising a tesla valve shape, a serpentine shape, and a combination thereof. The detection array (140) may comprise a plurality of microarrays and implement flow injection analysis to observe the sample contained in the liquid. The CD platform (160) may comprise a top CD and a bottom CD (165) connected by an adhesive (300). The CD platform (160) may further comprise a ring adhesive disposed between the elastic membrane (155) and the bottom CD (165). In some embodiments, the elastic membrane (155) may have a diameter at most equal to the diameter of the CD platform (160). In some embodiments, the elastic membrane (155) may have a diameter at least equal to the diameter of the ring adhesive (157). Changing the diameter of the elastic membrane (155) may result in different inward pumping efficience and may affect the transferred volume of fluid per pumping cycle. In some embodiments, the reservoir (110) is a component of the CD platform (160). In other embodiments, the reservoir (110) is an external component from the CD platform (160).
Referring now to
In some embodiments, the high RPM and the low RPM may be dependent on one or more mechanical properties of the elastic membrane (155), such as Young's modulus, membrane size, shape, and durability. The RPM may be additionally dependent on the size of the CD. This may allow for the flexibility of a broader range of RPMs implemented by the presently claimed invention. In some embodiments, the high RPM is 4000 to 6000 RPM, the low RPM is 0 to 10 RPM, and the rapid decrease of RPM is a decrease of about 10000 RPM/s. In some embodiments, the high RPM is greater than 3000 RPM. In some embodiments, the input channel (120) may be capable of mixing the sample into the liquid as the liquid passes downstream through the input channel (120). A shape of the input channel (120) may be selected from a group comprising a tesla valve shape, a serpentine shape, and a combination thereof. The detection array (140) may comprise a plurality of microarrays and implement flow injection analysis to observe the sample contained in the liquid. The CD platform (160) may comprise a top CD and a bottom CD (165) connected by an adhesive (300). The CD platform (160) may further comprise a ring adhesive disposed between the elastic membrane (155) and the bottom CD (165). In some embodiments, the elastic membrane (155) may have a diameter at most equal to the diameter of the CD platform (160). In some embodiments, the elastic membrane (155) may have a diameter at least equal to the diameter of the ring adhesive (157).
In some embodiments, the present invention features a microfluidic CD system capable of inward pumping. The system may comprise a CD platform having a center of rotation, a loading chamber comprising an inlet hole, a recirculating chamber comprising an elastic membrane cover fluidly connected to the loading chamber by an inlet channel with high fluidic resistance, and a collection chamber fluidly connected to the recirculating chamber by a recirculating channel with low fluidic resistance. The collection chamber may comprise a ventilation hole. A liquid may be introduced to the loading chamber through the inlet hole. The CD may then spin at a high RPM to propel the liquid into the recirculating chamber and inflate the elastic membrane. Upon fast deceleration, the return of the elastic membrane to its initial position may push the liquid from the recirculating chamber towards the center of the CD platform through two channels with distinct resistances. The wider recirculation channel has a lower fluidic resistance than the narrower winding inlet channel. As the volumetric flow rate of liquid is much higher in the channel with a lower resistance recirculating channel, most of the liquid is pumped inwards through the recirculating channel and arrives at the collection chamber. The liquid left in the loading chamber and recirculating chamber can be further pumped inwards by repeating spinning and decelerating the CD platform, denoted as the recirculating cycles. This inward pumping method may allow for the transport of a liquid in a CD platform from an outer position to an inner position, contrary to prior CD platforms that only allow for the transport of fluids from an inner position to an outer position.
In some embodiments, the detection array (140) may be capable of both detecting the presence of the liquid at a point in the CD platform (160) and monitoring the fluidic properties of the liquid within the CD platform (160). The detection array (140) in general may provide for a detection method for biological assays.
Although there has been shown and described the preferred embodiment of the present invention, it will be readily apparent to those skilled in the art that modifications may be made thereto which do not exceed the scope of the appended claims. Therefore, the scope of the invention is only to be limited by the following claims. In some embodiments, the figures presented in this patent application are drawn to scale, including the angles, ratios of dimensions, etc. In some embodiments, the figures are representative only and the claims are not limited by the dimensions of the figures. In some embodiments, descriptions of the inventions described herein using the phrase “comprising” includes embodiments that could be described as “consisting essentially of” or “consisting of”, and as such the written description requirement for claiming one or more embodiments of the present invention using the phrase “consisting essentially of” or “consisting of” is met.
The reference numbers recited in the below claims are solely for ease of examination of this patent application, and are exemplary, and are not intended in any way to limit the scope of the claims to the particular features having the corresponding reference numbers in the drawings.
This application is a non-provisional and claims benefit of U.S. Provisional Application No. 63/175,893 filed Apr. 16, 2021, the specification of which is incorporated herein in its entirety by reference
| Number | Date | Country | |
|---|---|---|---|
| 63175893 | Apr 2021 | US |
