The present disclosure is for a device useful for isolating, concentrating, and detecting particles in a fluid utilizing filter panels. More specifically, the device provides a plurality of filter panels aligned in series to isolate a particular sized particle from larger and smaller particles. The arrangement also allows for the concentration of particles within a fluid for ease of detection of the isolated particles.
Various embodiments of the present disclosure teach a filtering device generally constructed from two panels. The device may be used for the isolation, concentration, and detection of particles with particular chosen characteristics. A first panel, an etched or molded filter panel, includes an array of V-shaped channels wherein the walls of the V-shaped channels have spacer pads and offset walls that create filtering pores when the filter panel is mated to a flat surface of a second panel.
The use of semiconductor processing equipment provides incredible accuracy as well as the ability to construct extremely small features.
The accompanying drawings, in which like reference numerals refer to identical or functionally similar elements throughout the separate views, together with the detailed description below, are incorporated in and form part of the specification, and serve to further illustrate embodiments of concepts that include the claimed disclosure, and explain various principles and advantages of those embodiments.
The methods and systems disclosed herein have been represented where appropriate by conventional symbols in the drawings, showing only those specific details that are pertinent to understanding the embodiments of the present disclosure so as not to obscure the disclosure with details that will be readily apparent to those of ordinary skill in the art having the benefit of the description herein.
A fluid, either a liquid or a gas, enters the device from the backside of the filter panel 1, and flows to the frontside of the filter panel 1 through an inlet port 2. The fluid flows from the inlet port 2 and is distributed to a plurality of inlet V-shaped channels 4 via inlet plenum 3.
A large number of the inlet V-shaped channels 4 are arranged next to one another in a parallel flow configuration. The inlet V-shaped channels 4 are in fluid communication with each other so that the fluid is constrained to flow down the inlet V-shaped channels 4. The inlet V-shaped channels are joined at the inlet pad ends 10.
The inlet plenum 3 is constructed to deliver fluid to each of the inlet V-shaped channels 4 at generally the same flow rate. Pore walls 5 extend from the base surface 6 of the filter panel 1 to form the walls of the V-shaped channels 4. Top surfaces of the pore walls 5 contact the cover panel 1′. The end pads 10 also extend from the base surface 6 and extend to and mate with the cover plate 1′.
A border plane 9 also mates with the cover panel 1′. The border plane 9 directs the flow of fluid from the inlet plenum 2 to the inlet V-shaped channels 4. On the opposite side of the pore walls 5, the outlet V-shaped channels 7 are formed and connect to an outlet plenum 8. The fluid flow path continues from the outlet plenum 8 to the outlet port 18.
Either the inlet port 2 or the outlet port 18 or both elements can be configured on the cover panel 1′ for manufacturing convenience. Further, the inlet port 2 and the outlet port 18 can extend to the sides of the filter panels from their respective plenums.
A closeup of the upper section of the outlet area can be seen in
A still further magnified view of the pore walls 5 is shown in
The dimensions of the stepped wall from wide and tall to narrow and short is chosen to be optimal for manufacturing, durability, and flow characteristics of a given application. For durability reasons the stepped wall is preferably a single narrow wall that is relatively tall. For a filter device in which small pores are desired, in the range of tens of nanometers, the dimensions of the walls might be as follows: narrow wall 15 of 20 nm wide by 20 nm tall; medium wall 14 of 200 nm wide by 200 nm tall; and wide pore wall 13 10 um wide by 20 um tall. For a filter device with moderate sized pores, in the range of hundreds of nanometers, the sizes of the walls might be: narrow wall 15 200 nm wide wall by 200 nm tall; medium wall 14 4 um wide by 4 um tall; and wide pore wall 13 20 um wide by 50 um tall.
By utilizing pores constructed with wide, medium, and narrow walls, the flow rate of the filter device is increased as compared to a filter device utilizing only a single wall with the same size pores. The flow rate of a narrow wall 200 nm wide would be 200 times greater than that of a 20 um wide wall. This is based on the equation for flow rate in a channel where the flow rate has an inverse linear relationship to the width of the wall (commonly referred to as channel length in reference to the general equation for flow rate).
As mentioned above, semiconductor processing equipment is one option to manufacture the filter panels. With semiconductor processing equipment the pore size can be controlled within the size of one atom or molecule. Atomic layer deposition (ALD) is a process in which one atomic layer of material is deposited at a time during processing. This enables the construction of filter devices with pores of one atom accuracy. ALD would typically be used to create the spacer pads 12 that define the pore size in the filter panel 1.
Referring to
In many cases it is desirable to know if a particle has been retained in a filter device. A light source and a detector can readily be deployed to detect particles within a filter panel. Detection can be accomplished by directing a light source to the pore 16. The light is either allowed to pass uninterrupted in the absence of a particle, or the path of the light is disrupted by the presence of a particle 25. The degree of the disruption of the light can be equated to the number and/or size of particles collected at the pore 16. One skilled in the art of light sources and detectors could devise many ways to illuminate the pores and detect the disruption of the light by particles. At least one of the filter panels would need to be optically transparent to use light as the detection method.
The pores in the first filter 32 in a multiple filter configuration are slightly larger than the pores in the second filter 34 and successive filters. When a fluid flows through both of these filter panels 32, 34, particles within a given size range are collected at the first filter 32, while particles smaller than the first filter 32 pores but still within the specified particle size range are collected at the pores of the second filter 34.
For example, if the size range of particles to be extracted is 99 nm to 101 nm (the current understanding of the diameter of SARS-CoV-2 virus), the first filter 32 pores would be 101 nm in size, thereby retaining all particles larger than 101 nm. The fluid solution that passed through the first filter 32 would contain particles smaller than 101 nm. The pores in the last filter panel in the sequence, in this example the second filter panel 34, would be fabricated at 99 nm in size. This would result in the collection of particles larger than 99 nm at the second filter 34. Both particles smaller than 99 nm and the carrier fluid in the solution would pass through the second filter panel 34 and exit the outlet port 18. Only particles from 99 nm to 101 nm are collected in the filter panel 34.
Note that with ALD processing, the pores can be manufactured to be almost exactly 101 nm. The pores can be as accurate within the diameter of one atom or molecule. In the case of silicon dioxide, SiO2 the molecular diameter is 0.15 nm. This accuracy and precision combined with the detection methods discussed above forms a powerful tool to isolate the then identify a specific range size of particle.
The backwashed solution exiting the backwash port 46 contains particles with a narrow size range that have been collected in the second filter 34. Because of the compact nature of the V-shaped channels and the plenums, only a small amount of backwash fluid is required. Many liters of fluid can be run through the backwash filter panel 40. The first filter panel 32 would collect a portion of the particles in an initial solution. The size of the first filter 32 may need to be large in overall size if the solution inlet to the device contains a high percentage of relatively large particles. In most typical cases, the second filter 34 does not need to be as large as might be required for the first filter panel 32 because the second filter panel 34 is only collecting a relatively small number of particles. Thus, only a small amount of backwash fluid is needed to clear the particles from the second filter 34 and out the backwash port 46. The backwashed solution can be observed by a light scattering detector or a more complex instrument to further evaluate the sample's contents.
The ratio of the initial sample fluid volume to the backwash fluidic volume can be very large—hundreds or even thousands to one. This is highly desirable when trying to detect a small amount of a pathogen in a large volume of sample fluid. SARS-CoV-2 is one particular particle of interest. Both isolation and concentration of the virus is desired. The invention disclosed herein can accomplish both with a high degree of accuracy and consistency.
It should also be mentioned that inexpensive polymer copies of a semiconductor master of the filter device can be created. This is a common practice in the fabrication of microfluidic devices. Metal copies are also an option.
With extremely small particles the electrical charge on the surface of the particle or the surface of the filter may affect filtration. A charge interaction between the particle and the filter can be overcome by increasing the force on the particle and can be used to filter particles, in part as a function of their charge.
An example of the need to separate particles by both size and elasticity would be the separation of circulating tumor cells (CTC's) from a blood sample. CTC's and white blood cells overlap in size, but they differ greatly in elasticity. By deploying a filter with elasticity discrimination, CTC's can be more effectively separated from a blood sample than simply selecting by size.
Adjustable pore size can be used not only to filter different sized particles within one filter device, but also to flush particles captured by the pores. Captured particles can be released from the pores by reducing the force on the elastic spacer pads 52. The released particles can be collected for further analysis or detection. The particles can also be released so that the filter can expel all particles and be “cleaned” for reuse.
A pressure gage 68 can be deployed to monitor the fluid pressure. The flow rate and pressure would initially be low. As the flow rate is increased, highly elastic particles retained by the adjustable filter 60 would be expelled from the pores of the filter panel 60. The valve 65 directs the output of the adjustable filter 60 to the sample reservoir 69. The contents of the sample reservoir 69 can be evaluated by a local detector, or transferred to another device for analysis.
The adjustable pores of the adjustable filter 60 could be reduced in size to remove smaller particles from the sample remaining in the sample reservoir. And again, pressure from increased flow can be used to further separate the particles by their elasticity.
The fluids processed by the filter panels discussed above are generally liquids. It should be noted that the disclosed filter panels can be used with gases as well as with fluids. Further, a combination of liquids and gases could be processed. A significant combined liquid/gas application of significance would be using air to backwash particles from filters such as those disclosed above relative to
Another significant liquid/gas example would be the isolation of a particle from large quantities of air. By backwashing particles collected from air with water, the isolated particles would be retained within a liquid. Liquid is often the preferred type of fluid for analysis with analytical instruments.
The description of the present disclosure has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the present disclosure in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the present disclosure. Exemplary embodiments were chosen and described in order to best explain the principles of the present disclosure and its practical application, and to enable others of ordinary skill in the art to understand the present disclosure for various embodiments with various modifications as are suited to the particular use contemplated.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the technology. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
It will be understood that like or analogous elements and/or components, referred to herein, may be identified throughout the drawings with like reference characters. It will be further understood that several of the Figures are merely schematic representations of the present disclosure. As such, some of the components may have been distorted from their actual scale for pictorial clarity.
In the following description, for purposes of explanation and not limitation, specific details are set forth, such as particular embodiments, procedures, techniques, etc. in order to provide a thorough understanding of the present invention. However, it will be apparent to one skilled in the art that the present invention may be practiced in other embodiments that depart from these specific details.
Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” or “according to one embodiment” (or other phrases having similar import) at various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Furthermore, depending on the context of discussion herein, a singular term may include its plural forms and a plural term may include its singular form. Similarly, a hyphenated term (e.g., “on-demand”) may be occasionally interchangeably used with its non-hyphenated version (e.g., “on demand”), a capitalized entry (e.g., “Software”) may be interchangeably used with its non-capitalized version (e.g., “software”), a plural term may be indicated with or without an apostrophe (e.g., PE's or PEs), and an italicized term (e.g., “N+1”) may be interchangeably used with its non-italicized version (e.g., “N+1”). Such occasional interchangeable uses shall not be considered inconsistent with each other.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
While specific embodiments of, and examples for, the system are described above for illustrative purposes, various equivalent modifications are possible within the scope of the system, as those skilled in the relevant art will recognize. For example, while processes or steps are presented in a given order, alternative embodiments may perform routines having steps in a different order, and some processes or steps may be deleted, moved, added, subdivided, combined, and/or modified to provide alternative or sub-combinations. Each of these processes or steps may be implemented in a variety of different ways. Also, while processes or steps are at times shown as being performed in series, these processes or steps may instead be performed in parallel, or may be performed at different times.
While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not limitation. The descriptions are not intended to limit the scope of the invention to the particular forms set forth herein. To the contrary, the present descriptions are intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims and otherwise appreciated by one of ordinary skill in the art. Thus, the breadth and scope of a preferred embodiment should not be limited by any of the above-described exemplary embodiments.