EP1611955A1

EP1611955A1 - Microfluidic chip assembly with filtering channel

Info

Publication number: EP1611955A1
Application number: EP04103111A
Authority: EP
Inventors: Konstantin Choikhet; Stefan Falk-Jordan; Andreas Ruefer
Original assignee: Agilent Technologies Inc
Current assignee: Agilent Technologies Inc
Priority date: 2004-07-01
Filing date: 2004-07-01
Publication date: 2006-01-04

Abstract

A microfluidic chip is provided with one or more wells (1) having one or more orifices (3) being interfaces to at least one channel (4,4') for the reception and transport of fluidic chemical and/or biological materials that may contain or form particles (7). The at least one channel (4,4') has at least two portions having different cross sectional shapes (A,B,B'), a first cross sectional shape (A) of which is being sized in a way that that some of the particles (7) are allowed to pass through and a second cross sectional shape (B,B') of which is being sized in a way that some of the particles (7) are retained, thus permitting filtering of the fluid. A method for filtering fluid chemical and biological substances is provided by the use of this microfluidic chip.

Description

The present invention relates to a microfluidic chip assembly.

BACKGROUND ART

Fluidic microchip technologies are increasingly utilized in order to carry out chemical or biological laboratory functions such as experiments, analyses or preparation. These miniaturized instruments allow the performance of traditional and new developed processes under a perfectly controllable setting of parameters. Furthermore, the development of instruments permitting to conduct experiments with very small volumes of e.g. substances that are hard to prepare or very expensive has enabled scientists to proceed in research remarkably.
According to Broyles et al. (B. Scott Broyles, Stephen C. Jacobson, J. Michael Ramsey, Anal. Chem. 2003, 75,2761-2767), micro-fabricated devices were demonstrated integrating sample filtration. Filtering of the sample was accomplished at the sample inlet with an array of channels.
An invention relating to a microfluidic device providing an optimized transport and guide of fluids is already disclosed in Patent Application US 2003/0000835 A1 to Witt et al. A microchip that is capable of mixing sample material in various portions is described in U.S. Pat. No. 6,062,261 to Jacobson et al. DE 103 09 583 A1 to Schoppe et al. refers to a micro plate with an integrated microfluidic system for parallel processing of small fluid volumes. Microfluidic devices, systems and methods of using the same, incorporating channel profiles aim for an improved fluid transport are disclosed in U.S. Pat. No 5,842,787 to Kopf-Sil et al.

DISCLOSURE OF THE INVENTION

It is an object of the present invention to provide an improved filtering of fluidic chemical and biological materials being processed in microfluidic chip assemblies. This object is solved by the independent claims. Preferred embodiments are shown by the dependent claims.
Embodiments of the present invention address the aforementioned needs in the art and provide a microfluidic chip assembly in which the chan nel or capillary system has a filtering function.
Chemical or biological fluids which are subjected to processes in microfluidic chips and which contain particles from the very beginning when they are introduced into the microfluidic chip system, or which form particles due to chemical, physical or biological reactions during their residence time in the system have to be filtered in order to avoid blockage of the fluid flow and to guarantee the reliability of results obtained by using these chips. Thus it is desirable to retain particles.
The present invention provides a microfluidic chip assembly wherein the channel comprises a kind of filter or frit. The central improvement of the present invention is to use the channel or capillary, which opens into the well, itself as a filtering instrument at the channel/well interface or during the course of the channel(s). This is achieved substantially by deformation of the channel in order to create different cross sectional shapes.
In one embodiment of the invention, only one channel is shown, having substantially two different cross sectional shapes, one of which being sized rather circular or of any other form with an aspect ratio close to 1, thus providing depth being big enough to guarantee the foreseen hydraulic flow of the fluid and allowing particles to pass, the other one being sized so flat and wide, creating a very shallow channel, that particles are retained but the hydraulic flow of the fluid is maintained.
In another embodiment of the present invention one main channel is split into several side channels forming a "river delta", each of which side channels opening into the well by which the fluid is introduced into the channel system. The cross sectional shapes are designed in a way not to allow particles to pass.
In an additional embodiment of the present invention one main channel is split into two side channels shaping a "Y", each of which side channels opening into the well by which the fluid is introduced into the channel system, again realizing the filtering effect by designing shallow channels causing the retaining of particles by maintenance of the desired flow through.
As a further embodiment of the present invention, one "main" channel is shown, being deformed not at the well/channel interface but during its course, in order to retain particles, which have been formed in the channel system during the process.
In a still further embodiment of the invention, a method is shown according to which a chemical or biological fluid is introduced into a well of a microfluidic chip, being filtered at the channel/well interface or in the course of the channel, the filtering effect being achieved by deformation of the channels at the corresponding portions.
By the use of microfluidic chip assemblies with filtering effects according to the present invention the lifetime of the microfluidic chip can be prolonged since particles having been retained within the well can be removed by performing a cleaning step. Furthermore, the reliability of experimental results can be optimized by maintaining the initial setting of the microfluidic chip assembly including the maintenance of a homogeneous fluid flow.

BRIEF DESCRIPTION OF DRAWINGS

Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of preferred embodiments in connection with the accompanied drawings. Features that are substantially or functionally equal or similar will be referred to with the same reference signs. The Figures show:
FIG. 1a a cross sectional side view of a part of a chip composed of two components, comprising one well and a conventional channel,
FIG. 1b a plan view of FIG. 1a,
FIG. 1c a detail of FIG. 1 b: the cross sectional shape of the channel,
FIG. 2a a cross sectional side view of a part of a chip composed of two layers, comprising one well and channel with substantially two differing cross sectional shapes,
FIG. 2b a plan view of FIG. 2a,
FIG. 2c detail of FIG. 2b: the cross sectional shape of the channel at the channel/well interface,
FIG. 2d a detail of FIG. 2b: the cross sectional shape of the channel during its course,
FIG. 3a a plan view of another embodiment of the present invention comprising well and channel as in FIG. 1a, but with another design of the channel and channel/well interface, the "river- delta" design,
FIG. 3b an enlarged detail of FIG. 3a: the cross sectional shape of the channel at the channel/well interface,
FIG. 3c a detail of FIG. 3a: the cross sectional shape of the channel in its course,
FIG. 4a a plan view of another embodiment of the present invention comprising well and channel as in FIG. 1a, but with another design of the channel and channel/well interface, the "Y" design
FIG. 4b an enlarged detail of FIG. 4a: the cross sectional shape of the channel at the channel/well interface,
FIG. 4c a detail of FIG. 4a: the cross sectional shape of the channel along its course,
FIG. 5a a plan view of another embodiment of the present invention comprising well and channel as in FIG. 1a, the channel having different cross sectional shapes in its course,
FIG. 5b a detail of FIG. 5a: the cross sectional shape of the channel in a first portion of the channel,
FIG. 5c a detail of FIG. 5a: the cross sectional shape of the channel in a second portion of the channel,
FIG. 5c a detail of FIG. 5a: the cross sectional shape of the channel in a third portion of the channel.
Before the invention is described in detail, it is to be understood that this invention is not limited to the particular component parts of the chips described or to process steps of the methods described as such chips and methods may vary. It is also to be understood, that the terminology used herein is for purposes describi ng particular embodiments only and it is not intended to be limiting. It must be noted that, as used in the specification and the appended claims, the singular forms of "a", "an", and "the" include plural referents until the context clearly dictates otherwise. Thus, for example, the reference to "an orifice" includes two or more such orifices being comprised in a channel design according to the present invention; "a channel" or "the channel" may as well include two or more channels, where it is reasonably in the sense of the present invention.
In this specification and in the claims which follow, reference will be made to the following terms which shall be defined to have the herewith explained meanings:
"Substantially two different cross sectional shapes" means herein, that the transition portion between two different cross sectional shapes is not considered.
A "channel" comprises as well channels that are micro- or nano sized, thus being capillaries.
A "well" is a cavity in a microfluidic chip serving as reservoir for fluids.
A "caddy" is the cowl being mounted on the cavity in order to help carrying fluids.
The present invention depicts an assembly of a microfluidic chip, which is provided for subjecting chemical or biological fluids to analysis or preparation steps. A plurality of wells is comprised in the chip, serving as reservoir for fluidic chemical and biological substances. In order to transport the fluid from a well across the chip to e.g. an analysis device, channels are generated within the chip. The chip body substantially comprises a system of microfluidic channels in a solid body or housing, which is preferably planar and is made of quartz, glass, polymer material or the like. The channels can be e.g. etched in one of the planar plates, opening into the wells, thus linking the wells with the corresponding device. The etched structures are usually closed to form channels by bonding another planar plate on the etched side of the first plate. The chips can also be of multilayer structure, non-planar and so on. As it is known from the art, the channel interfaces to the wells are of the same width and depth as the further course of the channel, furthermore it is possible that the channel narrows in its downstream sections.
The fluid which is processed in those microfluidic chips may occasionally contain particles such as dust particles from the very beginning when it is introduced into the well or particles may be formed due to chemical, physical or biological processes during the residence time of the fluid in the channel system.
The fluid is moved through the channel by means of moving forces, providing a desired and preset flow through. Since the fluid moves, defined hydrodynamic and electrical conditions exist within the channel. According to the present invention, blocking or partial obstruction of the channel, or the channel cross section, respectively, is avoided. Thus a significant change of hydrodynamic and electrical conditions within the channel, which would otherwise lead to unreliable results, is prevented.
Referring now to FIG. 1, a microfluidic chip, which is an assembly composed of two parts, one of which being a caddy 10 with well walls and the other one being a chip plate 17 with one well 1 is shown. The caddy 10 has a drilling hole 14 that forms the sidewalls of the well 1, the bottom of which is formed by the chip plate 17. The well serves as reservoir for fluidic chemical and/or biological materials, which may contain particles 7 from the very moment when the fluid is filled into the well or which can form particles 7 during the subsequent process. Each well 1 has an outlet being an orifice 3 which permits that the fluid flows from the well into a channel 4.
FIGS 1b and 1c point out that the channel 4, which opens into the well 1 has a homogeneous cross sectional shape A, which is designed to permit the fluid to pass the channel with a desired flow through rate. In case of the presence of particles having a size that prevents the particles to pass, blockage occurs partially or completely.
Thus, filtering of the fluid must take place within the device. FIG. 2a shows a first embodiment of the present invention wherein the microfluidic chip is substantially built like the conventional microfluidic chip a section of which is shown in FIGS. 1a, 1b, 1c, but instead of the channel 4, a channel 4', 4 with substantially two different cross sectional shapes A and B is comprised. The orifice 3 is the entry into a channel 4', having a cross sectional shape B which is being sized and wide, providing a shallow channel entry in order to retain particles 7 in the well; the width being that large that despite of the filtering function, which is subsequently followed by partial obstruction of this first portion 9 of the channel, the flow cross section is large enough to remain partially open, thus maintaining a desired flow through rate of the fluid from the well through the entire channel. The first portion 9 of the channel 4 transits at the transition portion 15 into a second portion of the channel 4, having cross sectional shape A which is shaped rather circular or semi-circular providing depth in order to lead to optimal flow properties.
FIG. 2b shows a plan view of the device depicted in FIG 2a, in connection with FIGS. 2c and 2d it is pointed out how the cross sectional shape B of the first portion 9 of the channel 4 at the orifice 3 differs from the cross sectional shape A which is provided during the course of the channel 4.
Referring now to FIG. 3a, it is shown a plan view of another embodiment of the present invention depicting a "main" channel 4, which splits at the junctions 12 into "side" channels 4', thus forming a "river delta" design. In FIG: 3a, five orifices 3 can be counted, each having a smaller cross sectional shape A than that of the "main" channel 4, but having in total a larger cross sectional shape than the main channel has.
FIGS. 3b and 3c show the shapes of the cross sections at the orifices 3, channel 4' respectively, and during the course of the channel 4.
It has to be understood that the above embodiments give only examples for the cross sectional shapes or for the design of the transition portion 15 or the junctions 12. Any appropriate design to reach the aims of the present invention can be used.
FIG. 4a shows again a plan view of an additional embodiment of the device of the present invention. Herein, the "main" channel 4, which splits only into two "side" channels 4', forms a "Y". As can be seen in FIG.4b, which gives a detail of FIG 4a, the "side" channel 4 widens and flattens where the channel 4' opens into the well 1. FIG. 4c indicates the cross sectional shape A of the "main" channel 4 during its course. Again, the total of the two cross sectional shapes B is larger than that of the "main" channel 4.
As has been shown in the above FIGS. 3 and 4, a junction 12 within a channel 4 links two channels 4' with the channel 4, thus forming a "Y", or it links more than two channels 4' at once, which is not shown in a Figure, resulting in a "river delta" design. That means in reverse, the "main" channel 4 can split into two or more channels at once. Another possibility is, that one junction 12 links only two channels 4' at once, but two - or more - junctions 12 are located one after the other, leading to five (FIG.3) or more "side" channels 4', interfacing the well in parallel.
Of course, other designs are possible. If a plurality of orifices is arranged very close one next to the other, a design originates that is similar to a lattice.
Referring to FIG. 5a, a further embodiment is pointed out, showing the microfluidic device of the present invention with a design, which is preferably used when the particles 7 form due to chemical, physical or biological processes during the passage of the device. The plan view depicts an embodiment comparable to that one of FIG. 1, but with the decisive difference, that the channel 4 has three different cross sectional shapes A, B, B' in its course, what can be seen clearly in the details shown in FIG. 5b, 5c and 5d. Only one channel 4 opens into the well 1, being subdivided into three portions. Each of which portions has a different cross sectional shape. The first portion begins at the orifice 3, the cross section has a flattened shape. The second portion is wider and more flat than the forgoing first portion, its cross sectional shape B doesn't permit particles to pass and, thus, bears the filter-function. The third and last portion has a rather circular cross sectional shape, thus providing a deep channel, and permits the filtered fluid to flow with an optimal flow velocity. The circumferences of the cross sections are nearly equal in this Figure, but it can be preferable to choose larger circumferences for the cross sectional shapes B or B' in order.
In any of the embodiments, the circumferences of a cross sectional shape A and a cross sectional shape B, B' can be unequal but at least two different cross sectional shapes must be comprised.
Another possibility to obtain the filter effect as pointed out in FIG.5 is to choose identical cross sectional shapes, except of circular or nearly circular shapes, and to arrange two or more adjacent portions 9,9',9" in a way that an appropriate displacement is created, resulting in a filtering effect.
Of course, this channel design can be used for "main" channel 4 as well as for "side" channels 4'. Furthermore it may be reasonable to locate a first portion of a channel 4,4' having a cross sectional shape A downstream to a first portion 9,9' having a cross sectional shape B, B', but when the filtering effect is desired during the course of the channel system since, for example, the formation of particles takes place at a definite portion of the channel due to environmental circumstances, it can be reasonable to locate a portion of a channel 4,4' having a cross sectional shape B, B' downstream to a portion having a cross sectional shape A.
It has to be understood, that the composition of the microfluidic chip as described above, bonding an upper and a bottom layer together, could also be a chip composed of more than two layers or plates. The channel discussed in the above embodiments is etched in the bottom plate, but it can also be etched in the upper plate, as far as the fluid can be moved from the well into the channel. Other methods than etching are also possible in order to create the channels.
The method for retaining particles 7 from fluidic chemical and biological materials, which undergo processing in a microfluidic chip, can be performed by means of a microfluidic device according to the present invention. It comprises introducing the fluidic chemical and biological materials into a well 1 and moving it then via an orifice 3 through a channel 4, 4'. The fluidic chemical and biological substance flows through two or more portions of the channel 4,4', at least two of which having different cross sectional shapes A, B, B'. Particles 7 carried by the fluid are retained when the flow cross-section, which has to be passed, is smaller than the size of the particle 7, thus filtering is performed and the fluid maintains the flow velocity that is desired. It is substantial that the cross-section area of the junction bearing the filtering function or the total cross-section area of the orifices within one such junction is larger than the cross-section of the subsequent channel which is to be protected from entering particles, so that the amount of particles, which otherwise would significantly block the channel can only block an insignificant part of the cross-section of the filtering orifice, thus the behavior in the channel is not disturbed.
The above method, which is performed by a microfluidic device according to the present invention prevents changes of the fluid flow due to blockage or partial obstruction of the channels, thus hydrodynamic and electrical conditions within the channel are maintained, and the reliability of the results is optimized.

Claims

Microfluidic chip assembly with one or more wells (1) for the reception of fluidic materials which contain particles (7) or form particles (7), each of which wells (1) having at least one outlet permitting the fluidic to move into at least one channel (4,4'),
wherein each of the at least one channel (4,4') has at least two portions having different cross sectional shapes (A,B,B'), a first cross sectional shape (A) of which is being sized in a way that some of the particles (7) are allowed to pass through and a second cross sectional shape (B,B') of which is being sized in a way that some of the particles (7) are retained.
The chip of claim 1, wherein the at least one outlet is at least one of an orifice (3) and the entry of a first portion (9).
The chip of claim 1 or any of the above claims, wherein the at least one channel comprises a first channel (4) and a second channel (4') and wherein each of two or more orifices (3) is the entry of a portion (11) of the first channel (4') having a cross sectional shape (B), which transits into the second channel (4).
The chip of claim 1 or any one of the above claims, comprising at least one of the following features:
a. one junction (12) links at least two second channels (4') with the first channel (4), being shaped as a "Y" or a "river-delta", the at least two second channels (4') opening into the well (1);

b. one junction (12) links one second channel (4') with the first channel (4), at least two junctions (12) being located one after the other;

c. one junction (12) links two second channels (4') with the first channel (4), at least two junctions (12) being located one after the other.
The chip of claim 1 or any one of the above claims, comprising at least one of the features:
a. the cross-section areas of the first cross sectional shape (A) and the at least one second cross sectional shape (B, B') are unequal;

b. the cross-section areas of the at least one second cross sectional shape (B,B') is larger than the circumference of the first cross sectional shape (A).
The chip of claim 1 or any one of the above claims, wherein the second cross sectional shapes (B,B') of two adjacent portions (9,9') of the channel (4) are identically and are arranged in a way to provide a displacement of the portions (9,9') of the channel (4,4').
The chip of claim 1 or any one of the above claims, wherein at least one first portion (8) of the channel (4,4') having a first cross sectional shape (A) is located downstream to a first portion (9,9') having a second cross sectional shape (B,B').
The chip of claim 1 or any one of the above claims, comprising at least one of the features:
a. the at least one channel (4,4') comprises three or more portions (8,9,9',11), at least two of which having different cross sectional sizes (A,B,B');

b. the at least one channel (4,4') is a capillary;

c. the fluidic material is chemical and/or biological material;

d. the total cross sectional shape of the second cross sectional shapes (B,B') is at least the same size or greater than the first cross sectional shape (A) or the total of the first cross sectional shapes (A).
A method for retaining particles (7) from fluidic materials which are subjected to processes in a microfluidic chip, in particular in a microfluidic chip of claim 1 or any one of the above claims, comprising:
introducing the fluidic chemical and biological materials into at least one well (1) and moving the fluidic materials via an orifice (3) through at least one channel (4,4'),

wherein the fluidic materials flow through at least two portions (8,9,9',11) of the channel (4,4') having at least two different cross sectional shapes (A,B,B'), a first cross sectional shape (A) of which is being sized in a way that some of the particles (7) are passing through and a second cross sectional shape (B,B') of which is being sized in a way that some of the particles (7) are being retained, the fluidic chemical and biological materials therefore being filtered.
The method of claim 9, wherein the fluidic materials are moved due to moving forces in order to achieve predetermined flow velocity.