FLUID ANALYSIS WITH CHANNELS FORMED IN LIDS
20220080414 · 2022-03-17
Assignee
Inventors
- Silam J. Choy (Corvallis, OR)
- Alexander GOVYADINOV (Corvallis, OR, US)
- Erik D. Torniainen (Corvallis, OR, US)
- Tod WOODFORD (Corvallis, OR, US)
Cpc classification
B01L2300/041
PERFORMING OPERATIONS; TRANSPORTING
G01N21/6428
PHYSICS
B01L2300/168
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0816
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
In one example in accordance with the present disclosure, a fluid analysis device is described. The device includes a substrate, a die adhered to the substrate, and at least one fluid analysis element disposed on the die. A lid is adhered to the substrate and includes a channel formed thereinto be seated over the die. The device also includes an inlet port to the channel and an outlet from the channel. The inlet port and the outlet port are formed on at least one of the substrate and the lid. A number of electrical traces couple the die to a controller.
Claims
1. A fluid analysis device, comprising: a substrate; a die adhered to the substrate; at least one fluid analysis element disposed on the die; a lid adhered to the substrate, the lid having a channel formed therein to be seated over the die; an inlet port to the channel; an outlet from the channel, wherein the inlet port and the outlet port are formed on at least one of the substrate and the lid; and a number of electrical traces to couple the die to a controller.
2. The fluid analysis device of claim 1, wherein the channel is a serpentine channel which crosses the die to define zones on the die.
3. The fluid analysis device of claim 1, further comprising multiple fluid analysis elements disposed on the die, each fluid analysis element disposed within a zone.
4. The fluid analysis device of claim 1, wherein the die is embedded into the substrate.
5. The fluid analysis device of claim 1, wherein the outlet ports are disposed on the substrate or lid and inlet ports are disposed on the other.
6. The fluid analysis device of claim 1: wherein the lid and substrate form a microfluidic reaction chamber to hold a volume of at least one fluid; and the fluid analysis device comprises multiple dies formed on the substrate in the channel.
7. The fluid analysis device of claim 6, wherein each die is at least one of: an independent physical structure; and comprises a distinct fluid analysis element disposed thereon.
8. The fluid analysis device of claim 6, further comprising a partition disposed between adjacent dies.
9. A fluid analysis system comprising: multiple fluid analysis devices, each fluid analysis device comprising: a substrate; a die adhered to the substrate; at least one fluid analysis element disposed on the die; a lid adhered to the substrate, the lid having a channel formed therein to be seated over the die; at least one inlet port to receive fluid into the channel; at least one outlet port to expel fluid from the channel, wherein the at least one inlet port and the at least one outlet port are formed on at least one of the substrate and the lid; and a number of electrical traces extending outside of the lid to couple the die to a controller, wherein at least one fluid analysis device is coupled to another fluid analysis device.
10. The fluid analysis system of claim 9, wherein the electrical traces are formed in at least one of the lid and the substrate.
11. The fluid analysis system of claim 9, wherein: each fluid analysis device further comprises a second substrate adhered to the substrate; and the electrical traces are formed on the second substrate.
12. The fluid analysis system of claim 9, wherein the lid of at least one fluid analysis device is an optically transparent lid.
13. A method, comprising: receiving a fluid at an inlet of a channel, wherein the inlet is formed in a lid disposed on top of a substrate; passing the fluid through a channel formed in the lid over a die formed on the substrate; performing at least one fluidic operation on the fluid passing through the channel via at least one fluid analysis element disposed on the die; and expelling the fluid through an outlet of the channel, wherein the outlet is formed in the lid.
14. The method of claim 13, further comprising passing the fluid by multiple zones of the die formed on the substrate.
15. The method of claim 13, further comprising performing multiple fluidic operations by performing at least one of: passing the fluid by multiple fluid analysis elements, each disposed on a single die; and passing the fluid by multiple fluid analysis components, each disposed on a different die.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0002] The accompanying drawings illustrate various examples of the principles described herein and are part of the specification. The illustrated examples are given merely for illustration, and do not limit the scope of the claims.
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[0017] Throughout the drawings, identical reference numbers designate similar, but not necessarily identical, elements. The figures are not necessarily to scale, and the size of some parts may be exaggerated to more clearly illustrate the example shown. Moreover, the drawings provide examples and/or implementations consistent with the description; however, the description is not limited to the examples and/or implementations provided in the drawings.
DETAILED DESCRIPTION
[0018] In analytic chemistry, fluid analysis elements are used to analyze fluids or components found within the fluids. For example, the components may be identified, measured, separated, or subject to a variety of fluid operations.
[0019] In some examples, fluid analysis devices such as sensors, actuators, or other components are used to analyze the fluid. According to the present specification, these processes can be performed in situ by a semiconductor die. As a specific example, measurements can be made by sensors disposed on the semiconductor die, chemical reactions can be initiated via a heater disposed on the semiconductor die, and physical manipulation of the fluid can be performed by micro-electro-mechanical systems (MEMS) components fabricated on the die.
[0020] In some examples, multiple fluid operations are carried out on a fluid. Accordingly, the present specification describes how a semiconductor die can be easily and effectively used, and inserted, into a microfluidic chamber as part of a larger fluid network.
[0021] Introducing die analysis functionality in a microfluidic application was performed by creating fluidic ports onto the die or to size the die to accommodate the size of the fluidic part. However, fluidic ports are generally larger (on the scale of greater than 0.5 mm) which constrains how small the die could be. Thus, many fluid analysis systems have a lower limit size based on the ports. In another example, such analysis dies are near, but not in direct contact with, the fluid being transported and manipulated in a fluid network. Accordingly, the results of any fluid analysis may be diminished, the results may include more error, and the overall capability of the die to act upon or measure the fluid is reduced.
[0022] Accordingly, the present specification describes a microfluidic channel with input/output flow ports. The microfluidic channel includes a die, such as a semiconductor die, that is in contact with the fluid passing between the ports. In one specific example, the die may be a complementary metal-oxide-semiconductor (CMOS) die mounted on a substrate. A lid is mounted over the die and onto the substrate with the ends thereof being sealed. Input and output ports may be created through the substrate or the lid and connected to the rest of the fluid network.
[0023] In this example, one end of the die extends out from the microfluidic chamber such that electrical signals and power connections can be provided to the die via electrical routing traces on the substrate.
[0024] In one particular example, the fluid analysis device is included in a microfluidic reaction chamber. A microfluidic reaction chamber refers to a chamber where a chemical reaction, or any other manipulation, processing, or sensing operation occurs. One such example of a reaction is the neutralization of a basic or acidic solution. Specifically, an input sample may have a certain pH and a user may want to change the pH based on downstream analysis. That is, the subsequent analysis operations may be most effective with solutions at a particular pH. Accordingly, a user may titrate various fluids together to change the pH of the solution. In another example, a subsequent operation may include an enzymatic reaction for which a particular pH is desired. Similarly, in this case, the pH of the enzyme may be changed in the sample preparation stage via the addition of another fluid.
[0025] The presence of a die in a microfluidic reaction chamber provides the ability to sense or measure properties of components of the fluid, or the fluid in the chamber. By inserting a semiconductor die into a microfluidic chamber, the semiconductor die is in direct contact with the fluid and can directly measure or act upon the fluid. In some examples, the die may be disposed in a long narrow microfluidic chamber. Accordingly, the die may also be long and narrow. Specifically, the die may be between 5 millimeters (mm) and 50 mm long while being between 50 micrometers (μM) and 1 mm wide.
[0026] As described above in some examples, multiple fluid operations are to be performed on a single fluid sample. These different fluid operations may be carried out by different sensors. In some examples, different sensors may be formed by processes or materials that are incompatible with one another such that it is not possible to place the fluid analysis elements on the same wafer. As a specific example, dichroic filters are placed over photodiodes for sensing components within a fluid. Different filters can be used to detect different components within a fluid. Having different filter properties for distinct photodiodes on the same die implements different thin film layers covering each photodiode. The processes to deposit and pattern these thin film layers at specific thicknesses and sizes over each photodiode on the same die may conflict among photodiodes and inhibit the performance of these thin films. Accordingly, the present specification by separating these photodiodes onto different wafers all while being within a single channel or reaction chamber avoids any associated manufacturing complexities and ensures enhanced performance of the sensors.
[0027] In another example, different types of sensors have different manufacturing processes. For example, an electrochemical sensor that includes electrodes may have different formation processes as compared to a photodiode with a dichroic filter. Similarly, the present specification includes both these components in a single reaction chamber albeit on different wafers.
[0028] In some examples, multiple parallel fluid chambers may be formed, each with a unique die/fluid analysis element. However, doing so splits the analyte which can result in an uneven concentration of analyte in the different chambers and/or a sufficient reduction in concentration and signal thus leading to imprecise analysis results.
[0029] Accordingly, the present specification splits the sensors onto multiple dies, which multiple sensors/dies may have different fabrication properties. In another example, by using a sliver die, such as the high aspect ratio sliver die described above, multiple fluid analysis devices may be placed on a single die due in part to the ability to sufficiently separate the components thereon. In either case, multiple die each with a different fluid analysis element, or a single sliver die with multiple fluid analysis elements disposed thereon, placing these dies themselves in the microfluidic channel or chamber, reduces the added cost of silicon from having multiple dies instead of just one and increases fluid analysis possibilities by allowing fluid analysis of incompatible sensors in a single reaction chamber.
[0030] Specifically, the present specification describes a fluid analysis device. The fluid analysis device includes a substrate, a die adhered to the substrate, and at least one fluid analysis element disposed on the die. The device also includes a lid adhered to the substrate. The lid has a channel formed therein to be seated over the die. The fluid analysis device also includes an inlet port to the channel and an outlet from the channel. The inlet port and the outlet port are formed on at least one of the substrate and the lid. The fluid analysis device also includes a number of electrical traces to couple the die to a controller.
[0031] The present specification also describes a fluid analysis system. The fluid analysis system includes multiple fluid analysis devices. Each fluid analysis device includes a substrate, a die adhered to the substrate, and at least one fluid analysis element disposed on the die. Each device also includes a lid adhered to the substrate, which lid has a channel formed therein to be seated over the die. Each fluid analysis device also includes an inlet port to the channel and an outlet from the channel. The inlet port and the outlet port are formed on at least one of the substrate and the lid. The fluid analysis device also includes a number of electrical traces to couple the die to a controller. In this example, each fluid analysis device is coupled to another fluid analysis device.
[0032] The present specification also describes a method. According to the method, fluid is received at an inlet of a channel, which inlet is formed in a lid disposed on top of a substrate. The fluid is passed through a channel formed in the lid over a die formed on the substrate. At least one fluid operation is performed on the fluid passing through the channel via at least one fluid analysis element disposed on the die. The fluid is then expelled through an outlet of the channel, which outlet is formed in the lid.
[0033] The systems and methods of the present specification 1) place a die/fluid analysis element in direct contact with the fluid to directly measure or act upon the fluid; 2) provide a long narrow die which increases die contact time with the fluid while the fluid flows through the channel, eliminate stagnant volume or air pockets in the channel when the channel is first filled with fluid, and increase surface area of the die in contact with the fluid for a given die footprint; 3) remove the size of the fluid connections as a constraint for fluid analysis systems; 4) place more than one planar surface of the die in contact with the fluid, thus increasing the performance of certain fluid analysis operations; 5) in some cases provide for multiple zones in the channel and on a single die to allow for distinct, and sequential fluid analysis operations; 6) allow sensors and other fluid analysis features that are otherwise incompatible to co-exist in the same microfluidic reaction chamber, by separating fluid analysis elements formed by conflicting fabrication processes onto separate dies; and 7) facilitate fabrication of dies of differing substrate material into a single package.
[0034] Turning now to the figures,
[0035] The fluid analysis device (100) includes a substrate (102) on which other components of the fluid analysis device (100) are formed. The substrate (102) may be formed of a variety of materials including plastic, silicon, glass, metal, or any other rigid material such as a printed circuit board (PCB).
[0036] Disposed on top of the substrate (102) is a die (104), such as a semiconductor die (104). The die (104) provides a mounting surface for the fluid analysis elements (106) that operate on the fluid. The die (104) also provides power and data transmission paths between the fluid analysis elements (106) and the electrical traces (114). The electrical traces (114) couple the die (104) to a controller that provides the signals that control the fluid analysis elements (106). In some examples, the die (104) may be a high aspect ratio die (104). That is, the die (104) may be long and narrow. In some examples, the die (104) may have a length to width ratio of at least 3:1 and potentially greater such as 50:1. For example, the width of the die (104) may be 50 micrometers to 1 millimeter and the length of the die (104) may be from 5 millimeters to 50 millimeters. Using such a high aspect ratio die (104) allows for multiple fluid analysis elements (106) to be placed on the die (104) while allowing sufficient space between them to accommodate different fluidic operations.
[0037] In some examples, the fluid analysis elements (106) may be disposed serially along the die (104) such that sequential operations can be executed. For example, along a flow path a first analysis element (106) may be a heater to initiate a chemical reaction of components of the fluid. A second analysis element (106) along the flow path may be a sensor to analyze the fluid to determine a status, or result, of the chemical reaction. Given the length of the die (104), the fluid may be heated and enough time may pass as the fluid reaches the sensor for the initiated chemical reaction to occur. Moreover, by being narrow, and filling the channel, all of the fluid interacts with both components such that a complete reaction occurs. Thus, a long die (104) as described herein provides for linear fluidic operations to be performed on a single die (104).
[0038] As will be described below, in some examples the fluid analysis device (100) includes multiple die (104). These die (104) may be different types of die (104) that include fluid analysis elements (106) that are manufactured in different, and sometimes incompatible ways, or where the die (104) themselves are manufactured in different and potentially incompatible ways.
[0039] That is, the die (104) may include fluid analysis elements (106) that could not be formed on a traditional single die (104). However, due to the length of the high aspect ratio die (104) which adequately separates the elements, these fluid analysis elements (106) may be formed on a single die (104). That is, in some applications a period of time is desired between performing different operations. A high aspect ratio die (104) with multiple fluid analysis elements (106) disposed in sequential fashion along a flow path of the fluid provides a gap between fluid analysis elements (106), which gap allows for time-dependent sequential operations to be performed. All this may be done on a single die (104) in a single chamber rather than using multiple different fluid analysis devices (100) per operation.
[0040] At least one fluid analysis element (106) is disposed on a die (104) and in some examples multiple fluid analysis elements (106) may be disposed on a die (104). In the case of one fluid analysis element (106) per die (104), the fluid analysis device (100) may include multiple die (104) such that multiple fluid analysis operations can be executed. In the case of multiple fluid analysis elements (106) per die (104), the fluid analysis device (100) may include one or multiple die (104).
[0041] The fluid analysis elements (106) may be of a variety of types and may therefore carry out a variety of operations. Some examples include lysing elements that rupture cell walls, heaters that raise the temperature of fluid, sensing elements that detect the presence of certain fluids, or certain components within a fluid, electrochemical sensors, optical elements, physical manipulators that could mix, cool, separate, filter or interrupt the flow path of the fluid. Another example of a fluid analysis element (106) is a chemical agent applied to the surface of the die (104) or to a pad mounted on the die (104). This chemical agent may react with biochemical reagents in a fluid that capture different proteins. Different kinds of chemical agents may be added to perform any number of chemical analysis/manipulation operations.
[0042] While particular reference is made to a few specific types of fluid analysis elements (106), any type, and any number of fluid analysis elements (106) may be disposed on the die (104), whether the single or multiple fluid analysis elements (106) are disposed on a single or multiple die (104).
[0043] The fluid analysis device (100) also includes a lid (108) that is adhered to the substrate (102). Formed in the lid (108) is a channel. That is, during fabrication a recess is formed in the lid (108). This channel is seated over the die (104). In this way, fluid that passes through the channel is passed over the die (104), thus exposing the fluid to the fluid analysis elements (106) disposed thereon such that the fluid may be acted upon. The lid (108) and the substrate (102) may form a microfluidic reaction chamber to hold a volume of at least one fluid. In such a chamber any number of reactions may be effectuated, such as the aforementioned lysing, physical manipulation, chemical alteration, sensing, etc. The fluid analysis device includes an inlet port (110) to introduce fluid into the channel and an outlet port (112) to expel fluid from the channel. The inlet port (110) and outlet port (112) may be formed on at least one of the substrate (102) and the lid (108).
[0044] Thus, the present fluid analysis device (100) allows for direct contact of a fluid with the fluid analysis elements (106) on a die (104) and does so without being constrained by the size of large fluidic connections.
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[0048] The lid (108) of the fluid analysis device (100) may be formed of a variety of materials. Depending on the application, in some examples the lid (108) may be an optically transparent lid (108). In this example optical signals and/or light may pass through the optically transparent lid (108) to illuminate the fluid passing therethrough, or to aid in any of the fluid analytic/manipulation operations that are executed. Examples of optically transparent materials include glass and polycarbonate.
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[0050] As described above, in some examples, the lid (108) may be formed of an optically transparent material. In other examples, the lid (108) may be formed of another material such as SUB. In this example, the channel (218) may be fabricated during the manufacturing operation for the die (104).
[0051] As described above, the inlet (110) and outlet (112) may be formed in a variety of places. In the example depicted in
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[0054] In some examples, the fluid analysis device (100) also includes an encapsulant (216) disposed over the electrical connection between the die (104) and the electrical traces (114). The connection between the die (104) and the electrical traces (114) may be wire-bonded and in some cases can be fragile. The encapsulant (216) protects the mechanical and electrical robustness of this interface. The encapsulant (216) also serves to seal on end of the channel (218).
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[0056] The channel (
[0057] During use, fluid is introduced into the channel (
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[0060] That is, as described above, the die (
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[0062] In the example depicted in
[0063] Such an offset inlet (110) may also alter the flow dynamics of the fluid. That is, fluid entering the inlet (110) may have a certain velocity that is undesired for the fluid analysis operation of the fluid analysis device (100). Accordingly, the offset inlet (110) may slow the flow into the channel (218) and in some cases may affect its characteristics, i.e., amount of turbulent flow, to a desired state before entering the channel (218) for fluid analysis.
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[0065] During use, fluid is introduced into the channel (218) through the inlet (110). As it travels towards an outlet (
[0066] In some examples, additional adhesive is placed over the die (104) and under the lid (108) in regions that separate the serpentine turns, for example over the dashed regions of the die (104) in
[0067] In some examples, the lid (108) may take a variety of topographical characteristics. For example, the lid (108) may be thinner in the areas not disposed over the die (104). That is, the lid (108) may be thinner in the serpentine bends. In one particular example, this may allow for a more rapid thermal dissipation such that the fluid in the serpentine bends may cool more rapidly.
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[0069] To form embedded die (104), the die (104) may be overmolded during a fabrication of the substrate (102). For example, the substrate (102) may be an epoxy mold compound which is in a liquid form prior to curing. When in a liquid form, the epoxy mold compound may be formed around the die (104) and then cured to enclose the die (104) in the substrate. This operation may also avoid the use of the adhesive to affix the die (104) to the substrate (102).
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[0075] In some examples, different types of these components can detect different color or fluorescent markers. For example, as depicted in
[0076] A specific example of the operation of the fluid analysis device (100) depicted in
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[0078] In some examples, as depicted in
[0079] In some examples, the partitions (1444) may be formed of the same material as the substrate (102) and in other examples may be a different material. In either case, the partition (1444) material may be a low thermally conductive material to prevent the transfer of heat energy to adjacent die (104). Moreover, while
[0080] The systems and methods of the present specification 1) place a die/fluid analysis element in direct contact with the fluid to directly measure or act upon the fluid; 2) provide a long narrow die which increases die contact time with the fluid while the fluid flows through the channel, eliminate stagnant volume or air pockets in the channel when the channel is first filled with fluid, and increase surface area of the die in contact with the fluid for a given die footprint; 3) remove the size of the fluid connections as a constraint for fluid analysis systems; 4) place more than one planar surface of the die in contact with the fluid, thus increasing the performance of certain fluid analysis operations; 5) in some cases provide for multiple zones in the channel and on a single die to allow for distinct, and sequential fluid analysis operations; 6) allow sensors and other fluid analysis features that are otherwise incompatible to co-exist in the same microfluidic reaction chamber, by separating fluid analysis elements formed by conflicting fabrication processes onto separate dies; and 7) facilitate fabrication of dies of differing substrate material into a single package.