BACKGROUND

[0001] Analytic chemistry is a field of chemistry that uses instruments to separate, identify, quantify, and study matter. Biochemistry is a field of chemistry that includes the study and analysis of the chemistry of living organisms such as cells. Cell lysis is a process of rupturing the cell membrane to extract intracellular components for purposes such as purifying the components, retrieving deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins, polypeptides, metabolites, or other small molecules contained therein, and analyzing the components for genetic and/or disease characteristics. Cell lysis bursts a cell membrane and frees the inner components. The fluid resulting from the bursting of the cell is referred to as lysate.

BRIEF DESCRIPTION OF THE DRAWINGS

[0002] The accompanying drawings illustrate various implementations of the principles described herein and are a part of the specification. The illustrated implementations are merely examples and do not limit the scope of the claims.

[0003] Fig. 1a is an illustration of an input port seal according to an example of principles described herein.

[0004] Fig. 1 b is an illustration of an input port seal according to an example of principles described herein. [0005] Fig. 2 is an illustration of an input port seal according to an example of principles described herein.

[0006] Fig. 3 is a block diagram of a sample preparation device, according to an example of principles described herein.

[0007] Fig. 4 is an illustration of a cartridge with multiple sample preparation devices, according to an example of principles described herein.

[0008] Fig. 5 is a flowchart illustrating a method for preparing a sample, according to an example of principles described herein.

[0009] Fig. 6a is an illustration of a sample preparation device, according to an example of principles described herein.

[0010] Fig. 6b is an illustration of a sample preparation device, according to an example of principles described herein.

[0011] Fig. 6c is an illustration of a sample preparation device, according to an example of principles described herein.

[0012] Fig. 6d is an illustration of a sample preparation device, according to an example of principles described herein.

[0013] Fig. 7 is an illustration of a sample preparation device, according to an example of principles described herein.

[0014] Throughout the drawings, identical reference numbers designate similar, but not necessarily identical, elements.

DETAILED DESCRIPTION

[0015] Cellular analytics is a field of chemistry that uses instruments to separate, identify, quantify, and study cells and their internal components. A wealth of information can be collected from a cellular sample. For example, a study of a patient’s cells may lead to a diagnosis of a disease of a patient. As a particular example, cellular analysis may be used to detect viral nucleic acid such as those that cause the flu. Moreover, a study of cells may lead to the development of medications to treat certain diseases and disorders.

[0016] The intracellular components of the cell also provide valuable information about a cell. Cell lysis is a process of extracting intracellular components from a cell that can also provide valuable information about a cell. During lysis, the intracellular components are extracted for purposes such as purifying the components, retrieving DNA and RNA proteins, polypeptides, metabolites, and small molecules or other components therein, and analyzing the components for genetic and/or disease characteristics. Cell lysis ruptures a cell membrane and frees the inner components. The fluid containing the inner components is referred to as lysate. The contents of the cell can then be analyzed by a downstream system.

[0017] Prior to analysis, the sample to be analyzed is prepared. During preparation, the sample may be lysed and components of the lysate may be bound to magnetic microparticles. Lysing of the sample involves heating and/or chemical exposure and binding which brings the magnetic microparticles into proximity with the components within the lysate. In some examples, the magnetic microparticles are paramagnetic microparticles; in some other examples, the magnetic microparticles are paramagnetic beads.

[0018] That is, in biological assays, a biological component can be intermixed with other components in a biological sample that can interfere with subsequent analysis. As used herein, the term “biological component” may refer to materials of various types, including proteins, cells, cell nuclei, nucleic acids, bacteria, viruses, or the like, that can be present in a biological sample. A “biological sample” may refer to a fluid or a dried or lyophilized material obtained for analysis from a living or deceased organism. Isolating the biological component from other components of the biological sample may permit subsequent analysis without interference and may increase an accuracy of the subsequent analysis. In addition, isolating a biological component from other components in a biological sample may permit analysis of the biological component that would not be possible if the biological component remained in the biological sample. In some examples, the biological component of interest that will be bounded to the magnetic microparticles are nucleic acids (such as DNA and RNA).

[0019] In particular, the present specification describes an input port seal. Directly pipetting into an open port with no input port seal may strand or otherwise trap fluid. The input port seal described herein allows a sample to be precisely directed into the mixing chamber without stranding fluid in the dispenser or in the input port. A user may thus dispense a sample input fluid into the sample preparation device accurately without losing or stranding sample fluid from being processed.

[0020] The input port seal may control the position of the pipette and prevent the pipette from damaging the interior of the input port, mixing chamber, and fluid isolation chamber. The input port seal may further allow otherwise trapped air to vent out so that the mixing chamber does not pressurize and cause leakage of the sample. The input port seal also reduces the potential for fluid to return and become trapped in the sample input port. The input port seal reduces friction with the pipette to allow it to be easily inserted and removed within the input port by the user. The input port seal may also reduce friction between the sample input port and a plunger within the mixing chamber. The input port seal may also capture and control the position of a lyophilized pellet. The input port seal may protect the lyophilized pellet from shipping and handling damage while ensuring that fluid saturates the pellet.

[0021] An example of an input port seal includes a sleeve and an annular flange extending radially outward from an outer wall of the sleeve. The annular flange is to stop the sleeve when the sleeve is disposed within an input port. The outer wall is to seal against walls of the input port. An inner surface of the sleeve is tapered so as to guide movement and positioning of a pipette within the input port. A top opening of the sleeve is to have a larger diameter than a bottom opening. A vent formed through the sleeve is to be communicably attached to a mixing chamber.

[0022] The input port seal may further include that the tapered inner surface be conical shaped. The input port seal may further include that the vent has an opening that extends from a bottom surface of the sleeve to a top surface of the sleeve. The input port seal may further include that the sleeve is friction fit within the input port of the mixing chamber. The input port seal may further include that the sleeve has an elongate channel that extends downward from the bottom opening. The input port seal may further include that the sleeve extends above the input port of the mixing chamber and that a top surface of the sleeve lays flush and seals against a removable cap that is to secure the input port seal to the mixing chamber.

[0023] An example sample preparation device may include a mixing chamber to receive a sample and an input port to introduce the sample into the mixing chamber. A sleeve is insertable into the input port, the sleeve including an annular flange extending radially outward from an outer wall of the sleeve. In an example, the annular flange may stop the sleeve when the sleeve is disposed within the input port. Particularly, the outer wall of the sleeve is to seal against walls of the input port. An inner surface of the sleeve is tapered. In an example, a top opening of the sleeve may include a larger diameter than the bottom opening. A vent formed through the sleeve is to be communicably attached to a chamber. A fluid isolation chamber in fluid communication with the mixing chamber is to receive contents of the mixing chamber. An output is to dispense contents of the fluid isolation chamber to an external environment.

[0024] The sample preparation device may further include an opening in the input port that is to align with a bottom opening of the sleeve when the sleeve is inserted into the input port to allow a sample to be introduced into the mixing chamber. The opening of the input port may be larger in diameter than the bottom opening of the sleeve.

[0025] The sample preparation device may further include that a bottom surface of the sleeve is rounded to conform to a geometry of a lyophilized pellet. The sample preparation device may further include that the interior surface walls of the input port are rounded to conform to a geometry of a lyophilized pellet. The sample preparation device may further include an input vent at a top surface of the mixing chamber adjacent to the input port. The input vent includes an opening that is to align with an opening of the vent to provide fluid communication from the channel to an external environment. The sample preparation device may further include a cap to surround a top portion of the sleeve and the input port to seal the input port and input port seal when not in use. [0026] The present specification also describes a method. An example of a method includes preventing, via tapered walls of an input port seal, a pipette from being improperly positioned and from entering a volume of a mixing chamber. The method further includes sealing, via the tapered walls, the pipette tip to prevent leakage during sample input. The method further includes venting a gas as contents of the pipette are injected into the mixing chamber and are mixed within the mixing chamber. The method further includes covering the input port seal and the input port of the mixing chamber when the pipette is not present.

[0027] The method may further include retaining, via the input port seal, a lyophilized pellet in the input port of the mixing chamber. The method may further include venting a gas from the mixing chamber to an external environment through an input vent in the input port and a vent in the input port seal.

[0028] Figs. 1 a and 1 b are illustrations of an example input port seal 102. The input port seal 102 is used to provide contents to a mixing chamber 112 in conjunction with a sample preparation device 100 as shown in Fig. 3. In addition to an input port seal 102, the sample preparation device 100 shown in Fig. 3 further includes an input port 110, mixing chamber 112, fluid isolation chamber 314, and output 316. Fig. 2 depicts a pipette 120 that is insertable into the input port 110.

[0029] The input port seal 102 includes a sleeve 105 with an inner tapered surface. The inner tapered surface may be conical shaped, or in other words, be an inner tapered cone 104 as shown, that constrains the position of the pipette 120. The inner tapered cone 104 includes a top opening having a larger diameter than a bottom opening. The tapered inner surface of the inner tapered cone 104 prevents a pipette 120 that is inserted within the input port 110 from being improperly positioned and from entering a volume of the mixing chamber 112. The input port 110 includes an opening that is to be co-axially aligned to a bottom opening of the inner tapered cone 104 of the input port seal 102. The alignment allows communication of contents from the pipette 120 to be injected within a volume of the mixing chamber 112 through the opening of the input port 110. The contents are received within the mixing chamber 112 where they are mixed.

[0030] The input port seal 102 may further include a pipette stop 122 that stops insertion of the pipette 120 into the mixing chamber 112. The pipette stop 122 may be an inner shoulder or an annular ridge that extends radially inward from the bottom opening or adjacent to the bottom opening of the sleeve. The pipette stop 122 may have a diameter that is less than the diameter of a tip of the pipette 120 which prevents the pipette 120 from being inserted past the pipette stop 122 and entering the mixing chamber 112. This may prevent contamination of the surface of the pipette 120 with contents already within the mixing chamber 112. Also, the volume within the mixing chamber 112 contains a mixer 148 and a plunger 150. The input port seal 102 stops the pipette 120 from damaging the mixer 148, the plunger 150, a lyophilized pellet 144 (Fig. 7), and minimizes friction upon the plunger 150.

[0031] The input port seal 102 provides a sealing fit and is held in position by features within the input port 110. The sleeve of the input port seal 102 may have a friction fit within the input port 110. The inner walls of the input port 110 and the outer walls of the input port seal 102 may be relatively straight and parallel with a central axis of the input port seal 102. The sealing fit is supported by the annular flange 106 of the input port seal 102. The annular flange 106 may be located at or adjacent to the top of the input port seal 102 and includes an outer facing annular ridge or shoulder that extends radially outward from an outer wall of the sleeve. In this example, the annular flange 106 rests against top edges of the input port 110 and is to stop the input port seal 102 at a fixed distance when the input port seal 102 is being inserted within the input port 110.

[0032] A vent 108 may be formed through the sleeve of the input port seal 102. As shown, the vent 108 is an elongate channel that extends from a bottom surface of the sleeve to a top surface of the sleeve. The vent 108 is to be in fluidic communication with the mixing chamber 112. The input port 110 includes a vent opening 142 that connects to the bottom opening of the vent 108 to complete the access and communication with the mixing chamber 112. The vent 108 may be co-axially aligned with a central axis of the input port 110. The vent 108 may be located elsewhere in the sample preparation device 100.

[0033] Furthermore, multiple vents may be present throughout the sleeve of the input port seal 102 or throughout the sample preparation device 100. In other examples, the mixing chamber 112 has at least one vent or other structure that directly communicates gas, such as air, to an external environment.

[0034] The sleeve of the input port seal 102 may extend above the top of the input port 110 of the mixing chamber 112 when the input port seal 102 is inserted within the input port 110. A top surface of the sleeve is to lay flush and seal against a removable cap 130 that is to secure the input port seal 102 to the input port 110. In another example, the sleeve is at the same height or below the top of the input port 110.

[0035] Note that the opening of the input port 110 is larger in diameter than the bottom opening of the sleeve of the input port seal 102. In this manner, the input port 110 does not occlude the bottom opening of the sleeve of the input port seal 102, which may limit flow and prevent full ejection of the liquid in the pipette. The increase in diameter may also direct flow away from the pipette 120 and into the mixing chamber 112.

[0036] In Fig. 2, an illustration of an example input port seal 102 that is used in conjunction with a sample preparation device 100 is shown. This illustration expands upon Figs. 1a and 1 b to include a full view of the pipette 120, cap 130, and mixing chamber 112. The cap 130 includes a covering that is hinged such that it pivots from an open position to a closed position. In the open position, the cap 130 is removed from the opening of the input port 110. In the closed position, the cap 130 covers the opening of the input port 110. The cap 130 is dimensioned to surround a top portion of the input port seal 102 and input port 110 and thereby seal the input port 110 when not in use.

[0037] The pipette 120 may include an elongate straw-like member that has a length that surpasses the length of the input port 110. The pipette stop 122 (Fig. 1 b) of the input port seal 102 prevents the pipette 120 from being inserted past the bottom opening of the input port 102. [0038] Fig. 3 is a block diagram of a sample preparation device 100, according to an example of the principles described herein. As described above, before a sample is analyzed or processed, the sample may be prepared. Such preparation may include lysing a sample and binding the lysate to magnetic microparticles. The sample preparation device 100 of the present specification carries out at least a portion of the sample preparation.

[0039] The sample preparation device 100 may include a mixing chamber 112 and an input port 110 to receive the sample within the mixing chamber 112. That is, the input port 110 may be in fluid communication with the mixing chamber 112 such that a user may introduce the sample into the mixing chamber 112. For example, a user may insert a pipette 120 into the input port 110 and expel the contents therein into the mixing chamber 112 to begin the sample preparation operation.

[0040] Within the input port 110 is an input port seal 102, which as described above, creates a seal within the input port 110 and has an inner tapered cone 104 to receive and position a pipette 120 for injecting contents within the mixing chamber 112. An annular flange provides a stop for positioning the input port seal 102 within the input port 110. A vent 108 within the input port seal 102 allows fluid and gas to be expelled from within the mixing chamber 112 during the chemical reactions described herein, such as lysing and binding the sample cells to magnetic microparticles are performed.

[0041] The cells within the biological sample may be lysed in a number of ways. For example, the cells may be lysed by heating the walls of the mixing chamber 112 which causes the cells to rupture. In some examples, the mixing chamber 112 may also include a chemical compound that lyses the cells. That is, in addition to being a volume wherein the sample is mixed with a reagent, the mixing chamber 112 may store the reagent to be used. Accordingly, during manufacture, a reagent may be deposited in the mixing chamber 112 rather than being input as part of the sample preparation operation.

[0042] In an example, a lyophilized pellet 144 (Fig. 7) contains the magnetic microparticles when it is first disposed within the mixing chamber 112. When introduced, the sample may dissolve the structure of the lyophilized pellet 144 to release the magnetic microparticles contained therein. As described above, the magnetic microparticles may be paramagnetic microparticles; in some other examples, the magnetic microparticles are paramagnetic beads.

[0043] Specifically, the magnetic microparticles may be disposed in a pellet with a dissolving membrane. Specifically, when a sample is introduced into the mixing chamber 112 it may dissolve the pellet, spilling the magnetic microparticles contained therein.

[0044] The magnetic microparticles within the pellet may be magnetic microparticles, superparamagnetic microparticles, diamagnetic microparticles, or a combination thereof, for example. As used in the present specification, the term magnetic microparticles may include microparticles that may not be magnetic in nature unless and until a magnetic field is introduced at a strength and proximity to cause them to become magnetic. The magnetic strength of the magnetic microparticles may be dependent on the magnetic field applied and may become stronger as the magnetic field is increased, or as the magnetic microparticles move closer to the magnetic source that is applying the magnetic field.

[0045] Specifically, paramagnetic microparticles may be those that have the ability to increase in magnetism when a magnetic field is present; however, paramagnetic microparticles are not magnetic when a magnetic field is not present. In some examples, the paramagnetic microparticles may exhibit no residual magnetism once the magnetic field is removed. A strength of magnetism of the paramagnetic microparticles may depend on the strength of the magnetic field, the distance between a source of the magnetic field and the paramagnetic microparticles, and a size of the paramagnetic microparticles.

[0046] Superparamagnetic microparticles may be similar to paramagnetic microparticles, however, they may exhibit magnetic susceptibility to a greater extent than paramagnetic microparticles in that the time it takes for them to become magnetized appears to be shorter. Diamagnetic microparticles may display magnetism due to a change in the orbital motion of electrons in the presence of a magnetic field.

[0047] As described above, the magnetic microparticles may be surface-activated to selectively bind with a biological component or may be bound to a biological component from a biological sample. In a specific example, an exterior of the magnetic microparticles may be surface-activated with interactive surface groups that can interact with a biological component of a biological sample or may include a covalently attached ligand.

[0048] In some examples, the ligand may include proteins, antibodies, antigens, nucleic acid primers, nucleic acid probes, amino groups, carboxyl groups, epoxy groups, tosyl groups, sulphydryl groups, or the like. In one example, the ligand may be a nucleic acid probe. The ligand may be selected to correspond with and to bind with the biological component. The ligand may vary based on the type of biological component targeted for isolation from the biological sample. For example, the ligand may include a nucleic acid probe when isolating a biological component that includes a nucleic acid sequence. In another example, the ligand may include an antibody when isolating a biological component that includes antigen.

[0049] In some examples, the magnetic microparticles can have an average particle size ranging from 10 nanometers (nm) to 50,000 nm. In yet other examples, the magnetic microparticles may have an average particle size ranging from 500 nm to 25,000 nm, from 10 nm to 1 ,000 nm, from 25,000 nm to 50,000 nm, or from 10 nm to 5,000 nm. As used in the present specification, the term “average particle size" describes a diameter or average diameter, which may vary, depending upon the morphology of the individual particle. A shape of the magnetic microparticles may be spherical, irregular spherical, rounded, semi-rounded, discoidal, angular, sub-angular, cubic, cylindrical, or any combination thereof. The shape of the magnetic microparticles may be spherical and uniform, which may be defined herein as spherical or near- spherical, e.g., having a sphericity of >0.84. Thus, any individual particles having a sphericity of <0.84 are considered non-spherical (irregularly shaped). [0050] The mixer 148 disposed within the mixing chamber 112 may stir the contents of the mixing chamber 112 to aid and expedite the lysing operation. Such mixing also places the magnetic microparticles and the nucleic acids in proximity to one another such that they may bind together. For example, the magnetic microparticles may be heavier than the solution in the mixing chamber 112 and may otherwise settle to the bottom of the mixing chamber 112. The mixer 148 introduces turbulence that distributes the magnetic microparticles more uniformly throughout the matrix of the solution such that there are more opportunities for the magnetic microparticles to bind with the nucleic acids.

[0051] The sample preparation device 100 also includes a fluid isolation chamber 314, which is a downstream component where additional operations are performed. Particularly, the fluid isolation chamber 314 is to receive the contents of the mixing chamber 112 or to perform some other sample analysis/manipulation. For example, in the fluid isolation chamber 314, the lysate may be mixed with a master mix with certain primers to carry out PCR. As another example, the sample may be concentrated and purified within the fluid isolation chamber 314. For example, the sample may be purified by a density gradient within the fluid isolation chamber 314 and magnetic motion imparted within the fluid isolation chamber 314. Furthermore, coupled to the fluid isolation chamber 314 may be liquid reagents such as master mix to further process the sample.

[0052] The sample preparation device 100 may also include an output 316 to dispense the contents of the fluid isolation chamber 314. That is, as described above, the sample preparation device 100 may prepare the sample for analysis. The output 316 of the sample preparation device 100 may eject the prepared sample onto a surface such that the analysis may be performed. In an example, the surface may be a well plate with individual wells.

[0053] Fig. 4 is an isometric cross-sectional view of a cartridge 156 with multiple sample preparation devices 100, according to an example of the principles described herein. As described above, in some examples, the host station may prepare multiple samples in parallel. For example, as described above, each sample preparation device 100 analyzes a single sample. Accordingly, multiple parallel sample preparation devices 100 allow multiple samples to be analyzed at the same time, rather than analyzing a single sample at a time.

[0054] The sample preparation devices 100 may be disposed in a cartridge 156 along with other sample preparation devices 100. The cartridge 156 is insertable into a host station, which host station provides the signals and mechanical forces to activate the mixer 148, lyse the sample, rupture the seal 158, and eject the prepared sample on to a surface.

[0055] Fig. 4 depicts the mixing chamber 112 with its associated plunger 150, seal 158, and input port 110. Fig. 4 also depicts the fluid isolation chamber 314 and the output 316. The output 316 may include an air blister. As the air blister is depressed, pressure forces the fluid out the sample preparation device 100 and onto the surface, such as a well plate.

[0056] Specific examples of the operation of the sample preparation device 100 are now provided. As a general example, a biological sample may be eluted into a transport medium. The biological sample may include a biological component of interest, such as for example nucleic acids. The biological sample may then be prepared, for example by lysing the cell which contains the biological component of interest, such as the nucleic acid, and binding the nucleic acids that are released from the cells to magnetic microparticles. The nucleic acids may then be mixed with a master mix. At this stage, the prepared sample may be ejected onto a surface, such as a titration plate where the samples may be further processed, for example by performing PCR analyses in cases where magnetic microparticles are bound to nucleic acids.

[0057] As a more specific example, a swab with a sample may be inserted into a transport vial where it is eluted into a medium. A portion of the sample is introduced, for example, via the pipette 120, into the mixing chamber 112 via the input port 110. Introduction of the sample dissolves a lyophilized pellet 144 (Fig. 7) and releases the magnetic microparticles disposed therein. The sample may be sequentially and/or simultaneously heated, via heat blocks heating walls of the mixing chamber 112 and rotation of the mixer 148. The sample is lysed by heating the sample to a temperature of 80 degrees Celsius (°C) which in one example ruptures the membrane walls for extracting nucleic acids. At this point, the nucleic acids may be cooled (e.g., natural, convection, etc.) to a temperature of around 56 °C in an example, all while mixing the sample. A chemical reaction binds a component of the lysate, such as the nucleic acids to the magnetic microparticles. Increased binding is provided via action of the mixer 148 to agitate the sample, providing greater interaction between the nucleic acids and the magnetic microparticles.

[0058] At some point prior to rupturing of the seal 158, a wash buffer may be introduced into the fluid isolation chamber 314. A wash buffer refers to a composition that may wash the magnetic microparticles of impurities that may be in the sample and that may inhibit downstream processes such as PCR. The wash buffer also forms a continual fluid path from the lysate to the output 316. Such a wash buffer may rinse the nucleic acid/magnetic microparticles, removing a reagent and preparing the sample for application of another agent. In an example, the wash buffer may include water, some salts to control pH, other salts to help keep the nucleic acids stay bound to the magnetic microparticles, a surfactant to help keep the magnetic microparticles distributed, and preservatives/biocides. In some examples, the wash buffer may include a densifier such as iodixanol to create the density gradient-based purification method in the fluid isolation chamber 314. In other examples, the wash buffer may include alcohol (ethanol or isopropanol), oils, other surfactants, etc.

[0059] In the fluid isolation chamber 314, the sample may be moved back and forth, for example, via magnetic motion to further prepare the sample. Once prepared, the sample may be ejected via the output 316 to be subsequently analyzed.

[0060] The lysate, which may be a biological sample, may then be introduced into the fluid isolation chamber 314 via action of the mixer 150 to rupture the seal 158 and the plunger 154 to drive the fluid. As described above, this motion is driven by the motor and transmitted to the mixer 150 and the plunger 154 via an actuator 118. [0061] When in the fluid isolation chamber 314, certain operations may be performed to further process the sample. Once prepared, the sample may be ejected via the output 316 to be subsequently analyzed.

[0062] T urning to Fig. 5, a flowchart illustrates a method 500 for preparing a sample with an input port seal 102, according to an example of principles described herein. Fig. 5 will be discussed with reference to Figs. 6a-d which demonstrate the input port seal 102 at various stages of the method.

[0063] As depicted in Fig. 6a, a pipette 120 is inserted into an input port 110. The input port seal 102 prevents 502 movement of the pipette 120 via contact with tapered walls of the inner tapered cone 104. This may include, for example, preventing the pipette 120 from being improperly positioned. This may further include preventing the pipette 120 from entering a volume of the mixing chamber 112. In an example, the pipette 120 tip is sealed 504 via the tapered walls to prevent leakage during sample input.

[0064] As depicted in Fig. 6b, contents of the pipette 120 are injected or otherwise released into the mixing chamber 112. This may be accomplished by a bulb of the pipette 120 being compressed by the user’s hand causing a positive displacement of fluid to leave the pipette 120. As fluid enters the mixing chamber 112, a gas, such as air within the mixing chamber 112, exits the vent 108. In other words, the sealed pipette operation includes a venting of pressure, with the pressure of the pipette 120 forcing fluid from the pipette 120 down into the mixing chamber 112, while air leaves the mixing chamber 112 through the vent 108.

[0065] Also note that if the user allows the bulb on the pipette 120 to relax, a decompression or backpressure pulls air into the bulb of the pipette 120 as the liquid is at the base of the mixing chamber 112 as depicted in Fig. 6c. With the bulb relaxed, the user may remove the pipette 120 from the input port seal 102 and input port 110. The pipette 120 is removed from the input port 110 as shown in Fig. 6d and the contents are mixed. Once again, a gas may be vented 506 as chemical reactions occur to the contents as the contents are mixed. With the pipette 120 removed, the input port seal 102 and input port 110 may be covered 508. [0066] Also note that the pipette stop 122 in the input port seal 102 prevents the pipette 120 from contacting dispensed liquid in the bottom of the mixing chamber 112. Thus, when a user allows the bulb on the pipette 120 to relax, the decompression or backpressure does not pull liquid back into the bulb of the pipette 120.

[0067] In Fig. 7, a sample preparation device 100 is shown with a lyophilized pellet 144 received into the bottom opening of the input port 110. The input port seal 102 includes an elongate channel 136 that extends downward from the bottom opening of the inner tapered cone 104. The elongate channel 136 may provide fluid to a material that is at a base of the elongate channel 136 and suspended at the opening of the input port 110. For example, a lyophilized pellet 144 shown may be retained via the input port seal 102 and the input port 110 and then wetted through fluid injected by the pipette 120.

[0068] In this example, the bottom surface of the input port seal 102 conforms to a geometry of the lyophilized pellet 144. In the case of the lyophilized pellet 144 being rounded, the bottom surface may also be rounded. Furthermore, interior surface walls of the input port 110 conform to a geometry of the lyophilized pellet 144. In the case of the lyophilized pellet 144 being rounded, the interior surface walls may also be rounded.

[0069] Lyophilized pellets 144 may come in forms that are not rounded, such as polygonal, square, diamond, and other non-rounded shapes. In an example, the lyophilized pellet 144 is a reagent that is lyophilized in situ of a plug or with a cartridge and the input port seal 102 is placed over the lyophilized plug with the opening to the mixing chamber 112 below.

[0070] The preceding description has been presented to illustrate and describe examples of the principles described. This description is not intended to be exhaustive or to limit these principles to any precise form disclosed. Many modifications and variations are possible in light of the above teaching.