TEM mesh with liquid dispersion channels

Abstract

A grid for sampling a liquid sample includes a first layer and a backing material supporting the first layer. The first layer includes a plurality of channels, each channel having a first end configured to receive a droplet of the liquid sample, a second end opposite the first end, and a length extending from the first end to the second end.

Description

Background Art

[0001] The present disclosure relates to a grid for sampling a liquid sample. The grid can be used to sample a liquid sample for transmission electron microscopy (TEM) analysis.

[0002] Typically, samples for single-particle cryo-electron microscopy are prepared by manually pipetting a buffer solution containing the protein onto a TEM grid. The grid is then blotted with filter paper and vitrified in liquid ethane. In this process, a few microliters of sample can be applied to wet the entire grid, and then 99.99% of the sample is removed. In addition, different blotting conditions (e.g., variations in blotting force and irregular patterns of fibers in the filter paper) can result in unexpected sample thickness.

[0003] Alternative sample preparation methods have been developed to eliminate the above-mentioned blotting step. In some technologies, such as piezoelectric inkjet spraying, needle printing technology and microcapillary writing, liquid distribution is controlled but very localized. Other technologies use a spray to cover the entire grid, but in these technologies, the distribution of droplet size and position and sample loss may be encountered. Summary of the invention

[0004] In one embodiment, the present disclosure provides a grid for sampling a liquid sample. The grid includes a first layer and a backing material supporting the first layer. The first layer includes a plurality of channels, each channel having a first end configured to receive a droplet of the liquid sample, a second end opposite the first end, and a length extending from the first end to the second end.

[0005] In another embodiment, the present disclosure provides a transmission electron microscope (TEM) sample preparation system including a grid and a sprayer. The above-mentioned grid is configured to sample a liquid sample. The grid includes a first layer with multiple channels and a backing material supporting the first layer, each channel having a first end configured to receive the liquid sample, a second end opposite to the first end, and a length extending from the first end to the second end. The backing material defines the bottom of each channel. The above-mentioned sprayer is configured to spray droplets of the liquid sample onto each channel so that the liquid sample spontaneously generates capillary flow.

[0006] In another embodiment, the present invention provides a method for preparing a liquid sample. The method includes: providing a grid. The grid includes a first layer having a plurality of channels and a backing material supporting the first layer, each channel having a first end configured to receive the liquid sample, a second end opposite the first end, and a length extending from the first end to the second end. The backing material defines the bottom of each channel. The method also includes: spraying droplets of the liquid sample onto the first end of each of the plurality of channels, so that the plurality of channels are filled via spontaneous capillary flow.

[0007] Other aspects of the disclosure will become apparent by consideration of the detailed description and accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 Schematic diagram of the breakdown of the grid used to sample the liquid sample.

[0009] Figure 2 for Figure 1 Schematic top view of the channel with medium grid.

[0010] Figure 3A Taken along line 4-4 Figure 2 Cross-sectional view of the middle channel.

[0011] Figure 3B is a cross-sectional view of another embodiment of a channel.

[0012] Figure 4 is a cross-sectional view of another embodiment of a channel.

[0013] Figure 5A A schematic top view of another embodiment of a channel that is a grid.

[0014] Figure 5B A schematic top view of another embodiment of a channel that is a grid.

[0015] Figure 5C A schematic top view of another embodiment of a channel that is a grid.

[0016] Figure 6 For along Figure 2 4-4 interception from the center Figure 2 A cross-sectional perspective view of the central channel.

[0017] Figure 7 Schematic diagram of the electronic control system and printer.

[0018] Figure 8 A flow chart depicting the liquid sample preparation method. DETAILED DESCRIPTION

[0019] Before explaining any embodiments of the present disclosure in detail, it should be understood that the present disclosure is not limited in its application to the details of construction and arrangement of components set forth in the following description or shown in the following drawings. The present disclosure is capable of other embodiments and can be practiced or carried out in various ways.

[0020] The present disclosure relates to a sample preparation system 10 for sampling a liquid sample 14. The sample preparation system 10 is configured to prepare the liquid sample 14 for analysis in a charged particle microscope, such as a transmission electron microscope (TEM). The illustrated application is only one example, and the sample preparation system 10 can be used in any sampling application, particularly when sampling a liquid sample 14.

[0021] like Figure 1 As shown in FIG. 3 , the sample preparation system 10 includes: a sprayer (also referred to as an inkjet printer 18) for spraying or printing a liquid sample 14 and a grid 22 for fixing the liquid sample 14. The inkjet printer 18 is configured to print a plurality of droplets 26 of the liquid sample 14 onto the grid 22. The printer can accurately print the droplets 26 so that the volume of the printed droplets is substantially the same as the volume of the portion of the grid 22 filled by the droplets 26. That is, the droplets 26 are accurately printed so that they neither overflow the grid 22 nor fail to fill the grid 22. In other embodiments, the liquid sample 14 may overflow the grid 22. In other embodiments, different devices (e.g., pipettes, capillaries, syringes, etc.) can be used to place the liquid sample 14 on the grid 22. The volume of the droplet 26 can be less than 1 nanoliter to obtain the desired film height. The printer 18 can print one droplet 26 or multiple droplets 26 onto the grid 22. The printer 18 is configured to print the droplets 26 onto the front side 34 of the grid 22. In an alternative embodiment, the printer 18 may print the droplets 26 onto the back side 38 of the grid 22. Each droplet 26 of the liquid sample 14 sprayed onto the grid 22 has a droplet size 97. In the illustrated embodiment, the droplet size 26 is approximately 23 picoliters. For example, the droplet size 97 may be in the range of 1 picoliter to 1 nanoliter. In other embodiments, the droplet size 97 may be larger or smaller.

[0022] The grid 22 includes a backing material 40 and a first layer 42. The backing material 40 can be any of a variety of different materials (e.g., a sheet, a metal, a plastic, a ceramic, a silicon nitride). The backing material 40 defines the back side 38 of the grid 22, and the first layer 42 defines the front side 34 of the grid 22. The backing material 40 and the first layer 42 are substantially the same in shape and size. In the illustrated embodiment, the backing material 40 and the first layer 42 are both circular. In alternative embodiments, the first layer 42 and the backing material 40 can be a different shape (e.g., a square, a rectangle, a trapezoid, etc.), or the first layer 42 can have a different shape from the backing material 40 (e.g., the first layer 42 can be circular, and the backing material 40 can be square).

[0023] In the illustrated embodiment, the first layer 42 is hydrophilic and the backing material 40 is hydrophilic. In alternative embodiments, the first layer 42 may not be hydrophilic and / or the backing material 40 may not be hydrophilic.

[0024] The first layer 42 includes a plurality of grooves 46. Each groove 46 defines a channel 50. The channel 50 is configured to separate each droplet 26 of the liquid sample 14 so that multiple samples can be received on the grid 22. In some embodiments, each channel 50 can receive a different sample. In other embodiments, each channel 50 can receive the same sample. For example, a first liquid sample can be placed in a first half 52 of the plurality of channels 50, and a second liquid sample can be placed in a second half 53 of the plurality of channels 50. In some embodiments, each channel 50 can receive multiple liquid samples 50. Alternatively, each of the plurality of channels 50 can receive a different liquid sample 14. In other embodiments, two or more different liquid samples 14 can be placed in a single channel 50. In some embodiments, the channel 50 can have a single inlet configured to be supplied by a single droplet 26. Alternatively, the plurality of inlets can be configured to be supplied by different droplets 26 and guide the droplets 26 to a single channel 50. As the printer 18 prints droplets 26 into each channel 50 , evaporation may be closely monitored and controlled to prevent one channel 50 from drying out before the next channel 50 is filled with the liquid sample 14 .

[0025] Relative to Figure 1In the orientation of the grid 22 shown, the first layer 42 has a left edge 54, a right edge 58, a top edge 62, and a bottom edge 66. A first axis 70 extends through the top edge 62 and the bottom edge 66. The first axis 70 may also be referred to as a longitudinal axis or a vertical axis. A second axis 74 extends through the left edge 54 and the right edge 58. The second axis 74 may also be referred to as a latitudinal axis or a horizontal axis. A solid portion 78 of the first layer 42 coincides with the latitudinal axis 74. A first group 82 of channels 50 is located above the solid portion 78, and a second group 86 of channels 50 is located below the solid portion 78. Each group 82, 86 of channels extends from the solid portion 78 toward the periphery of the first layer 42. The channels 50 are spaced apart from the periphery so that each channel 50 is completely defined by the first layer 42. The first group 82 and the second group 86 are arranged in mirror symmetry along the latitudinal axis 74. Because the first layer 42 is circular, the channels 50 closest to the left edge 54 and the channels 50 closest to the right edge 58 have a shorter length 90 than the channels 50 near the middle of the first layer 42. The length of the channels 50 increases in a direction toward the longitudinal axis 70. In the illustrated embodiment, the first layer 42 has a total of 42 channels 50 (e.g., the first group 82 has 21 channels, and the second group 86 has 21 channels). In other embodiments, the first layer 42 may have fewer or more channels 50 in total, and / or the first group 86 may have different numbers of channels 50. As described below (see Figure 5B and Figure 5C ), in some embodiments, the channels 50 may have different shapes or different patterns from each other. For example, the channels 50 may bend or radiate outward from a single entrance.

[0026] See also Figure 2 In the present embodiment, the channel 50 is linear in shape. Each of the plurality of channels 50 has a first end 98 and a second end 99. The first end 98 is configured to receive a droplet 26 from the printer 18. The second end 99 is disposed opposite the first end 98 and may be configured to receive a second droplet of the same liquid sample 50 or a second droplet of a second liquid sample. Each channel 50 also has a length 100 extending from the first end 98 to the second end 99. Each channel 50 also includes a circular portion 126 at the first end 98. The circular portion 126 is larger than the rest of the channel 50 to facilitate receiving the droplet 26. Therefore, the channel 50 defines a flow path for the liquid sample 14 from the first end 98 to the second end 99. In other embodiments, the channel 50 may not include the circular portion 126, and the droplet 26 may be directly printed into the channel 50. Alternatively, the circular portion 126 may be any of a variety of different shapes (e.g., a triangle, a square, etc.).

[0027] In some embodiments (see Figure 3A and Figure 3B), the first layer 42 can be a mesh 42A. In an alternative embodiment (see Figure 4 ), the first layer 42 may be a silicon nitride sheet 42B, and the backing material 40 may be a silicon wafer 40B on which the silicon nitride sheet 42B is suspended.

[0028] like Figure 3A As shown, mesh 42A includes multiple strips 101. Strips 101 define the sidewalls 106 of each channel 50. In the illustrated embodiment, strips 101 extend parallel to each other so that the channels are parallel to each other. Each strip 101 has a strip height 114. Strip height 114 is equivalent to the thickness 95 of the mesh. Backing material 40 is coupled to mesh 42A and defines the bottom 110 of channel 50. The illustrated backing material also defines holes 102. Holes 102 are significantly smaller than each channel 50 so that multiple holes 102 fit across the width of each channel 50. Holes 102 can be set at specific positions along channel 50 so that holes 102 do not overlap with strips 101 partially to prevent liquid sample 14 from leaking. Alternatively, backing material 40 may have a lower hydrophilicity than mesh 42A to prevent liquid sample 14 from leaking.

[0029] The mesh 42A has a mesh thickness 95, and the backing material 40 has a backing thickness 96. In the illustrated embodiment, the mesh thickness 95 is about 15 microns, and the backing thickness 96 is about 10 nanometers. For example, the mesh thickness 95 can be in the range of 5 microns to 35 microns, and the backing thickness 96 can be in the range of 5 nanometers to 50 nanometers. In other embodiments, the mesh thickness 95 and / or the backing thickness 96 can be thicker or thinner.

[0030] See also Figure 3A and Figure 3B , each strip 101 defines a sample thickness 122 of the liquid sample 14. The sample thickness 122 in this embodiment varies between each strip 101 or sidewall 106. The sample thickness 122 can vary between 1 micron and 10 microns. In other embodiments, the sample thickness 122 can have other nominal thicknesses. The sample thickness 122 varies between the sidewalls 106 because the liquid sample 14 defines a concave liquid surface in the channel 50. In other embodiments, the sample thickness 122 can be constant or convex (i.e., in the case of overfilling). Figure 3A In the embodiment shown, each strip 101 includes a ridge 124 relative to the backing material 40. The ridge 124 limits the sample thickness 122 so that the sample thickness 122 is less than the mesh thickness 95. In other embodiments, such as Figure 3BIn the embodiment shown, the strip 101 does not include the ridge 124. In this embodiment, the portion of the thickness 123 of the liquid sample 14 closest to the strip 101 is the same as the mesh thickness 95. Alternative embodiments may use different features to limit the thickness 122 of the liquid sample 14. For example, a portion of the strip 101 may be hydrophobic to limit the thickness 122.

[0031] exist Figure 4 In the illustrated embodiment, the first layer 42 is a silicon nitride sheet 42B. The sheet 42B is suspended on the silicon wafer 40B, wherein the channel 50 is etched into the sheet 42B. Specifically, the channel 50 is etched into the sheet 42B without penetrating the bottom wall 43 of the sheet 42B. The sidewall 106 can be formed while the channel 50 is etched into the sheet 42B. In some embodiments, a plurality of holes (not shown) can be etched into the bottom wall 43 of each channel 50. These holes can be close in width to each channel 50, so that each channel 50 can only fit a single hole across the width of the channel. In some embodiments, multiple holes can be etched across the width of each channel 50.

[0032] Thin slice 42B has a thin slice thickness 63, wafer 40B has a wafer thickness 64, and channel 50 has a channel thickness 65. In the illustrated embodiment, the thin slice thickness is about 350 nanometers, the wafer thickness is about 100 microns, and the channel thickness is about 300nm. Thin slice thickness 63 can be in the range of 100 nanometers to 500 nanometers, wafer thickness 64 can be in the range of 50 microns to 300 microns, and channel thickness 65 can be in the range of 100 nanometers to 500 nanometers. In other embodiments, thin slice thickness 63, wafer thickness 64 and / or channel thickness 65 can be thicker or thinner. Wafer thickness 64 is configured to be significantly larger than thin slice thickness 63, so as to provide stable support and rigidity for thin slice 42B.

[0033] In the present embodiment, channel thickness 65 can be between 100 nanometers and 500 nanometers. In this way, sample thickness 122 can vary between 100 nanometers and 500 nanometers. In other embodiments, sample thickness 122 can have other nominal thicknesses. Sample thickness 122 is different between sidewalls 106 because liquid sample 14 defines a concave liquid surface in channel 50. In other embodiments, sample thickness 122 can be constant or convex (i.e., in the case of overfilling). In the present embodiment, liquid sample 14 may overflow grid 22 due to channel thickness 65.

[0034] See also FIG. 5A to FIG. 5C , the channels 50 may have shapes different from each other. For example, the channel 50A ( Figure 5A ) can be straight, channel 50B ( Figure 5B ) can be curved 50B, or channel 50C ( Figure 5C ) may be tapered 50C. The straight channel 50A is similar to Figure 1 and Figure 2 . The straight channels 50A extend approximately parallel to each other. In an alternative embodiment, the straight channels 50A may extend transversely to each other. For example, the straight channels 50A may radiate from the central portion of the grid 22. Alternatively, some straight channels 50A may extend parallel to the longitudinal axis 70, and some straight channels 50A may extend perpendicular to the longitudinal axis 70. In an alternative embodiment, the channel 50 may branch from a single channel to become a plurality of channels. The plurality of channels may have the same width and height as the single channel, or may have a width or height different therefrom. In addition, each of the plurality of channels may have a different width or height from each other.

[0035] like Figure 5B As shown, each curved channel 50B includes a first portion 111, a second portion 112, and a third portion 113. The first portion 111 and the third portion 113 are substantially linear and parallel to each other. In an alternative embodiment, the first portion 111 and the third portion 113 may be substantially transverse. The second portion 112 is located between the first portion 111 and the third portion 113. The second portion 112 defines a bend 115, which is configured to bend and change the direction of the flow path of the liquid sample 14, so that the liquid sample 14 in the first portion 111 flows along the first flow path 116, and the liquid sample 14 in the third portion 113 flows along the second flow path 117. In some embodiments, the curved channel 50B may include one bend or multiple bends (e.g., the channel 50B may be S-shaped or zigzag).

[0036] like Figure 5C As shown, each tapered channel 50C includes a first end 98C having a first width 118 and a second end 99C having a second width 119. The first width 118 is greater than the second width 119, so that the width of the tapered channel 50C decreases from the first end 98C to the second end 99C. In the illustrated embodiment, the tapered channel 50C tapers continuously from the first end 98C to the second end 99C. More specifically, the tapered channel 50C tapers linearly from the first end 98C to the second end 99C. In other embodiments, the tapered channel 50C may taper nonlinearly and / or discontinuously between the first end 98C and the second end 99C. In an alternative embodiment, the second width 119 may be greater than the first width 118, so that the width of the channel 50C increases from the first end 98 to the second end 99.

[0037] See also Figure 6, each channel 50 has a width 130 and a height 134. The width 130 is defined by the distance between each strip 101. The height 134 is defined by the strip height 114. The width 130 and the height 134 may define any one of a plurality of aspect ratios. The aspect ratio and the hydrophilicity of the grid 22 cause the occurrence of a spontaneous capillary filling (SFC) phenomenon. In some embodiments, each channel 50 may have a width 130 and / or a height different from other channels 50. In addition, each channel 50 may have a different shape.

[0038] In order for the SFC phenomenon to occur, the aspect ratio can be lower than a critical aspect ratio, which is determined based on the contact angle between the liquid and the wall of the channel 50. For example, assuming a constant contact angle of 30 degrees, the critical aspect ratio is estimated to be 13. Alternatively, assuming a constant contact angle of 20 degrees, the critical aspect ratio is estimated to be 31. For other contact angles or non-uniform contact angles (i.e., different contact angles of the first layer 42 and the sheet 40), other critical aspect ratios are obtained. Following the principles of SFC, the droplet 26 is dispersed throughout the channel 50 until the channel 50 has a substantially constant thickness of the liquid sample 14 over the entire length of the channel 50.

[0039] See also Figure 7 , the sample preparation system 10 includes an electronic controller 138 configured to automatically or semi-automatically control the inkjet printer 30. The controller may include a programmable processor 142 (e.g., a microprocessor, a microcontroller, or another suitable programmable device) and a memory 146 (such as a non-transitory memory). The memory 146 may include, for example, a program storage area 150 and a data storage area 154. The program storage area 150 and the data storage area 154 may include a combination of different types of memory 146, such as read-only memory ("ROM"), random access memory ("RAM") (e.g., dynamic RAM ["DRAM"], synchronous DRAM ["SDRAM"], etc.), electrically erasable programmable read-only memory ("EEPROM"), flash memory, hard disk, SD card, or other suitable magnetic memory device, optical memory device, physical memory device, electronic memory device, or other data structure. The programming may be coded or learned.

[0040] As an example, the electronic controller 138 may be configured to control the movement of the printer 18. For example, the electronic controller 138 may control the rotation of the printer 18. The electronic controller 138 may also be configured to control the position or linear translation of the printer 18 in three-dimensional space, for example, to move the printer 18 to print the droplets 26 into each channel 50, which may include moving in the X direction, the Y direction, and / or the Z direction in any combination or orientation. The electronic controller 138 may also be configured to communicate with the printer 18 when the printer 18 is suitable for printing (i.e., when the printer 18 is in the correct position over the channel 50). This may be accomplished by using a sensor 158 to detect the position of the printer 18 and the corresponding channel 50. The sensor may be an optical sensor, a proximity sensor, an accelerometer, or any other similar sensor.

[0041] Figure 8 Flow chart depicting a method for preparing a liquid sample 14 for analysis by a charged particle microscope (e.g., a transmission electron microscope, a scanning electron microscope, etc.). Although the method includes specific steps, not all steps need to be performed or need to be performed in the order shown. In some embodiments, the method may include additional steps. At least some of the methods in the method may be performed by an electronic controller 138.

[0042] In step 801, the user provides a grid 22. The grid 22 includes a first layer 42 on the front side 34 and a backing material 40 on the back side 38. In an embodiment of the method, the backing material 40 is a thin sheet. The first layer 42 defines a plurality of channels 50, and the backing material 40 supports the first layer 42. Each channel 50 includes a first end 98 and a second end 99. The first end 98 is configured to receive a liquid sample 14 in a subsequent step (step 802). The second end 99 is opposite to the first end 98. The length 100 extends from the first end 98 to the second end 99. The backing material 40 defines the bottom 110 of each channel 50. The channel 50 has a height 134, a width 130, and an aspect ratio of, for example, 20. Prior to this step, the first layer 42 and the grid 22 can be aligned by a user or an alignment device (not shown) such as a microcontroller.

[0043] In step 802, droplets 26 of a liquid sample 14 are sprayed into each channel 50. The droplets 26 are injected into the first layer 42 side. The droplets 26 are further injected into the first end 98 of each channel in the plurality of channels 50. Each droplet 26 can be the same liquid sample 14, or each droplet 26 can be a different liquid sample 14. In some embodiments, spraying the droplets 26 includes: using an inkjet printer 30 to print droplets 26 of a liquid sample 14. The printer 30 can use a sensor 158 to detect the position of each channel 50. In other embodiments or methods, the printer 18 can print the droplets 26 into each channel 50 on the back side 38. In other embodiments, the droplets 26 can be sprayed by a pipette or other suitable tool. In response to the hydrophilicity and aspect ratio of the channel 50, each droplet 26 is dispersed in each channel 50 spontaneously via spontaneous capillary flow.

[0044] In step 803, the liquid sample 14 is vitrified. In some embodiments, the liquid sample 14 is vitrified by injecting the grid 22 into a bath of liquid ethane to complete the sample preparation process. The grid 22 can be injected into the bath by a user, a microcontroller, or a manipulator (e.g., tweezers, clamps, etc.). Alternatively, a jet of liquid ethane can be directed at the grid 22. In an alternative embodiment, the liquid sample 14 can be injected into a bath of a different liquid.

[0045] After completing the liquid sample preparation, the user can analyze the liquid sample using a charged particle microscope such as a TEM.

[0046] The aspect ratio and hydrophilicity of the channel 50 provide advantages. If the channel 50 has an aspect ratio that cannot cause the SCF phenomenon to occur, the liquid sample 14 may have an uneven thickness 122, or the channel 50 may not be filled at all. The aspect ratio and hydrophilicity of the channel 50 ensure that the SCF phenomenon occurs, so that the liquid sample thickness 122 is repeatable and consistent. This makes the sample thickness 122 repeatable during each sample preparation process. The evaporation of the liquid sample 14 can also be used to determine the final thickness 122. Alternatively, filter paper can be used to absorb and dilute the liquid sample 14. The filter paper can be used to absorb the entire channel 50 or only the inlet. The inkjet printer 18 further provides advantages. If a sample (such as a liquid sample 14) is injected into the grid 22 without a printer 18, sample loss may occur. Using an inkjet printer 18, sample loss is reduced by accurately printing fine droplets 26 of the liquid sample 14 into each channel 50, and its accuracy is not easy to achieve when using another tool (i.e., a pipette).

[0047] Various features and advantages of the invention are set forth in the following claims.

Claims

1. A grid for sampling a liquid sample, the grid comprising: a first layer, the first layer comprising a plurality of channels, each channel having a first end configured to receive a droplet of the liquid sample, a second end opposite the first end, and a length extending from the first end to the second end; and A backing material supports the first layer.

2. The grid of claim 1, wherein the first layer is a mesh.

3. The grid of claim 2, wherein the backing material defines the bottom of each channel.

4. The grid of claim 1, wherein the first layer is a sheet and the channels are etched into the sheet.

5. The grid of claim 1, wherein the backing material is a sheet. The grid of claim 5 , wherein the sheet comprises a plurality of holes.

7. The grid of claim 1, wherein the first layer defines ridges relative to the backing material, the ridges defining a thickness of the liquid sample.

8. The grid of claim 1, wherein the plurality of channels extend generally parallel to one another.

9. The grid of claim 1, wherein at least one channel of the plurality of channels is linear.

10. The grid of claim 1, wherein at least one channel of the plurality of channels is curved.

11. The grid of claim 1 , wherein at least one channel of the plurality of channels tapers from the first end to the second end.

12. The grid of claim 1, wherein the first layer has a thickness of 10 to 15 microns.

13. The grid of claim 1, wherein the backing material has a backing thickness of 10 nanometers to 15 nanometers.

14. The grid of claim 1, wherein the liquid sample is a first liquid sample, and wherein the second end is configured to receive a second droplet of a second liquid sample.

15. The grid of claim 14, wherein the second liquid sample is different from the first liquid sample.

16. A transmission electron microscope (TEM) sample preparation system, comprising: A grid configured for sampling a liquid sample, the grid comprising a first layer having a plurality of channels and a backing material supporting the first layer, each channel having a first end configured to receive the liquid sample, a second end opposite the first end, and a length extending from the first end to the second end, the backing material defining a bottom of each channel; as well as A sprayer is configured to spray droplets of the liquid sample onto each channel so that the liquid sample spontaneously generates capillary flow.

17. The TEM sample preparation system according to claim 16, wherein the volume of the droplet is substantially the same as the volume of the channel.

18. The TEM sample preparation system of claim 16, wherein the first layer is a thin sheet and the channel is etched into the thin sheet.

19. The TEM sample preparation system according to claim 16, wherein the first layer is a mesh.

20. The TEM sample preparation system of claim 19, wherein the mesh defines ridges relative to the backing material, the ridges defining a thickness of the liquid sample.

21. The TEM sample preparation system of claim 16, wherein the plurality of channels extend substantially parallel to each other.

22. The TEM sample preparation system according to claim 16, wherein the droplet size sprayed by the sprayer is 1 picoliter to 1 nanoliter.

23. The TEM sample preparation system according to claim 16, further comprising: An electronic controller is coupled to the sprayer to control the sprayer.

24. The TEM sample preparation system according to claim 16, wherein the sprayer is an inkjet printer.

25. The TEM sample preparation system according to claim 16, wherein the sprayer is a syringe.

26. A method for preparing a liquid sample, the method comprising: providing a grid comprising a first layer having a plurality of channels and a backing material supporting the first layer, each channel having a first end configured to receive the liquid sample, a second end opposite the first end, and a length extending from the first end to the second end, the backing material defining a bottom of each channel; as well as A droplet of the liquid sample is sprayed onto a first end of each of the plurality of channels such that the plurality of channels are filled via spontaneous capillary flow.

27. The method according to claim 26, further comprising: The liquid sample is vitrified.

28. The method of claim 26, wherein spraying the droplets comprises: Droplets of the liquid sample are printed using an inkjet printer.

29. The method of claim 26, further comprising: The liquid sample is controlled to evaporate.

30. The method of claim 26, further comprising: The liquid sample was blotted dry to control the sample thickness.

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