Microfluidic ratchets for displacing particles
10596567 ยท 2020-03-24
Assignee
Inventors
- Stefan Fringes (Schwabhausen, DE)
- Armin W. Knoll (Adliswil, CH)
- Colin Rawlings (Adliswil, CH)
- Christian Schwemmer (Zurich, CH)
- Michael Skaug (Boulder, CO, US)
Cpc classification
B01L2200/0652
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502761
PERFORMING OPERATIONS; TRANSPORTING
B03C5/024
PERFORMING OPERATIONS; TRANSPORTING
B01L2400/0415
PERFORMING OPERATIONS; TRANSPORTING
International classification
B01L3/00
PERFORMING OPERATIONS; TRANSPORTING
Abstract
Embodiments of the invention include a microfluidic device, which comprises a substrate with a channel defined therein, on an upper surface of the substrate, wherein a bottom wall of the channel comprises several contiguous steps having an asymmetric profile along a main direction of the channel, so as to form a ratchet topography. The device further comprises a lid, opposite to and at a distance from the upper surface of the substrate, so as to face the bottom wall of the channel. The bottom wall and the lid are designed to allow like sign charges to accumulate thereat, in presence of a polar liquid confined in the channel between the bottom wall and the lid, so as to allow displacement of nanoscale particles in the polar liquid, along said main direction of the channel, under application of an alternating force to said nanoscale particles, in operation of the device.
Claims
1. A microfluidic device comprising: a substrate having a first channel defined in an upper surface of the substrate, wherein a first bottom wall of the first channel comprises first contiguous steps, wherein the first contiguous steps form a first ratchet topography having an asymmetric profile along a longitudinal direction of the first channel; a lid, opposite to and at a distance from said upper surface, facing the first bottom wall of the first channel; and a second channel defined in said upper surface of the substrate, wherein a second bottom wall of the second channel comprises second contiguous steps, wherein the second contiguous steps form a second ratchet topography having an asymmetric profile along a longitudinal direction of the second channel, wherein the lid faces each of the first channel and the second channel, wherein an average depth of the second channel is larger than an average depth of the first channel, as measured in a direction perpendicular to a plane of the substrate, wherein the second channel has a lower height than the first channel.
2. The microfluidic device according to claim 1, further comprising electrodes configured to allow an alternating electric field to be applied, so as to apply a force on nanoscale particles in a polar liquid confined in the first and second channels; and wherein the first and second bottom walls and the lid are designed to allow displacement of the nanoscale particles under application of said alternating electric field, without net motion of the polar liquid.
3. The microfluidic device according to claim 1, wherein said first and second contiguous steps have a sawtooth profile.
4. The microfluidic device according to claim 3, wherein each of the first contiguous steps includes: an amplitude that is, on average, between 3 nm and 300 nm, as measured perpendicularly to the plane of the substrate; and an extension that is, on average, between 20 nm and 10,000 nm, as measured along the longitudinal direction of the first channel; and wherein each of the second contiguous steps includes: an amplitude that is, on average, between 3 nm and 300 nm, as measured perpendicularly to the plant of the substrate; and an extension that is, on average, between 20 nm and 10,0000 nm, as measured along the longitudinal direction of the second channel.
5. The microfluidic device according to claim 1, wherein a minimal gap between said first bottom wall and said lid is between 10 nm and 300 nm, said gap measured perpendicularly to the plane of the substrate; and wherein a minimal gap between said second bottom wall and said lid is between 10 nm and 300 nm, said gap measured perpendicularly to the plane of the substrate.
6. The microfluidic device according to claim 1, wherein said substrate comprises a polymer.
7. The microfluidic device according to claim 1, wherein an average width of the second channel is less than an average width of the first channel.
8. The microfluidic device according to claim 7, wherein the average width of the second channel is between 70 nm and 280 nm, while the average width of the first channel is between 500 nm and 10000 nm.
9. The microfluidic device according claim 1, further comprising two or more of said first channel and one or more second channels, each similar to said second channel, wherein each of the one or more second channels is interleaved between two of said two or more first channels that are each similar to said first channel.
10. The microfluidic device according to claim 1, further comprising two reservoirs connected to respective ends of the first and second channels.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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(8) The accompanying drawings show simplified representations of devices or parts thereof, as involved in embodiments. Technical features depicted in the drawings are not necessarily to scale. Similar or functionally similar elements in the figures have been allocated the same numeral references, unless otherwise indicated.
DETAILED DESCRIPTION
(9) In reference to
(10) Basically, the present devices 1, 1a comprise a substrate 10 with at least one channel 11, 12 defined therein. More precisely, this channel 11, 12 is defined on an upper surface 13 of the substrate 10, in a superficial thickness thereof. As for instance seen in
(11) As also seen in
(12) The bottom wall and the lid 17 are otherwise designed to allow like sign charges to accumulate at the corresponding (internal) surfaces, in presence of a polar liquid 14 (i.e., a liquid having polar molecules, exhibiting a net dipole moment, such as water). In operation, the polar liquid 14 is introduced and then confined in a ratchet channel 11, 12, between the bottom wall of the channel and the lid 17. The bottom wall and the lid typically involve dielectric materials, whose internal surfaces allow a superficial charge density, in contact with a polar liquid. Similarly, electric charges are likely to accumulate at the surface of the nanoscale particles 16, which, together with the polar liquid, form a suspension. I.e., the nanoscale particle should obviously be distinguished from molecules, atoms or ions of the polar liquid, be it because of their dimensions. The nanoscale particles 16 can typically be metallic spheres, or beads, quantum dots, bio-molecules, or beads with specific molecules bonded at their periphery, etc. In general, many types of nanoscale particles as routinely used in nanofluidic devices can be contemplated for the present purpose.
(13) As we shall see, the formation of superficial charges and the energy landscape allow displacement of nanoscale particles 16 in the polar liquid 14, along a main direction x of the channel 11, 12, under application of an alternating force to such particles 16. The main direction of the channel 11, 12 can be regarded as a longitudinal direction of this channel, although the channel need not necessarily be formed as a straight channel.
(14) The steps of the channel 11, 12 extend, one after the other, along the longitudinal direction x of the channel. In simple implementations (such as in
(15) The asymmetric steps may for instance have a sawtooth profile, which may be compared with a sawtooth wave or saw wave, bearing resemblance with teeth of a plain-toothed saw although the rake angle of the saw is not necessarily zero here (merely because of the fabrication processes available). The depth a of a step corresponds to the amplitude of the sawtooth wave profile in that case, as illustrated in
(16) Still, other asymmetric profiles may be contemplated. In all cases, the steps will exhibit at least two distinct slopes, i.e., with at least one slope in each direction (x and x), where the slopes differ (in absolute values). In
(17) Present Inventors have discovered that accurate, asymmetric steps could be repeatedly fabricated with nanometer-range depths. I.e., lithographically patterned 3D topographies allow 2D energy landscapes to be achieved for nanoparticles, where the complexity of the landscapes exceeds mere recess geometries. This way, clean ratchet topographies can be obtained, which allow sufficiently strong potential landscapes, whose confinement energies (at each step) are typically between 2 and 10 k.sub.BT, and typically on the order of 5 k.sub.BT. That is, in embodiments, the contiguous steps 110, 120 are designed so as to result in a static energy landscape, according to which said particles 16 are confined in the steps 110, 120 if no alternating force is applied, and wherein confinement energies of the contiguous steps are, on average, between 2 and 10 k.sub.BT for each step.
(18) The present devices 1, 1a can for instance be obtained by thermal scanning probe lithography (or tSPL for short), which has recently demonstrated absolute depth accuracy in the nanometer range. The substrate may for instance comprise a thermally sensitive polymer, such as polyphthalaldehyde (PPA). Yet, other materials can be contemplated. In particular, a pattern as initially obtained (e.g., by thermally patterning PPA), may be transferred to other materials, e.g., using dry etching. In general, suitable materials are materials such as oxides, which spontaneously charge in contact with water or other polar liquids. Examples of suitable materials are silicon oxide and aluminum oxide, which negatively and positively charge, respectively, under intermediate pH conditions. Also, the top surface (lid) will likely be made from a material having similar properties (like glass or oxides). This way, like sign charged surfaces can be achieved.
(19) The resulting devices allow rocking Brownian motors to be achieved, by applying an alternating force to the nanoparticles, at which superficial charges accumulate too. Such forces may for example originate from an alternating electric field or, more generally, an alternating electro-magnetic optical field (also called optical field), or, still, an alternating liquid flow, applied along the channel (although no net fluid motion need be involved).
(20) As it may be realized, two or more of these types of alternating fields may be combined. As it may further be realized, like charged surfaces are needed, in order to be able to generate an asymmetric static energy landscape for the particles and, this, irrespective of the type of field applied. In operation, a polar liquid 14 containing the particles 16 is confined in the channel 11, 12, between the lower wall (as defined in the substrate 10) and the upper lid 17 (whose lower surface provides an upper confinement wall), at which like sign charges accumulate. Adequate liquids will typically have a dielectric constant of more than 10 at room temperature, to be considered to be polar enough. Still, liquid with higher dielectric constant can be used, such as water. The interplay between the modulated lower wall and the upper wall (lid) 17 is what makes it possible to obtain the desired energy landscape.
(21) The rocking Brownian motor accordingly obtained may notably be used to move nanoparticles along the ratchets and, in particular, to efficiently sort nanometric particles of different sizes, as discussed below in detail, in reference to
(22) Referring now more particularly to
(23) As seen in
(24) The electric field is typically applied via a controller 30. Yet, the controller 30 need not necessarily be part of the microfluidic device 1, 1a. Indeed, the device 1, 1a is a microfabricated device, which makes it difficult (though not impossible) to integrate such a controller. Rather, this controller 30 will typically be coupled to the device 1, 1a, to form a microfluidic system, as described latter in detail.
(25) As illustrated in
(26) The steps 110, 120 can form a periodic structure of steps, along the main direction x of their respective channel 11, 12. That is, each of the contiguous steps has, in a same channel, essentially a same amplitude, same slopes and a same extension, subject to tolerances allowed by the fabrication process used (e.g., tSPL, as in some embodiments). This mitigates erratic behaviors of the particles as they are being displaced through the channels and makes the system more predictable. It should be noted that present ratchets typically involves at least 10 or 15 contiguous steps, as opposed to a few geometric recesses. Yet, many more steps may be achieved, e.g., more than 20, 30, 50 or even 100, following the same principles, in embodiments. For instance, present inventors have obtained ratchets of hundreds of identical steps, subject to 1-3 nm deviations.
(27) As evoked earlier, an important parameter is the distance between the lid 17 and the bottom wall of the channel 11, 12. In that respect, referring back to
(28) The steps 110, 120 of the channels 11, 12 modulate the effective gap between the bottom wall and the lid and the amplitude of this modulation will, in practice, typically be on the order of the Debye length of the liquid 14 (e.g., 3 to 300 nm). On the other hand, the total, effective distance between the bottom wall and the lid, typically has to be the size of the particle plus 2 to 6 times the Debye length, to achieve efficient particle motions.
(29) As an example of implementation, using Debye lengths of less than 20 nm, present inventors have achieved energy landscapes of up to 10 k.sub.BT in scale at a lateral resolution of less than 100 nm. They have notably obtained nanofluidic rocking Brownian motors for gold nano-spheres of 60 nm diameter, which particles allow for high spatio-temporal resolution (using optical microscopy), revealing all relevant physical system parameters such as the 10 nm spatially resolved particle interaction potential (in this example) and the millisecond resolved particle motion in-situ.
(30) For instance, gold particles in electrolyte (Debye length k.sup.1=153 nm) were confined in a nanofluidic slit of modulated gap distance (as in
(31) Note that there is a competition between the electrophoretic force F.sub.el, due to the electric field E on the charged particle, and the electro-osmotic force F.sub.eo, due to the electric field on counter ions, which induces a fluid flow that, in turn, generates a force on a particle due to Stokes drag. For negatively charged particles F.sub.el acts in the opposite direction of the electric field while F.sub.eo acts in the direction of the electric field. The present Inventors have repeatedly observed, experimentally, that particles move toward the negative electrode, that is, in the direction of the electric field direction, and thus concluded that F.sub.eo>F.sub.el.
(32) Amongst other applications, present Inventors have demonstrated the possibility to drive particles along strongly curved guiding paths, as well as sorting of 60 and 100 nm particles into opposite directions, within seconds, using distinct types of ratchets. The latter aspect is now discussed in detail, in reference to
(33) In embodiments such as depicted in
(34) The lid 17 faces each of the first channel 11 and the second channel 12, which extend contiguously, so as to form a pair of contiguous channels 11, 12. The channels 11, 12 allow fluid communication, such that particles 16 in one of the contiguous channels 11, 12 can pass in the contiguous channel, in operation.
(35) Importantly, the average depth of the second channel 12 is larger than the average depth of the first channel 11, as measured along axis z, i.e., perpendicularly to the average plane of the substrate 10. Thus, the second channel is recessed from the first channel, as better seen in
(36) As said above, the asymmetric profiles of the contiguous channels 11, 12 are designed so as to allow opposite displacements of the particles in the two types of channels. I.e., the displacement of particles in the second channel 12 will, on average, be opposite to the displacement of particles in the first channel, under application of an alternating force.
(37) More generally, we note that the present devices 1a may comprise one, or two, or more second channels 12, wherein the second channels 12 are interleaved between, i.e., interdigitated with channels 11 of the first type. Fluid communication (from the top) between the channels make sure that particles in a given one of the channels 11, 12 can pass in a contiguous channel. One may thus have several pairs of channels 11, 12, where the pairs extend contiguously, as assumed in
(38) We note that, contrary to the amplitude a of each step (measured peak-to-peak, like an amplitude), the average depths r.sub.1, r.sub.2 (see
(39) Referring back to the example of
(40) Nanoparticles of different size are dispersed in a polar liquid (e.g., water or any other high dielectric constant liquid) and, before the sorting, can be found randomly distributed over the landscape created by topography and confinement, since all surfaces involved will have a same sign charge, in operation.
(41) Due to the different depth of the two ratchets, the probability distribution along the vertical perpendicular axis depends on the particle size. Larger particles 16b (with more surface charge and less distance to the confining surfaces) are most likely to be found in the deeper written ratchet 12 because the energy penalty of leaving this ratchet 12 is higher. In contrast, smaller particles 16a (with less surface charge can also be found within the shallow ratchet 11 with a reasonable probability).
(42) The probability to find a small particle 16a outside the deeper ratchet 12 can be tuned by adapting the width of the ratchets 11, 12 along the y-axis. Thus, in order to get a sufficiently high probability of finding small particles outside the second (deeper) ratchet 12, the width of the latter (as measured along the y-axis) can be less than (and likely small in comparison to) the width of the first ratchets 11. For example, in embodiments, the average width of the second channel 12 is between 70 nm and 280 nm, while the average width of the first channel 11 is between 500 nm and 10 000 nm.
(43) This is illustrated in
(44) In operation, an alternating (i.e., oscillating) force is switched on to bring the whole system out of equilibrium, as illustrated in
(45) For example, referring back to the previous example of 60 nm and 100 nm in a device 1a such a depicted in
(46) Beyond this example, experiments conducted by the present Inventors led them to conclude that a reasonable average depth of the deeper ratchets 12 should typically be between 30 nm and 300 nm, while the average depth of the shallower ratchets 11 can be of at least 20 nm. These average depths are measured with respect to the upper (free) surface 13 of the substrate 10.
(47) As said earlier, the depths of the steps 110, 120 in the channels 11, 12 result in a modulation of the gap distance between the bottom wall and the upper wall 17, whose amplitude a need typically be, in practice, on the order of the Debye length (e.g., 3 to 300 nm), whereas the total gap distance d+r typically has to be the size of the particle plus 2 to 6 times the Debye length. The second ratchets are deeper than the first's, the difference being on the order of the Debye length or less. The height difference results in an energy barrier and need be carefully refined. Else, if the step is too big, smaller particles 16a will also be confined to the second ratchet.
(48) As evoked earlier, the present invention may further be embodied as a microfluidic system, i.e., a system that comprises a microfluidic device 1, la as described herein, and, in addition, a voltage controller 30. The controller is adapted for applying a voltage to electrodes 15 in the device 1, 1a, as for instance depicted in
(49) If necessary, the voltage controller 30 may be adapted for applying a rotating voltage to at least three electrodes 15. For example, a rotating voltage of 3V may be applied, which has an oscillating frequency of 30 Hz. In exemplary embodiments, four electrodes may be used in combination with square waves applied with a 90 degree phase shift.
(50) In accordance with a further aspect, the present invention can further be embodied as a method for displacing or sorting particles 16, 16a, 16b in a microfluidic device 1, 1a such as described above, as illustrated in
(51) Essential aspects of such methods have already been described. They generally rely on a microfluidic device 1, 1a, provided with particles 16, 16a, 16b in a polar liquid 14 that is confined in the channel(s) 11, 12 of the device 1, 1a. In addition, and as described earlier, an alternating force need be applied to particles in the liquid 14, so as to displace the particles along a main direction (x, or x) of the channel(s) 11, 12. An alternating electric field can be applied, e.g., based at least in part on a voltage controller as in
(52) Such a method is advantageously implemented in a device 1a such as depicted in
(53) While the present invention has been described with reference to a limited number of embodiments, variants and the accompanying drawings, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the scope of the present invention. In particular, a feature (device-like or method-like) recited in a given embodiment, variant or shown in a drawing may be combined with or replace another feature in another embodiment, variant or drawing, without departing from the scope of the present invention. Various combinations of the features described in respect of any of the above embodiments or variants may accordingly be contemplated, that remain within the scope of the appended claims. In addition, many minor modifications may be made to adapt a particular situation or material to the teachings of the present invention without departing from its scope. Therefore, it is intended that the present invention not be limited to the particular embodiments disclosed, but that the present invention will include all embodiments falling within the scope of the appended claims. In addition, many other variants than explicitly touched above can be contemplated. For example, other materials than those explicitly mentioned may be contemplated, be it in respect of the substrate 10, the lid 17, or the particles 16, 16a, 16b.