Optoelectronic microfluidic devices (e.g., optoelectronic tweezers (OET) devices) utilize optically induced dielectrophoresis (DEP) to manipulate objects (e.g., cells, particles, or the like) in a liquid medium.
Photoconductive material 116 is substantially resistive unless illuminated by light. While not illuminated, the impedance of the photoconductive material 116 (and thus the resistor 144 in the equivalent circuit of
A virtual electrode 132 can be created at a region 134 of the photoconductive material 116 by illuminating the region 134 with light 136. When illuminated with light 136, the photoconductive material 116 becomes electrically conductive, and the impedance of the photoconductive material 116 at the illuminated region 134 drops significantly. The illuminated impedance of the photoconductive material 116 (and thus the resistor 144 in the equivalent circuit of
Virtual electrodes like virtual electrode 132 can be selectively created and moved in any desired pattern or patterns by illuminating the photoconductive material 116 with different and moving patterns of light. Objects 108 in the medium 106 can thus be selectively manipulated (e.g., moved) in the medium 106.
Generally speaking, the unilluminated impedance of the photoconductive material 116 must be greater than the impedance of the medium 106, and the illuminated impedance of the photoconductive material 116 must be less than the impedance of the medium 106. As can be seen, the lower the impedance of the medium 106, the lower the required illuminated impedance of the photoconductive material 116. Due to such factors as the natural characteristics of typical photoconductive materials and a limit to the intensity of the light 136 that can, as a practical matter, be directed onto a region 134 of the photoconductive material 116, there is a lower limit to the illuminated impedance that can, as a practical matter, be achieved. It can thus be difficult to use a relatively low impedance medium 106 in an OET device like the OET device 100 of
U.S. Pat. No. 7,956,339 addresses the foregoing by using phototransistors in a layer like the photoconductive material 116 of
Embodiments of the present invention address the foregoing problems and/or other problems in prior art OET devices as well as provide other advantages.
In some embodiments, a microfluidic apparatus can include a circuit substrate, a chamber, a first electrode, a second electrode, a switch mechanism, and photosensitive elements. Dielectrophoresis (DEP) electrodes can be located at different locations on a surface of the circuit substrate. The chamber can be configured to contain a liquid medium on the surface of the circuit substrate. The first electrode can be in electrical contact with the medium, and the second electrode can be electrically insulated from the medium. The switch mechanisms can each be located between a different corresponding one of the DEP electrodes and the second electrode, and each switch mechanism can be switchable between an off state in which the corresponding DEP electrode is deactivated and an on state in which the corresponding DEP electrode is activated. The photosensitive elements can each be configured to provide an output signal for controlling a different corresponding one of the switch mechanisms in accordance with a beam of light directed onto the photosensitive element.
In some embodiments, a process of controlling a microfluidic device can include applying alternating current (AC) power to a first electrode and a second electrode of the microfluidic device, where the first electrode is in electrical contact with a medium in a chamber on an inner surface of a circuit substrate of the microfluidic device, and the second electrode is electrically insulated from the medium. The process can also include activating a dielectrophoresis (DEP) electrode on the inner surface of the circuit substrate, where the DEP electrode is one of a plurality of DEP electrodes on the inner surface that are in electrical contact with the medium. The DEP electrode can be activated by directing a light beam onto a photosensitive element in the circuit substrate, providing, in response to the light beam, an output signal from the photosensitive element, and switching, in response to the output signal, a switch mechanism in the circuit substrate from an off state in which the DEP electrode is deactivated to an on state in which the DEP electrode is activated.
In some embodiments, a microfluidic apparatus can include a circuit substrate and a chamber configured to contain a liquid medium disposed on an inner surface of the circuit substrate. The microfluidic apparatus can also include means for activating a dielectrophoresis (DEP) electrode at a first region of the inner surface of the circuit substrate in response to a beam of light directed onto a second region of the inner surface, where the second region is spaced apart from the first region.
This specification describes exemplary embodiments and applications of the invention. The invention, however, is not limited to these exemplary embodiments and applications or to the manner in which the exemplary embodiments and applications operate or are described herein. Moreover, the Figures may show simplified or partial views, and the dimensions of elements in the Figures may be exaggerated or otherwise not in proportion for clarity. In addition, as the terms “on,” “attached to,” or “coupled to” are used herein, one element (e.g., a material, a layer, a substrate, etc.) can be “on,” “attached to,” or “coupled to” another element regardless of whether the one element is directly on, attached, or coupled to the other element or there are one or more intervening elements between the one element and the other element. Also, directions (e.g., above, below, top, bottom, side, up, down, under, over, upper, lower, horizontal, vertical, “x,” “y,” “z,” etc.), if provided, are relative and provided solely by way of example and for ease of illustration and discussion and not by way of limitation. In addition, where reference is made to a list of elements (e.g., elements a, b, c), such reference is intended to include any one of the listed elements by itself, any combination of less than all of the listed elements, and/or a combination of all of the listed elements.
As used herein, “substantially” means sufficient to work for the intended purpose. The term “ones” means more than one.
In some embodiments of the invention, dielectrophoresis (DEP) electrodes can be defined in an optoelectronic tweezers (OET) device by switch mechanisms that connect electrically conductive terminals on an inner surface of a circuit substrate to a power electrode. The switch mechanisms can be switched between an “off” state in which the corresponding DEP electrode is not active and an “on” state in which the corresponding DEP electrode is active. The state of each switch mechanism can be controlled by a photosensitive element connected to but spaced apart from the switch mechanism.
As shown in
The first electrode 212 can be positioned in the device 200 to be in electrical contact with (and thus electrically connected to) the medium 206 in the chamber 204. In some embodiments, all or part of the first electrode 212 can be transparent to light so that light beams 250 can pass through the first electrode 212. In contrast to the first electrode 212, the second electrode 224 can be positioned in the device 200 to be electrically insulated from the medium 206 in the chamber 204. For example, as shown, the circuit substrate 216 can comprise the second electrode 224. For example, the second electrode 224 can comprise one or more metal layers on or in the circuit substrate 216. Although illustrated in
The circuit substrate 216 can comprise a material that has a relatively high electrical impedance. For example, the impedance of the circuit substrate 216 generally can be greater than the electrical impedance of the medium 206 in the chamber 204. For example, the impedance of the circuit substrate 216 can be two, three, four, five, or more times the impedance of the medium 206 in the chamber 204. In some embodiments, the circuit substrate 216 can comprise a semiconductor material, which undoped, has a relatively high electrical impedance.
As shown in
As shown in
As illustrated in
As noted above, the circuit substrate 216 can comprise electric circuit elements interconnected to form electrical circuits. As illustrated in
As shown in
In some embodiments, the impedance of the off state of the switch mechanism 246 can be two, three, four, five, ten, twenty, or more times the impedance of the on state. Also, in some embodiments, the impedance of the off state of the switch 246 can be two, three, four, five, ten, or more times the impedance of the medium 206, which can be two, three, four, five, ten, or more times the impedance of the on state of the switch mechanism 246.
Even though the switch mechanism 246 need not be photoconductive, the control module 240 can be configured such that the switch mechanism 246 is controlled by a beam of light 250. The photosensitive element 242 of each control module 240 can be a photosenstive circuit element that is activated (e.g., turned on) and deactivated (e.g., turned off) in response to a beam of light 250. Thus, for example, as shown in
In some embodiments, as shown in
The control circuitry 244 can comprise analog circuitry, digital circuitry, a digital memory and digital processor operating in accordance with machine readable instructions (e.g., software, firmware, microcode, or the like) stored in the memory, or a combination of one or more of the forgoing. In some embodiments, the control circuitry 244 can comprise one or more digital latches (not shown), which can latch a pulsed output of the photosensitive element 242 caused by a pulse of a light beam 250 directed onto the photosensitive element 242. The control circuitry 244 can thus be configured (e.g., with one or more latches) to toggle the state of the switch mechanism 246 between the off state and the on state each time a pulse of the light beam 250 is directed onto the photosensitive element 242.
For example, a first pulse of the light beam 250 on the photosensitive element 242—and thus a first pulse of a positive signal output by the photosensitive element 242—can cause the control circuitry 244 to put the switch mechanism 246 into the on state. Moreover, the control circuitry 244 can maintain the switch mechanism 246 in the on state even after the pulse of the light beam 250 is removed from the photosensitive element 242. Thereafter, the next pulse of the light beam 250 on the photosensitive element 242—and thus the next pulse of the positive signal output by the photosensitive element 242—can cause the control circuitry 244 to toggle the switch mechanism 246 to the off state. Subsequent pulses of the light beam 250 on the photosensitive element 242—and thus subsequent pulses of the positive signal output by the photosensitive element 242—can toggle the switch mechanism 246 between the off and the on states.
As another example, the control circuitry 244 can control the switch mechanism 246 in response to different patterns of pulses of the light beam 250 on the photosensitive element 242. For example, the control circuitry 244 can be configured to set the switch mechanism 246 to the off state in response to a sequence of n pulses of the light beam 250 on the photosensitive element 242 (and thus n corresponding pulses of a positive signal from the photosensitive element 242 to the control circuitry 244) having a first characteristic and set the switch mechanism 246 to the on state in response to a sequence of k pulses (and thus k corresponding pulses of a positive signal from the photosensitive element 242 to the control circuitry 244) having a second characteristic, wherein n and k can be equal or unequal integers. Examples of the first characteristic and the second characteristic can include the following: the first characteristic can be that the n pulses occur at a first frequency, and the second characteristic can be that the k pulses occur at a second frequency that is different than the first frequency. As another example, the pulses can have different widths (e.g., a short width and a long width) like, for example, Morrse Code. The first characteristic can be a particular pattern of n short and/or long width pulses of the light beam 250 that constitutes a predetermined off-state code, and the second characteristic can be a different pattern of k short and/or long width pulses of the light beam 250 that constitutes a predetermined on-state code. Indeed, the foregoing examples can be configured to switch the switch mechanism 246 between more than two states. Thus, the switch mechanism 246 can have more and/or different states than merely an on state and an off state.
As yet another example, the control circuitry 244 can be configured to control the state of the switch mechanism 246 in accordance with a characteristic of the light beam 250 (and thus the corresponding pulse of a positive signal from the photosensitive element 242 to the control circuitry 244) other than merely the presence or absence of the beam 250. For example, the control circuitry 244 can control the switch mechanism 246 in accordance with the brightness of the beam 250 (and thus the level of a corresponding pulse of a positive signal from the photosensitive element 242 to the control circuitry 244). Thus, for example, a detected brightness level of the beam 250 (and thus a level of a corresponding pulse of a positive signal from the photosensitive element 242 to the control circuitry 244) that is greater than a first threshold but less than a second threshold can cause the control circuitry 244 to set the switch mechanism 246 to the off state, and a detected brightness level of the beam 250 (and thus a level of a corresponding pulse of a positive signal from the photosensitive element 242 to the control circuitry 244) that is greater than the second threshold can cause the control circuitry 244 to set the switch mechanism 246 to the on state. In some embodiments, there can be a two, five, ten, or more times difference between the first brightness level and the second brightness level.
As still another example, the control circuitry 244 can be configured to control the state of the switch mechanism 246 in accordance with any combination of the foregoing characteristics of the light beam 250 or multiple characteristics of the light beam 250. For example, the control circuitry 244 can be configured to set the switching mechanism 246 to the off state in response to a sequence of n pulses within a particular frequency band of the light beam 250 and to the on state in response to the brightness of the light beam 250 exceeding a predetermined threshold.
The control module 240 is thus capable of controlling a DEP electrode 232 on the inner surface 218 of the circuit substrate 216 in accordance with the presence or absence of a beam of light 250, a characteristic of the light beam 250, or a characteristic of a sequence of pulses of the light beam 250 at a different region (e.g., corresponding to the location of the photosensitive element 242) of the inner surface 218, where the different region is spaced apart from the first DEP electrode 232. The photosensitive element 242, the control circuitry 244, and/or the switch element 246 are thus examples of means for activating a DEP electrode 232 at a first region (e.g., any portion of a DEP electrode 232 not disposed over a corresponding photosensitive element 242) on an inner surface (e.g., 218) of a circuit substrate (e.g., 216) in response to a beam of light (e.g., 250) directed onto a second region (e.g., corresponding to the photosensitive element 242) of the inner surface 218, where the second region is spaced apart on the inner surface 218 from the first region.
As illustrated in
The illustrations in
An input 444 of the photodiode 442 can be biased with a direct current (DC) power source (not shown). The photodiode 442 can be configured and positioned so that a light beam 250 directed at a location on the inner surface 218 that corresponds to the photodiode 442 can activate the photodiode 442, causing the photodiode 442 to conduct and thus output a positive signal to the control circuitry 244. Removing the light beam 250 can deactivate the photodiode 442, causing the photodiode 442 to stop conducting and thus output a negative signal to the control circuitry 244.
The transistor 446 can be any type of transistor, but need not be a phototransistor. For example, the transistor 446 can be a field effect transistor (FET) (e.g., a complementary metal oxide semiconductor (CMOS) transistor), a bipolar transistor, or a bi-MOS transistor.
If the transistor 446 is a FET transistor as shown in
If the transistor 446 is a bipolar transistor, the collector or emitter can be connected to the DEP electrode 232 on the inner surface 218 of the circuit substrate 216 and the other of the collector or emitter can be connected to the second electrode 224. The output of the photodiode 442 can be connected (e.g., by the control circuitry 244) to the base of the transistor 446. Alternatively, the output of the photodiode 442 can be connected directly to the base of the transistor 446. Regardless, the transistor 446 can be biased so that the signal provided to the base turns the transistor 446 off or on.
Regardless of whether the transistor 446 is a FET transistor or a bipolar transistor, the transistor 446 can function as discussed above with respect to the switch mechanism 226 of
The amplifier 546 can be any type of amplifier. For example, the amplifier 546 can be an operational amplifier, one or more transistors configured to function as an amplifier, or the like. As shown, the control circuitry 244 can utilize the output of the photodiode 442 to control the amplification level of the amplifier 546. For example, control circuitry 244 can control the amplifier 546 to function as discussed above with respect to the switch mechanism 226 of
The OET device 600 of
The control circuitry 244 can be configured to control whether the switch 604 is open or closed in accordance with the output of the photodiode 442. Alternatively, the output of the photodiode 442 can be connected directly to the switch 604. Regardless, when the switch 604 is open, the switch 604 and amplifier 602 can provide a high impedance electrical connection from the DEP electrode 232 to the second electrode 224 as discussed above. Conversely, while the switch 604 is closed, the switch 604 and amplifier 602 can provide a low impedance electrical connection from the DEP electrode 232 to the second electrode 224 as discussed above.
As shown, a color detector element 710 can comprise a plurality of color photo detectors 702, 704 (two are shown but there can be more). Each pass color detector 702, 704 can be configured to provide a positive signal to the control circuitry 244 in response to a different color of the light beam 250. For example, the photo detector 702 can be configured to provide a positive signal to the control circuitry 244 when a light beam 250 of a first color is directed onto the photo detectors 702, 704, and the photo detector 704 can be configured to provide a positive signal to the control circuitry 244 when the light beam 250 is a second color, which can be different than the first color.
As shown, each photo detector 702, 704 can comprise a color filter 706 and a photo sensitive element 708. Each filter 706 can be configured to pass only a particular color. For example, the filter 706 of the first photo detector 702 can pass substantially only a first color, and the filter 706 of the second photo detector 704 can pass substantially only a second color. The photo sensitive elements 708 can both be similar to or the same as the photo sensitive element 242 in
The configurations of the color photo detectors 702, 704 shown in
Regardless, the control circuitry 244 can be configured to set the switch mechanism 246 to one state (e.g., the on state) in response to a beam 250 pulse of the first color and to set the switch mechanism 246 to another state (e.g., the off state) in response to a beam 250 pulse of the second color. As mentioned, the color detector element 710 can comprise more than two color photo detectors 702, 704, and the control circuitry 244 can thus be configured to switch the switch mechanism 246 among more than two different states.
As shown, the indicator element 802 can be connected to the output of the control circuitry 244, which can be configured to set the indicator element 802 to different states each of which corresponds to one of the possible states of the switch mechanism 246. Thus, for example, the control circuitry 244 can turn the indicator element 802 on while the switch mechanism 246 is in the on state and turn the indicator element 802 off while the switch mechanism 246 is in the off state. In the foregoing example, the indicator element 802 can thus be on while its associated DEP electrode 232 is activated and off while the DEP electrode 232 is not activated.
The indicator element 802 can provide a visional indication (e.g., emit light 804) only when turned on. Non-limiting examples of the indicator element 802 include a light source such as a light emitting diode (which can be formed in the circuit substrate 216), a light bulb, or the like. As shown, the DEP electrode 232 can include a second opening 834 (e.g., window) for the indicator element 802. Alternatively, the indicator element 802 can be spaced away from the DEP electrode 232 and thus not covered by the DEP electrode 232, in which case, there need not be a second window 834 in the DEP electrode 232. As yet another alternative, the DEP electrode 232 can be transparent to light, which case, there need not be a second window 834 even if the DEP electrode 232 covers the indicator element 802.
As shown, each switch mechanism 246 can be configured to connect electrically a corresponding DEP electrode 232 to one of the electrodes 224, 924, 944. A switch mechanism 246 can thus be configured to selectively connect a corresponding DEP electrode 232 to the second electrode 224, a third electrode 924, or a fourth electrode 944. Each switch mechanism 246 can also be configured to disconnect the first electrode 212 from all of the electrodes 224, 924, 944.
As also shown, the power source 226 can be connected to (and thus provide power between) the first electrode 212 and the second electrode 224 as discussed above. The power source 926 can be connected to (and thus provide power between) the first electrode 212 and the third electrode 924, and the power source 946 can be connected to (and thus provide power between) the first electrode 212 and the fourth electrode 944.
Each electrode 924, 944 can be generally like the second electrode 224 as discussed above. For example, each electrode 924, 944 can be electrically insulated from the medium 206 in the channel 204. As another example, each electrode 924, 944 can be part of a metal layer on the surface 218 of or inside the circuit substrate 216. Each power source 926, 946 can be an alternating current (AC) power source like the power source 226 as discussed above.
The power sources 926, 946, however, can be configured differently than the power source 226. For example, each power source 226, 926, 946 can be configured to provide a different level of voltage and/or current. In such an example, each switch mechanism 246 can thus switch the electrical connection from a corresponding DEP electrode 232 between an “off” state in which the DEP electrode 232 is not connected to any of the electrodes 224, 924, 944 and any of multiple “on” states in which the DEP electrode 232 is connected to any one of the electrodes 224, 924, 944.
As another example of how the power sources 226, 926, 946 can be configured differently, each power source 226, 926, 946 can be configured to provide power with a different phase shift. For example, in an embodiment comprising the electrodes 224, 924 and the power sources 226, 926 (but not the electrode 944 and power source 946), the power source 926 can provide power that is approximately (e.g., plus or minus ten percent) one hundred eighty (180) degrees out of phase with the power provided by the power source 226. In such an embodiment, each switch mechanism 246 can be configured to switch between connecting a corresponding DEP electrode 232 to the second electrode 224 and the third electrode 924. The device 900 can be configured so that the corresponding DEP electrode 232 is activated (and thus turned on) while the DEP electrode 232 is connected to one of the electrodes 224, 924 (e.g., 224) and deactivated (and thus turned off) while connected to the other of the electrodes 224, 924 (e.g., 924). Such an embodiment can reduce leakage current from a DEP electrode 232 that is turned off as compared to the device 200 of
It is noted that one or more of the following can comprise examples of means for activating a DEP electrode at a first region of the inner surface of the circuit substrate in response to a beam of light directed onto a second region of the inner surface, where the second region is spaced apart from the first region; activating means further for selectively activating a plurality of DEP electrodes at first regions of the inner surface of the circuit substrate in response to beams of light directed onto second regions of the inner surface, where the each second region is spaced apart from each the first region; activating means further for activating the DEP electrode in response to the beam of light having a first characteristic, and deactivating the DEP electrode in response to the beam of light having a second characteristic; activating means further for activating the DEP electrode in response to a sequence of n pulses of the beam of light having a first characteristic; and activating means further for deactivating the DEP electrode in response to a sequence of k pulses of the beam of light having a second characteristic: the photosensitive element 242, including the photodiode 442 and/or the color detector element 710; the control circuitry 244 configured in any manner described or illustrated herein; and/or the switch mechanism 246 include the transistor 446, the amplifier 546, and/or the amplifier 602 and switch 604.
Although specific embodiments and applications of the invention have been described in this specification, these embodiments and applications are exemplary only, and many variations are possible.
This application is continuation of U.S. patent application Ser. No. 14/051,004, filed Oct. 10, 2013, which is a non-provisional (and thus claims the benefit of the filing date of) U.S. provisional patent application No. 61/724,168 filed Nov. 8, 2012, the disclosures of which are incorporated herein by reference in their entirety.
Number | Name | Date | Kind |
---|---|---|---|
6294063 | Becker et al. | Sep 2001 | B1 |
6942776 | Medoro | Sep 2005 | B2 |
6958132 | Chiou et al. | Oct 2005 | B2 |
7090759 | Seul | Aug 2006 | B1 |
7612355 | Wu et al. | Nov 2009 | B2 |
7956339 | Ohta et al. | Jun 2011 | B2 |
20050112548 | Segawa et al. | May 2005 | A1 |
20060175192 | Lin | Aug 2006 | A1 |
20090170186 | Wu et al. | Jul 2009 | A1 |
20090184331 | Omi | Jul 2009 | A1 |
20100000620 | Fouillet et al. | Jan 2010 | A1 |
20100206731 | Lau et al. | Aug 2010 | A1 |
20120024708 | Chiou et al. | Feb 2012 | A1 |
20120118740 | Garcia et al. | May 2012 | A1 |
20120325665 | Chiou et al. | Dec 2012 | A1 |
20130026040 | Cheng et al. | Jan 2013 | A1 |
20150166326 | Chapman | Jun 2015 | A1 |
Number | Date | Country |
---|---|---|
10-2010-0008222 | Jan 2010 | KR |
Entry |
---|
Fuchs et al., Electronic Sorting and Recovery of Single Live Cells from Microlitre Sized Samples, Lab Chip (Nov. 15, 2005), 6, pp. 121-126. |
Issadore et al., A Microfluidic Microprocessor: Controlling Biomimetic Containers and Cells Using Hybrid Integrated Circuit/Microfluidic Chips, Lab Chip (2010, 10, pp. 2937-2943. |
Manaresi et al., A CMOS Chip for Individual Cell Manipulation and Detection, IEEE Journal of Solid-State Circuits, vol. 38, No. 12 (Dec. 2003), pp. 2297-2305. |
International Searching Authority, The International Search Report and Written Opinion of PCT/US2013/067564, Feb. 5, 2014, 10 pages. |
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20160318038 A1 | Nov 2016 | US |
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61724168 | Nov 2012 | US |
Number | Date | Country | |
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Parent | 14051004 | Oct 2013 | US |
Child | 15207210 | US |