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Title:
PARTICLE TRANSPORT AND CHARACTERISATION
Document Type and Number:
WIPO Patent Application WO/2008/075053
Kind Code:
A3
Abstract:
A liquid crystal device is disclosed with a layer of liquid crystal, at least one non-liquid-crystal particle (e.g. nano scale) held in the liquid crystal and a substrate on which an array of electrodes is formed. The device is operable to apply a desired potential to each electrode. The potential applied to each electrode is controllable to affect the director of at least a region of the liquid crystal layer local to each said electrode and thereby to form at least one disclination in the liquid crystal layer. The device is also adapted to controllably move the particle due to an interaction between the particle and the disclination and by control of the potential applied to said electrodes to control the disclination.

Inventors:
CROSSLAND WILLIAM ALDEN (GB)
CLAPP TERRY VICTOR (GB)
Application Number:
PCT/GB2007/004898
Publication Date:
October 23, 2008
Filing Date:
December 19, 2007
Export Citation:
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Assignee:
CAMBRIDGE ENTPR LTD (GB)
CROSSLAND WILLIAM ALDEN (GB)
CLAPP TERRY VICTOR (GB)
International Classes:
B01L3/00; F04B19/00; F04D33/00
Domestic Patent References:
WO2003045556A22003-06-05
Foreign References:
US20050221271A12005-10-06
US20040159546A12004-08-19
US20010026778A12001-10-04
Other References:
LEE S ET AL: "Dynamic behavior of silica particles in liquid crystals under an AC applied voltage", DIELECTRIC LIQUIDS, 1999. (ICDL '99). PROCEEDINGS OF THE 1999 IEEE 13TH INTERNATIONAL CONFERENCE ON NARA, JAPAN 20-25 JULY 1999, PISCATAWAY, NJ, USA,IEEE, US, 20 July 1999 (1999-07-20), pages 571 - 574, XP010354581, ISBN: 0-7803-4759-5
YOSHITAKA MIEDA ET AL: "Micromanipulation Method using Backflow Effect of Liquid Crystals", MICRO-NANOMECHATRONICS AND HUMAN SCIENCE, 2006 INTERNATIONAL SYMPOSIUM ON, IEEE, PI, November 2006 (2006-11-01), pages 1 - 6, XP031052004, ISBN: 1-4244-0717-6
MIEDA YOSHITAKA ET AL: "Two-dimensional micromanipulation using liquid crystals", APPLIED PHYSICS LETTERS, AIP, AMERICAN INSTITUTE OF PHYSICS, MELVILLE, NY, US, vol. 86, no. 10, 28 February 2005 (2005-02-28), pages 101901 - 101901, XP012064502, ISSN: 0003-6951
ZHONG ZOU ET AL.: "Pumping liquid crystals", PHYSICAL REVIW LETTERS, vol. 75, no. 9, 28 August 1995 (1995-08-28), pages 1799 - 1803, XP002475204
DIERKING ET AL.: "Electromigration of microspheres in nematic liquid crystals", PHYSICAL REVIEW E, vol. 73, 4 January 2006 (2006-01-04), pages 011702-1 - 011702-6, XP002475205
KWOK H S ET AL: "Liquid crystal on silicon microdisplays", SOLID-STATE AND INTEGRATED CIRCUITS TECHNOLOGY, 2004. PROCEEDINGS. 7TH INTERNATIONAL CONFERENCE ON BEIJING, CHINA 18-21 OCT. 2004, PISCATAWAY, NJ, USA,IEEE, US, vol. 3, 18 October 2004 (2004-10-18), pages 1987 - 1990, XP010805562, ISBN: 978-0-7803-8511-5
UNDERWOOD ET AL: "A review of microdisplay technologies", 20001121; 20001121 - 20001123, 21 November 2000 (2000-11-21), XP002272068
Attorney, Agent or Firm:
NAYLOR, Matthew et al. (York House23 Kingsway,London, Greater London WC2B 6HP, GB)
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Claims:

CLAIMS

1. A liquid crystal device having: a layer of liquid crystal; at least one non-liquid-crystal particle held in the liquid crystal; a substrate on which an array of electrodes is formed, wherein the device is operable to apply a desired potential to each said electrode, and the potential applied to each electrode is controllable to affect the director of at least a region of the liquid crystal layer local to each said electrode and thereby to form at least one disclination in the liquid crystal layer, the device being adapted to controllably move the at least one particle due to an interaction between the particle and said at least one disclination and by control of the potential applied to said electrodes to control said disclination.

2. A device according to claim 1 wherein the particle has at least one dimension of at least 10 nanometres.

3. A device according to claim 1 or claim 2 wherein the particle has a maximum dimension of at most 10 microns.

4. A device according to any one of claims 1 to 3 wherein the thickness of the liquid crystal layer is at least 10 microns .

5. A device according to any one of claims 1 to 4 wherein the liquid crystal is a thermotropic liquid crystal.

6. A device according to claim 5 wherein the liquid crystal is a nematic liquid crystal.

7. A device according to any one of claims 1 to 6 including a cover member for defining a space for the layer of liquid crystal between the substrate and the cover member, the cover member further including at least one electrode opposing the array of electrodes of the substrate.

8. A device according to any one of claims 1 to 6 wherein electrode array of the substrate includes laterally-opposed electrodes, so that the necessary electric field distribution is formed by placing adjacent electrodes at different potentials .

9. A device according to any one of claims 1 to 8 wherein the at least one disclination is formed by an electric field strength of at least 0.1 V per micron.

10. A device according to any one of claims 1 to 9 wherein the at least one disclination is formed by an electric field strength of 100 V per micron or less.

11. A device according to any one of claims 1 to 10 wherein the disclination is formed by applying the voltage with a switch-on speed (or switch-off speed) in the kHz range.

12. A device according to any one of claims 1 to 11 wherein, in use, a series of disclinations is formed.

13. A device according to any one of claims 1 to 12 based on a LCOS architecture substrate.

14. A device according to any one of claims 1 to 13 wherein the liquid crystal layer has a net flow when the director of the liquid crystal is aligned.

15. A device according to any one of claims 1 to 14 having at least one flow path defined by a conduit along the device, the conduit at least partly locating said layer of liquid crystal.

16. A device according to claim 15 having subsidiary transport paths connected at one or more branches with a main transport path.

17. A device according to claim 16 including a port for introducing the particle or particles into one or more transport paths of the device.

18. A device according to any one of claims 1 to 17 further including an array of optical elements for detecting a pattern of disruption of the director field of the liquid crystal surrounding the particle or particles.

19. A method of controlling the movement of at least one particle in a liquid crystal device, the device including: a layer of liquid crystal; at least one non-liquid-crystal particle held in the liquid crystal; and a substrate on which an array of electrodes is formed, the method including: controlling the potential applied to each said electrode to affect the director of at least a region of the liquid crystal layer local to each said electrode and thereby to form at least one disclination in the liquid crystal layer, and controllably moving the at least one particle due to an interaction between the particle and said at least one disclination and by control of the potential applied to said electrodes to control said disclination.

20. A method according to claim 19 including forming a time- varying array of one or more disclinations by providing a suitable time-varying electric field distribution.

21. A method according to claim 20 wherein the disclinations are provided in a moving series, and the particle is moved along by more than one of the series of moving disclinations, so that the particle is successively swept along by the series of disclinations.

22. A method according to any one of claims 19 to 21 wherein the electric field applied to a portion of the liquid crystal layer is be varied with time so that, for the particle entrained in the liquid crystal layer, a rapid alignment of the director causes a relatively large movement of the particle, and a slow de-alignment of the director causes only a small reverse movement of the particle to result in a net movement of the particle over a cycle of varying electric field.

23. A method according to any one of claims 19 to 22 further including the step of detecting the location of the particle by its interaction with local liquid crystal molecules using a resulting effect on the director field of the liquid crystal surrounding the particle.

24. A method according to claim 23 wherein the location of the particle is detected using polarised light microscopy.

25. A method according to claim 23 wherein the location of the particle is detected using an array of optical elements in the device.

26. A method according to any one of claims 23 to 25 wherein the location of the particle is detected during movement of the particle, so that the path of the particle is tracked.

27. A liquid crystal device having: a layer of liquid crystal; a non-liquid-crystal particle held in the liquid crystal; a substrate on which, at an analytical station, one or more functional analytical electronic components are formed, wherein the device is operable so that, when the particle is located at the analytical station, said one or more functional analytical electronic components are operable to carry out an analytical operation on the particle.

28. A method of analysing a particle held in a liquid crystal device, the device having: a layer of liquid crystal; a non-liquid-crystal particle held in the liquid crystal;

a substrate on which, at an analytical station, one or more functional analytical electronic components are formed, the method including the step of operating said one or more functional analytical electronic components to carry out an analytical operation on the particle.

29. An analytical device having a plurality of analytical stations formed on a LCOS backplane, each analytical station being adapted to receive at least one particle on which at least one analytical operation is to be carried out.

30. A device according to claim 29 having a transport mechanism for transporting said particles (analyte particles) and, optionally, for transporting other species (e.g. reagents), to and/or from said analytical stations.

31. A device according to claim 29 or claim 30 including a layer of liquid crystal formed above the analytical stations, the layer of liquid crystal providing one or more transport pathways .

Description:

PARTICLE TRANSPORT AND CHARACTERISATION

The present invention relates to devices for transporting particles, particularly but not exclusively nanoscale particles. The invention also relates to methods for transporting such particles. In other aspects, the invention also relates to methods and devices for characterising and/or tracking such particles.

The use of liquid crystals in display devices is well known. For example, a colour liquid crystal display (LCD) has an array of transmissive liquid crystal pixels, each subdivided into red, green and blue sub-pixels, and each sub-pixel being capable of being switched between a transmissive and a non- transmissive state and to intermediate (greyscale) states. A conventional LCD uses a layer of twisted nematic liquid crystal molecules that twist and untwist in response to an applied voltage in order to affect the polarisation direction of light passing through the liquid crystal layer, and hence the transmission or absorption of the light at a polarising filter disposed above the liquid crystal layer.

Since it is impractical to provide individual wiring for each sub-pixel in a display, the sub-pixels are arranged in rows and columns, so that an individual sub-pixel can be addressed

by a suitable signal applied to its row and column. Each sub- pixel is provided with a transparent thin film transistor (TFT) so that the required sub-pixel can be switched on without changing the state of the other sub-pixels in the same row and the same column. This also improves the efficiency of the display. The display uses a glass substrate. A similar approach is taken for LCD transmission projectors, except that the sub-pixels are typically much smaller than the sub-pixels of the display.

An interesting application of TFT technology is set out in ,WO 03/045556. This document discloses an active matrix microfluidic platform employing a TFT matrix in order to manipulate small samples of fluid held in a space between the TFT matrix and an upper cover. In effect, the small samples of fluid and an immiscible carrier fluid sit in the space that would normally be filled with liquid crystal (but which is not filled with liquid crystal in WO 03/045556) . The motion of the fluid samples is initiated and controlled by electrowetting, by operation of the drive electrodes of the

TFTs to change the contact angle between the fluid samples and a dielectric layer between the samples and the TFT electrodes. The resulting unbalanced forces on the sample cause movement of the sample.

An alternative to transmission LCD displays is liquid crystal over silicon (LCOS) technology, which relies on reflection rather than on transmission in order to provide an image. Such devices find particular use in projection television applications. A typical LCOS device has a silicon substrate with suitable integrated circuitry to provide control electronics for an array of pixels. A reflective layer (typically aluminium) is provided over the control electronics. A layer of liquid crystal above the reflective layer is controlled in a similar manner to a conventional LCD, to allow each pixel to be controlled to reflect or absorb incident light.

The use of a reflective architecture allows the use of a silicon (or other semiconductor) substrate. This means that conventional silicon processing techniques can be used to provide the electronic components for each pixel, and so the pixel size can be made extremely small. In turn, this allows the formation of very large numbers of pixels on a chip of modest size. A typical LCOS chip size is around 0.7 inch (about 18 mm) across and can carry 1920 x 1080 pixels. Additionally, since the light need not pass through the control electronics, it is possible for LCOS devices to operate efficiently. The addressing of each pixel in a LCOS device is similar to the row-column addressing in a conventional TFT LCD.

A typical LCOS chip has a liquid crystal layer thickness of around 1-5 microns.

It is usual for LCOS chips to be formed using CMOS

(complementary metal-oxide-semiconductor) technology. This allows the formation of very dense arrays of the required electronic components for controlling the pixels, and thus allows the formation of very dense arrays of pixels. LCOS chips can be formed using a modern 90 nanometer process, for example, or other deep sub-micron silicon CMOS technology.

It is known that topological defects can form in liquid crystal layers . These are line defects and are known as disclinations . Disclinations can be considered to be line discontinuities in the director structure of the liquid crystal layer. They have the effect of scattering or depolarising light and so are considered to be detrimental to the performance of liquid crystal display devices, including LCOS devices. The reader is referred to "Liquid Crystals" by S. Chandrasekhar (Cambridge Monographs in Physics, Cambridge University Press 14 July 1977, ISBN 0521211492) for further background on the nature and formation of disclinations.

The present inventors have investigated aspects of liquid crystal behaviour in LCOS structures. In a first development,

the present inventors have found that it is possible to controllably move particles held in a liquid crystal layer by suitable operation of control electrodes to affect the average orientation of the liquid crystal molecules.

In one aspect of this first development, the present invention provides a liquid crystal device having: a layer of liquid crystal; a non-liquid-crystal particle held in the liquid crystal; a substrate on which an array of electrodes is formed, wherein the device is operable to apply a desired potential to each said electrode, and the potential applied to each electrode is controllable to affect the director of at least a region of the liquid crystal layer local to each said electrode, the device being adapted to controllably move the particle by control of the potential applied to said electrodes .

In another aspect of this first development, the present invention provides a method of controlling the movement of a particle in a liquid crystal device, the device including: a layer of liquid crystal; a non-liquid-crystal particle held in the liquid crystal; and a substrate on which an array of electrodes is formed, the method including:

controlling the potential applied to each electrode to affect the director of at least a region of the liquid crystal layer local to each said electrode thereby to controllably move the particle.

The invention provides a particularly useful effect by transporting particles in a closed environment in a controlled manner. The nature of the particles (as discussed below) depends on the application for which the device is used, but the invention has applicability to biological particles (such as cells (prokaryotic and/or eukaryotic) , viruses, virus particles (virions), prions, viroids, proteins, DNA strands, and derivatives and equivalents thereof) , organic particles (e.g. polymer or oligomer particles), inorganic particles (e.g. nanotubes, buckyballs, etc.), metallic particles and composite particles. It is not necessary that the particles are solid, but it is preferred that the particles are discrete. If the particles are liquid (or part-liquid) particles, it is strongly preferred that the particles retain their identity (i.e. do not intimately mix with the liquid crystal molecules) at least during transport of the particles within the device. It is preferred of course that the particles do not chemically react with the liquid crystal molecules .

In certain circumstances, it is possible to achieve movement of the particle not only via translation of the particle but also via rotation of the particle. This is possible, for example, if the particle is asymmetric in shape and/or polarisability, so that it can be moved with the liquid crystal director field.

It is preferred that the transport of a particle along a liquid crystal conduit is utilised in order to bring the particle to a desired location on the device in order to perform a specific operation at that location. Such an operation may for example be an analytical operation utilising, for example, an optical detector. This is particularly useful if the particle is labelled with a fluorescent tag. Other analytical operations include voltammetric analysis, e.g. full electrochemical cyclic voltammetry. These operations are made possible in liquid crystal on semiconductor devices due to the possibility of forming functional electronic components (such as optical detectors, digital-to-analogue and/or analogue-to-digital converters) integrally and at high density, e.g. using CMOS technology, in the substrate of the device.

Particular analytical operations that can be performed are described in: P. Migliorato et al, "Label-free detection of DNA single base pair mismatch reported with a field effect

device" (1st International TFT Conference, Seoul, Korea, 2005) ; P. Migliorato et al, "Biologically Sensitive Field Effect Devices using Polysilicon TFTs" (1st International TFT Conference, Seoul, Korea, March 2005), the contents of which documents are hereby incorporated by reference in their entirety.

Indeed, it is considered that the provision of at least one analytical station for carrying out an analysis on a particle in a liquid crystal device is an independent, second development of the present invention. Accordingly, in one aspect of this second development, there is provided a liquid crystal device having: a layer of liquid crystal; a non-liquid-crystal particle held in the liquid crystal; a substrate on which, at an analytical station, one or more functional analytical electronic components are formed, wherein the device is operable so that, when the particle is located at the analytical station, said one or more functional analytical electronic components are operable to carry out an analytical operation on the particle.

In another aspect of this second development, there is provided a method of analysing a particle held in a liquid crystal device, the device having:

a layer of liquid crystal; a non-liquid-crystal particle held in the liquid crystal; a substrate on which, at an analytical station, one or more functional analytical electronic components are formed, the method including the step of operating said one or more functional analytical electronic components to carry out an analytical operation on the particle.

In a third development of the present invention, the present inventors have realised an important practical issue, that known technology used to produce LCOS devices, and related CMOS technology, provides a platform on which new analytical technologies can be built at a scale and efficiency that would be in practice impossible in the absence of such a platform.

Accordingly, in one aspect of this third development, the present invention provides an analytical device having a plurality of analytical stations formed on a LCOS backplane, each analytical station being adapted to receive at least one particle on which at least one analytical operation is to be carried out.

Preferably the device is a lab-on-a-chip. In such devices, it is preferred to provide a transport mechanism for transporting said particles (analyte particles) and, optionally, for

transporting other species (e.g. reagents), to and/or from said analytical stations.

Preferably, the device includes a layer of liquid crystal formed above the analytical stations, the layer of liquid crystal providing one or more transport pathways.

Any of the aspects of the first, second and/or third developments can be combined in any combination, unless the context demands otherwise. The following preferred features are applicable to any of these aspects, singly or in any combination, unless the context demands otherwise.

Preferably, the particle has at least one dimension of at least 10 nanometres. More preferably, the particle has at least one dimension that is at least 15 nm, at least 20 ran, at least 25 nm, at least 30 nm, at least 35 nm, at least 40 nm, at least 45 nm, at least 50 nm, at least 55 nm, at least 60 nm, at least 65 nm, at least 70 nm, at least 75 nm, at least 80 nm, at least 85 nm, at least 90 nm, at least 95 nm, or at least 100 nm. The upper size limit of the particle depends to some extent on the nature of the particle and its interaction with the liquid crystal molecules and the movement mechanism being utilised in the device, but preferably the particle has a maximum dimension of 10 microns. Preferably, the particle is 9 microns or less, 8 microns or less, 7

microns or less, 6 microns or less, 5 microns or less,

4 microns or less, 3 microns or less, or 2 microns or less.

Preferably, the thickness of the liquid crystal layer is at least 10 microns. The thickness may be higher, e.g. at least 15 or at least 20 microns. This is significantly thicker than is used in conventional LCOS devices, where a thick LC layer can lead to a loss in efficiency and/or slow switching of the pixels. However, in the present invention, the switching speed of the pixels is not generally so important, and there is no significant detriment to the light loss caused by thick LC layers. The advantage provided by a thicker LC layer is that the device can be used to move larger particles, and that the device can have a greater throughput of particle flow.

Preferably the liquid crystal is a thermotropic liquid crystal .

Preferably the liquid crystal is a nematic liquid crystal. The invention is not necessarily limited to nematic liquid crystals, but these are the most widely used liquid crystals in LCOS devices and other display devices .

Preferably the device includes a cover member for defining a space for the layer of liquid crystal between the substrate and the cover member. Preferably the cover member further

includes at least one electrode opposing the array of electrodes of the substrate. This at least one electrode may ¬ be a common electrode. Preferably this at least one electrode is a transparent electrode. A typical known transparent electrode for TFT LCD and LCOS devices is an indium tin oxide (ITO) electrode.

In alternative devices, it is possible for the electrode array of the substrate to include laterally-opposed electrodes, so that the necessary electric field distribution is formed by placing adjacent electrodes at different potentials. Such an arrangement is particularly preferred when the liquid crystal layer is very thick, since it allows the formation of a high electric field strength independently of the thickness of the liquid crystal layer.

There are two specific particle movement mechanisms that have been identified by the inventors.

One particle movement mechanism relies on the formation of a line defect such as a disclination in the liquid crystal layer. Disclinations are usually disadvantageous in optical liquid crystal devices, since they can cause optical scattering and/or depolarisation of light. However, the present inventors have found that particles held in a liquid crystal layer are attracted towards disclinations, and vice

versa. Furthermore, disclinations can be formed by an appropriate control of the electric field distribution applied to the liquid crystal layer. Thus, it is preferred in the present invention to control the array of electrodes so as to form at least one disclination. One preferred mode for forming a disclination is to provide an electric field distribution having, in at least one dimension, a sharp change in electric field strength.

We note here that a disclination is not a phase boundary in the liquid crystal. Furthermore, we note that, in preferred embodiments of the invention, the disclination is controllably movable in the liquid crystal layer. This controlled movement is typically in at least one extension direction of the liquid crystal layer, i.e. in a direction orthogonal to a thickness direction of the liquid crystal layer. Furthermore, the controlled movement is preferably along a distance in said extension direction of at least two times (and preferably significantly more) the thickness of the liquid crystal layer.

In order to form a disclination by the effect of an electric field, it is desirable for the electric field strength to be high and/or for the rate of change of the electric field to be high. However, very fast continual electric field switching (of the order of MHz) will not be effective, since the liquid crystal will not be able to react fast enough to the changing

electric field (the result will be an averaging effect) . Preferably the electric field strength is at least 0.1 V per micron. More preferably the electric field strength is at least 0.2 V per micron, 0.5 V per micron or most preferably at least 1 V per micron. Typically the electric field strength is 100 V per micron or less, and more preferably is 75 V per micron or less, or 50 V per micron or less, or 25 V per micron or less, and most preferably is 10 V per micron or less.

The dynamics of the application of the electric field also has an effect on the formation of disclinations . It is preferred that the voltage is applied with a switch-on speed (or switch- off speed) in the kHz range, e.g. 1 kHz to 100 kHz is preferred (more preferably 1-10 kHz). This range is preferred because it is the range in which there is the most suitable trade-off between the relatively slow reaction speed of the liquid crystal molecules and the need for a high rate of electric field strength change in order to promote the formation of the disclination.

A particularly preferred electric field distribution, in one dimension, is a distribution having a gradual increase in electric field strength with distance terminated at a sharp decrease in electric field strength. It is possible to form a disclination using the opposite distribution.

In some embodiments, it is preferred to form a series of disclinations . In that case, a periodic electric field distribution is desirable. A particularly preferred waveform for this distribution is a sawtooth waveform. This may have a constant gradual gradient and/or a constant "flyback" gradient, but this is not essential (i.e. either gradient may have non-zero curvature) .

The use of a LCOS architecture is particularly preferred for the formation of disclinations, since LCOS devices have very small component dimensions (of the order of 90 run is readily achievable by CMOS foundries) . This means that it is possible to form electrodes having very small dimensions and spacings. In turn, this allows very fine control of the electric field distribution by suitable control of the potential of each electrode. In this way, it is possible to approximate a smooth sawtooth waveform for the electric field distribution. Such a waveform is suitable for blazed diffraction gratings, for example .

In the manner indicated above, it is possible to form a series of disclinations. It is furthermore possible to form a time- varying array of one or more disclinations by providing a suitable time-varying electric field distribution. Thus, preferably, the electric field distribution is spatially varied with time. Most preferably, the electric field

distribution is varied in a graduated manner in a series of frames, so that over said series of frames, the electric field distribution appears to move along the liquid crystal. In this way, the disclinations formed as a result of the electric field distribution similarly appear to move. It is possible that the disclinations themselves move between frames, or it is possible that the disclinations collapse and re-form in new positions. Provided that there is sufficiently small spatial movement of the electric field distribution between frames, the precise mechanism of disclination formation or movement is not important, and the present invention is not necessarily bound by any particular theory of disclination movement or continual formation-destruction-formation processes.

Thus, preferably, said one or more disclinations are caused to move or form in a time-varying manner so that they move (or at least appear to move) corresponding with the movement of the electric field distribution.

Particles in the liquid crystal typically cause local distortion of the director of the liquid crystal. This distortion is typically elastic. It is possible for an arrangement of a particle and a disclination to minimise free energy by becoming coincident. Thus, preferably said one or more disclinations become linked with said particle. Provided that the particle is sufficiently mobile, it is therefore

possible for the "movement" of the disclination caused by the movement of the electric field distribution to cause corresponding movement of the particle.

Where the disclinations are provided in a moving series, it is allowable for one particle to be moved along by more than one of the series of moving disclinations. This can be considered to be a particle being successively swept along by the series of disclinations. Thus, the average speed of the particle may be different from the average "speed" of the disclinations. This depends to some extent on the mass and size of the particle, but also on the degree of distortion to the director of the surrounding liquid crystal caused by the presence of the particle.

A second particle movement mechanism relies on the coupling of the director of the liquid crystal layer to flow. It is preferred in this mechanism to provide a liquid crystal layer which has a net flow when the director is aligned. For example, the liquid crystal molecules may be pre-tilted in order to provide such an arrangement .

In this mechanism, the electric field applied to a portion of the liquid crystal layer may be varied with time. A preferred embodiment uses a non-symmetrical time-varying electric field. For example, the electric field may be increased quickly

(causing rapid alignment of the director) and then allowed to decrease slowly (causing relatively slower de-alignment of the director) . For a particle entrained in the liquid crystal layer, the rapid alignment of the director tends to cause a relatively large movement of the particle, whereas the slow de-alignment causes only a small reverse movement of the particle. The result is a net movement of the particle over the cycle of varying electric field. Preferably, this operation is carried out a series of times, e.g. continually, so that the particle is moved in the required direction.

It possible to provide a device in which both the first and the second movement mechanisms operate.

Using an array of electrodes formed on the substrate of the device (such as are to be found in a typical LCOS device) it is possible to provide flow paths for the particles along the substrate. These flow paths can be defined by the applied electric field distribution alone. However, alternately, it is possible to pre-define at least one flow path by providing a conduit along the device, the conduit having said layer of liquid crystal. The conduit may be considered a track, since it will usually be essentially two dimensional for the purposes of moving the particle.

Most preferably, there are provided subsidiary transport paths connected at one or more branches with a main transport path. In this way, it is possible to conduct said particles along the main transport path and direct them, as necessary, along said subsidiary transport path. It is preferred that one or more of said analytical stations are situation along, or at one end of, said subsidiary transport path.

As will be apparent to the skilled person, the overall layout of the device may be similar to the layout of a microfluidic device such as a microfluidic lab-on-a-chip. However, the present device is preferably characterised by the provision of a particle transport path, the particle transport path being provided with said layer of liquid crystal. It is also preferably characterised by a very high density of electronic components (e.g. electrodes) built into the CMOS backplane.

Preferably, the device includes a port for introducing the particle into one or more transport paths of the device. The port may be in communication with a reservoir chamber on the device. Alternately, the port may be communicable with an insertion device, such as a micropipette device. The thickness dimension of the port is preferably less than 100 microns. Preferably the thickness is more than 10 microns, particularly where an insertion device is used to introduce the particle to the device.

Jang et al ("Anchoring of nematic liquid crystals on viruses with different envelope structures", Nano Letters, Vol. 6, No. 5, 2006, pp. 1053-1058) discuss the interaction of different virions with liquid crystal molecules, and in particular on the orientation effects on the liquid crystal molecules caused by the presence of such virions. Jang et al suggest that this effect can be used to amplify the presence of nanoscopic virions into micrometer-sized domains of liquid crystal that can be optically probed. The content of Jang et al is hereby incorporated in its entirety by reference. It is to be noted that Jang et al used a liquid crystal (4-cyano-4'~ pentylbiphenyl (5CB) ) that was non-toxic to the biological particles used in that study. Such a liquid crystal may also be used with the present invention.

The present inventors have realised that the effect shown by Jang et al may be usefully combined with the present invention in order to provide a further advantage. Thus, preferably the particle is located by its interaction with local liquid crystal molecules using the resulting effect on the director field of the liquid crystal surrounding the particle. As demonstrated by Jang et al, such an arrangement can be detected using optical techniques, such as optical microscopy. Preferably, in the present invention, there includes the step of identifying the particle based on its effect on the

director field of the surrounding liquid crystal. This may be achieved, for example, by polarised light microscopy.

The orientation of asymmetric particles can have an effect on the director field of the surrounding liquid crystal.

Accordingly, the orientation (or change in orientation) of such particles may be determined by a corresponding detection of the director field or change in the director field.

The use of the present invention to move nanoscale particles presents a challenge for determining the location of such particles within the device. It is possible that the device can include sensing areas for detecting the presence or passage of the particles (e.g. chemically, electrochemically, electrically or electromagnetically) , but a preferred mode involves determining the location of the particles based on the effect of the particles on the director field of the surrounding liquid crystal. For example, this may be via optical detection. Furthermore, it is possible to track the particles based on this method, since the shape of the director field can act like a "fingerprint" to locate (and optionally characterise) the particle.

In some embodiments, it is possible to carry out the optical detection of the particles using an optical device (e.g. a light microscope) that is not integral with the device. This

allows the analysis of light that passes through the liquid crystal layer in both directions (as a LCOS is intended to operate) so that the polarisation pattern of the liquid crystal layer can be analysed.

In some embodiments, it is possible (additionally or alternatively) to carry out the optical detection of the particles using an array of optical elements that are integral with the device. The use of a semiconductor backplane makes it particularly preferred to include an array of optical sensors in the device. Using typical CMOS architecture, it is possible to provide these at a very high density, to provide a correspondingly high resolution for the resultant optical detection. For example, optical sensors can be provided for each pixel, or for a selection of pixels (e.g. located at a particular region of the device) . In this way, the pattern of disruption of the director field of the liquid crystal surrounding the particles can be imaged. Furthermore, the movement of this pattern can also be detected, meaning that the pattern (and hence the particle causing the pattern) can be tracked.

It is therefore possible for the device (or an associated apparatus) to detect the position of the particle (and, in some embodiments, to identify or characterise the particle). This allows the tracking of a moving particle. Furthermore,

since the device can operate to controllably move the particle, it is possible for the device (or an associated apparatus) to move and guide the particle along a predetermined path. This can be achieved with positive verification due to the tracking of the particle.

Preferred and/or optional features of the present invention will now be further described by way of example with reference to the accompanying drawings, in which: Fig. 1 shows an greyscale optical photomicrograph of an exemplary embodiment of the present invention Fig. 2 shows a schematic line drawing version of Fig. 1.

As demonstrated in the following and as explained above, liquid crystals react dramatically with nano structures in the size range from below a micron to tens of nanometres. For example, liquid crystal director fields are aligned in contact with surface topography in this range. It is for this reason that the present invention allows the identification and/or indirect imaging and/or controllable movement of nano objects such as single carbon nanotubes or strands of DNA, when these objects are in contact with thermotropic liquid crystals.

Furthermore, the present invention demonstrates the formation of defects on a nano scale in liquid crystals. For example

the formation of an S=l/2 disclination is demonstrated by the application of a lateral electric field.

Nanoscale biological entities such as proteins, cells, strands of DNA or virions are capable of being immersed in nematic liquid crystals, The director field adopted around them can imaged and identified by polarised light microscopy. This is one instance of the susceptibility of liquid crystals to the shape and surface structure of nano particles. Although the present invention has particular utility in dealing with biological entities, it also has utility for a wide range of non-biological entities such as organic, inorganic, metallic and composite nanoscale particles.

Such particles can be manipulated (e.g. moved translationally or rotationally) in a liquid crystal media over a silicon (or other semiconductor) backplane by suitable control of an array of electrodes associated with the backplane. The reason for choosing a silicon backplane is the ready availability of very high resolution processing techniques for the formation of CMOS devices as discussed above, e.g. in LCOS devices.

Fig. 1 shows a shows a greyscale optical photomicrograph of an exemplary embodiment of the present invention. Fig. 2 shows a schematic of the photomicrograph of Fig. 1, in which certain features are omitted for the sake of clarity, and others are

stylized, also for the sake of clarity. Both will be described together.

In the photomicrograph, part of an adapted LCOS device is shown. In the device, there is a substrate having an array of electrodes as in a conventional LCOS device, the electrodes being associated with corresponding pixels. The pixels themselves are very small and are only just individually visible. This shows an important scale difference between LCOS devices and conventional TFT LCDs.

In the photomicrograph, the scale is such that 1 mm on the paper image is equivalent to about 10 microns (i.e. a magnification of about 100 times). The image is taken using a light micrograph under crossed polarisers and the light is reflected from the device.

A reflective metallic film is disposed above the electrode array (but not in electrical contact with the electrodes) . A layer of liquid crystal of about 5 microns is disposed between the reflective metallic film and a polarising cover member having a transparent electrode (e.g. ITO) formed opposing the electrode array on the substrate. In other devices, a liquid crystal layer of thickness 20 microns is used.

In operation, the device can be controlled so that the pixels are switched between an off-state and an on-state (and to degrees in between these states) so that the pixel is either bright or dark when light is incident on the device (or to a greyscale brightness) , respectively. This is achieved as in a typical LCOS device.

In the photomicrograph, the region 10 is in the off-state, and so is dark. Region 12 is in the on-state, and so is bright.

It will be noted that there are particles 14 in the image. (In Fig. 2, all of the particles 14 are indicated as being of the same size and shape, which of course is a simplification.) These are dirt and dust particles that have been deliberately introduced under the polarising cover member, to be surrounded by liquid crystal. Following this, the electrode array of the region 12 has been operated to produce disclinations . A portion of one disclination is shown at 16 and another is shown at 18.

These disclinations are formed by driving a sawtooth waveform of electrical field distribution across the pixels of the active region 12. The waveform is provided so as to ensure an electric field strength of 1-10 volts per micron across the liquid crystal layer at the locations at which disclinations are required. In normal circumstances, such disclinations

form and then are destroyed. However, it is possible to provide a moving series of such disclinations by progressively moving the electric field distribution across the active region by applying suitable "frames" of signals to the pixels of the active region, each frame corresponding to an incremental progression of the previous frame.

The interaction between disclinations and particles is shown in the photomicrograph. Reference numeral 20 indicates a portion of the disclination that has a zig-zag shape. The reason for this shape (rather than a smooth curve) is considered to be a series of interactions between the elastic director field distortions surrounding three particles and the director field discontinuity defined by the disclination. For reasons of reduction of free energy, the disclination is coincident with the particles. It is possible to see similar interactions between disclination 18 and other particles elsewhere in the active region 12.

Thus, disclination 18 and the particles shown along its length exert a force on each other. Consequently, movement of disclinations (or incremental progression of formed disclinations) tends to move suitable particles. Thus, the moving series of disclinations described above provides a mechanism for controllably moving such particles, since the

movement of the disclinations can be controlled by suitable control of the electrode array.

It is not only possible to translationally move particles, but suitable control of the signal applied to the electrodes in the array also allow the rotation of asymmetrical particles (asymmetric in shape or polarisability) such as carbon nanotubes . This is particularly the case where the particle tends to align preferentially with (or at some predetermined angle with) the director field of the liquid crystal.

Operation of the device to rotate the director field at the relevant part of the device (i.e. at the pixel or pixels at which the particle is located) allows the particle to be reoriented along with the liquid crystal molecules.

Furthermore, it is possible to harness a different mechanism in order to translationally move the particle. Since the director couples with flow, it is possible to ensure that a majority of the liquid crystals rotate in a preferred direction in order to re-align the director. One way to do this is to pre-tilt the liquid crystals in a known manner. In that case, the application of the necessary electric field to align the director causes flow of the liquid crystal. Removal of the electric field reverses the flow, but typically asymmetrically (i.e. more gradually than the initial flow).

For a particle surrounded by the liquid crystal, the particle reacts differently to this flow, depending on the flow speed. Thus, for rapid switch-on of the electric field, the flow rate is high. For gradual switch-off of the electric field, the flow rate is relatively slow and in the opposite direction. The result is net flow of the particle, since it will typically move further due to the high flow rate than due to the low reverse flow rate. Repeated application of suitable electric field distributions along the device therefore cause particle movement.

The particle is moved along predetermined transport paths. These are conduits of the layer of liquid crystal. In some devices, there is a main transport path (a highway) along which are subsidiary branches leading off. The subsidiary branches operate in a similar manner to the main transport path. The subsidiary branches lead to analytical stations at which further electronic components are built into the CMOS backplane. For example, an analogue-to digital converter can be built in to an analytical station, for the purpose of carrying out cyclic voltammetry to an analyte particle. CMOS gates can be used to identify biological entities, for example, by detecting electrochemical processes, as discussed above (see P. Migliorato et al) . In order to study biological material in this way, it is of course preferred to use liquid crystal that does not detrimentally affect the biological

material. The materials used by Jang et al (see above) are suitable for this purpose.

One or more of the analytical stations has an optical detecting element built into the CMOS backplane. Such detecting elements are known and can have a size smaller than the extent of each pixel in a LCOS array. One specific use of such an optical detecting element, or more especially of an array of optical detecting elements, is at an analytical station, the element or elements being configured to detect fluorescence as a result of a fluorescent tag attached, e.g., to a biological entity.

Jang et al have demonstrated that it is possible to differentiate several different types of virion by observing the pattern of the director field in the liquid crystal surrounding the virion by polarised light microscopy. Embodiments of the present invention extend this, and provide the tracking of moving particles by tracking the pattern of the corresponding moving director field. Furthermore, this can be achieved whilst the particle is being moved by operation of the device as described above. In this way, it is possible to controllably move and track the particles along the transport path through the device. In one embodiment, this tracking is via polarised light microscopy. In another embodiment, this is via a suitable array of optical detector

elements in the device. The very small pixel size achievable with CMOS technology (see Figs. 1 and 2) allows a high density of optical detector elements and therefore a high reliability of detecting and tracking the characteristic pattern of the director field associated with each particle.

In one particular embodiment, a population of buckyballs (Ceo or higher) is inserted into the transport path using a needle pipette. This is a useful indicator of the abilities of the device, since each particle is substantially identical (for a pure population of buckyballs) . The particles provide an extended pattern to the observed director field surrounding the particles, allowing the particles to be tracked as well as controllably moved as described above.

Preferred embodiments of the invention have been described. Modifications of these embodiments, further embodiments and modifications thereof will be apparent to the skilled person on reading this disclosure and as such are within the scope of the present invention.