GB2332511A - Liquid crystal sensors for sensing analyte molecules - Google Patents

Liquid crystal sensors for sensing analyte molecules Download PDF

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GB2332511A
GB2332511A GB9726923A GB9726923A GB2332511A GB 2332511 A GB2332511 A GB 2332511A GB 9726923 A GB9726923 A GB 9726923A GB 9726923 A GB9726923 A GB 9726923A GB 2332511 A GB2332511 A GB 2332511A
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membrane
liquid crystal
light
molecules
analyte
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Paul Nicholas
Tony Mccollum
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Priority to GB9726923A priority Critical patent/GB2332511A/en
Publication of GB9726923D0 publication Critical patent/GB9726923D0/en
Priority to AU17703/99A priority patent/AU1770399A/en
Priority to EP98962568A priority patent/EP1047930A1/en
Priority to CA002314366A priority patent/CA2314366A1/en
Priority to PCT/GB1998/003841 priority patent/WO1999032878A1/en
Publication of GB2332511A publication Critical patent/GB2332511A/en
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/59Transmissivity
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/7769Measurement method of reaction-produced change in sensor
    • G01N2021/7783Transmission, loss

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  • General Health & Medical Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

A device for sensing one or more analyte molecules comprises a membrane (1) whose surfaces are rendered electrically conducting; a liquid crystal material or liquid crystal blend impregnated within the membrane; a light source; a light sensor; and light guides (8) between the light source and one surface of the membrane (1) and between the other surface and the light sensor, whereby the light sensor senses light transmitted through the membrane (1) from the source via the light guides (8). The light transmitted through the liquid crystal is affected by the presence of particular molecules in a liquid or gas passed through holes (7) into a space adjacent the membrane. Different sinusoidally modulated voltages applied across the two surfaces of the membrane change the response of the liquid crystal and render the device sensitive to different molecules. Further optical fibres (9) form a reference channel where the liquid crystal is not exposed to the analyte.

Description

1 LIQUID CRYSTAL SENSORS is 2332511 The present invention relates to a
device for sensing and identifying one or more analyte molecules using optical properties of liquid crystals. It is known 'that liquid crystal membranes can have a high degree of specificity towards molecules permeating through them. This selective behaviour or permselectivity can be controlled so as to enhance the transmission of species of interest. Such systems exploit the spontaneous or induced molecular ordering exhibited by liquid crystal molecules which encourages anisotropic molecular interactions. Differences in the steric (size and shape) and dipole-dipole (solubility) interactions between different permeants and the liquid crystal are thus enhanced, altering membrane selectivity. The present invention further exploits these interactions to detect the presence of permeant species by monitoring the dynamic optical properties of liquid crystals.
Liquid Crystal, LC, sensors are known which rely on measuring a colour or refractive index change to detect the species of interest. Such systems can be based around optical fibres to convey light to and from a detecting region at the end of the fibre. They tend to be specific to one compound and so arrays of different sensors are required to sense more than one species.
EP 0441120 (Yeda Research and Development Co. Ltd.) is directed towards a biosensor for qualitative and quantitative analysis comprising (1) a reference electrode at its upper part, (2) a recording electrode at its bottom, and (3) an amphiphilic liquid crystalline membrane composed of a lipid bilayer doped with synthetic or biological ion channels. The sensor works by the opening of ion channels activated by the interaction of the ion channel or ion channel site with a chemical entity. This results in an increased conductance which, if calibrated appropriately, can be related to the concentration of the desired species. However, the system has 2 to be respectively calibrated for each separate antibody.
Devices are known which comprise thin, ceramic membranes which may or may not be surface treated and are impregnated with electroactive liquid crystals. However, these membranes have been used to measure electrical and optical (not dynamic optical) parameters and the dielectric characteristics of the liquid crystal. Various studies have been undertaken to measure dielectric properties and liquid crystal NMR spectra which measure relatively rapid (MHz range) liquid crystal molecular motions directly. This type of configuration has not been used as a chemical sensor.
It is an object of the present invention to provide a device which is capable of sensing the presence of and identifying a plurality of molecular species without the need to resort to an array of sensors, each specific to one analyte, or having to recalibrate or in any way modify the system.
The invention consists of a device for sensing one or more analyte molecules, comprising: a membrane whose two surfaces are rendered electrically conducting; a liquid crystal material or a liquid crystal blend impregnated within the membrane; a light source; a light sensor; a light guide between the light source and a first surface of the membrane; and a light guide between the second surface of the membrane and the light sensor, whereby the light sensor senses light from the light source which has been transmitted through the membrane via the light guides. Any one or more analyte molecule causes a distinctive and detectable change in the transmitted optical beam.
Thus, one advantage of the present system is that a number cf, molecules can be sensed simultaneously by the same sensor without separate calibration and measurement being necessary, whereas, the sensors of the prior art are specific to one species and therefore for complete identification of a mixture of compounds, an array of sensors is necessary. This would be both expensive and time consuming.
The use of the optical properties of the liquid crystal i 1 i 1 3 is in response to an applied field allows a number of different molecules to be identified in one sensor. The optical response may be converted into an electrical signal which is split into 3 channels. The combination of high and low frequency response is characteristic of the analyte molecule being sensed and the DC offset is dependent upon concentration. For more than one analyte, the DC offset is a composite response, i.e. it is a signal representative of a combined concentration.
In a preferred embodiment, the membrane is constructed of a material containing uniform channels connecting both surfaces. Preferably the membrane is constructed of a ceramic material; each surface is sputter coated with a thin layer of conducting material to render it electrically conducting; and the surface of the membrane is treated with a solution of alkyl acid prior to the addition of the liquid crystal.
Preferably the conducting material is gold, another metal or a conducting polymer such as polypyrrole.
Preferably, the liquid crystal in this embodiment is K15 or CB5, supplied by Merck UK Ltd. The interaction between the liquid crystal and the alkyl acid on the surface of the membrane causes the liquid crystal molecules to lie parallel to the surface of the membrane (across the channels of the membrane) resulting in low optical transmission. When a voltage is applied, the membrane becomes more transparent therefore a periodic waveform about 0 V will produce a corresponding transmission signal of varying intensity.
In a seconj embodiment, the membrane is constructed of a ceramic material or material containing uniform channels connecting both surfaces; each surface is sputter coated with a thin layer of conducting material to render it electrically conducting; and the membrane is impregnated with a blend of liquid crystals. Again, the conducting material is preferably gold, another metal or a conducting polymer such as polypyrrole.
Preferably, in this embodiment, the blend of liquid crystals is a combination of K15 and 8 6 by weight of CE5.
4 is The liquid crystal molecules in the blend naturally adopt an helical orientation induced by the presence of chiral CES molecules. Therefore the molecular long axes are tilted with respect to the channel long axis and again the result is low optical transmission. As before, a periodic waveform about 0 V will produce a similar transmission signal of varying intensity as in the first embodiment.
The invention also extends to a process for the sensing of one or more molecules comprising the application of a periodic waveform about 0 V across a device as described above; and simultaneous interrogation of the optical transmission of the device containing the analyte, the transmission output signal being converted into an electrical signal.
Preferably the electrical signal is split into three channels. The first channel being the composite optical response. The second channel is a low frequency response with a cut-off frequency of at most 200 Hz, more preferably 150 Hz and most preferably 100 Hz. The third channel is a high frequency response with a cut-off frequency of at least 800 Hz, more preferably 900 Hz and most preferably 1 kHz. As explained above, the low and high frequency responses taken together are characteristic of the solvent molecule being sensed and the DC offset response is dependent upon concentration.
The invention further extends to a process for the sensing of one or more molecules on the channel surface of the membrane. Preferably, the sensing comprises observation of the dynamics of the liquid crystal. This identification of molecules on the channel surface of the membrane is in addition to the detection and identification of molecules which have dissolved in the liquid crystal.
While a few of the applications of the liquid crystal sensing device have been described above and will be explained in more detail below, the use of it is not limited to these applications. Further use and development of the sensor may be made in the following areas: altering surface is treatment to enhance sensitivity for specific analyte molecules e.g. chiral specific analysis; liquid crystals bonded directly to the surface; liquid crystal blends; blends of liquid crystals and non-liquid crystal materials; the use of polarised light to enhance the system sensitivity to specific interactions; the use of fluoresc-ent surface coatings and/or liquid crystals to yield information concerning the chemical interaction between molecules; using reflected light to investigate surface interactions; using interferometric and holographic measurements to measure bulk and surface liquid crystal dynamics; the deposition of liquid crystal monolayers on channel surfaces to enhance detection sensitivity; dielectric measurements in addition to or instead of optical interrogation; two dimensional mapping of the sample to yield kinetic data assisting identification of the analyte molecules; the use of membrane stacks to separate molecules as they migrate down the stack as well as detecting their presence in each membrane element; alternative methods of molecular alignment e.g. magnetic field, temperature change, mechanical forces as well as the applied voltage described in detail in this document.
The data obtained from the sensors may be interpreted by signal processing. The periodic waveforms generated by the sensor represent several constituents in the analyte mixture, interactions between the constituents, effects due to the instrumentation such as random noise, and changing environmental conditions that affect the signal baseline. However, in combination with this complex of data, there will be a number of independent variations present in the signal, the largest of which represent the analyte mix. To extract meaningful information from the sensor waveforms, they are preprocessed and subjected to statistical analysis as described below.
The preprocessing procedure is used to reduce random variations in the signal and may consist of one or more of the following:
1. low pass filtering or autocorrelation - noise ir. the 6 original signal can be reduced either by low pass filtering or autocorrelation. Low pass filtering smooths the data using local averaging over time. Autocorrelation reduces noise by summing subsequent instances over the entire period of the waveform. Because the signal is repetitive, the underlying signal is enhanced, while random noise tends to- cancel out. 2. DC offset correction or extraction of first derivative the repetitive waveform is superimposed on a low frequency or DC component. This can be extracted out by subtraction of a constant value, or by high pass filtering. The first derivative of the signal represents the slope at every point of the waveform, and is unaffected by low frequency or constant components.
3. Scale normalisation or variance scaling - as the concentration of the analyte changes, the peak-to-peak range of the waveforms vary. To compensate for this, the dynamic range of the signal can be normalised to a constant interval. Variance scaling is calculated by dividing the signal at each point by the standard deviation of the overall data.
4. Mean centring - for subsequent statistical analysis it is useful to subtract the mean value from the signal.
The characteristics of the signal can be extracted by a range of statistical and analytical methods including use of: mean, median and mode values; moments; variance; number of peaks; normal, F and T distribution; chi square distribution; auto power density spectrum; cross- power density spectrum; autocorrelation; fourier analysis; and principal compoient decomposition.
The data generated by this analysis are classified by examining their distribution and labelling them as due to an appropriate analyte. The method involves an off -line training phase where the system is exposed to a number of samples. During actual use, the incoming data is compared to the training set. There are several appropriate pattern classification, or cluster analysis methods, including adap t ive vector quantisation, K-means clustering and principle value decomposition. The last of these will be j 1 7 is explained in more detail here to explain how the information that corresponds to the analyte is extracted.
The waveforms generated by the sensor are digitised and represented by a vector of elements x. The mean value of this vector is x. The data is then transformed as follows:
(y-y) = A(x-x) where the rows of A are the eigenvectors of Cx such that Cx = (l/n) (X_X) (X_X) T Cx is the covariance matrix of the variables x, centralised about their means.
An important property of the transformation is that the terms (y-y) have associated eigenvalues that are also the value of their variance in the transformed domain. The linear combination with the highest eigenvalue is therefore the linear combination with the highest variance. The principal component has the largest possible variance of any possible linear function. The second component has the largest variance under the condition that it is uncorrelated with the first. The third component will have the smallest variance subject to the constraint that it is uncorrelated with the others.
Because the terms (y-y) are uncorrelated, they can be separated. The transformed waveform can be built up as a linear combination of the components.
The principal components can be used for classification of the analyte. The process starts with training phase, carried out off-line as a onetime procedure. A set of waveforms corresponding to known analytes is generated, and a matrix A is produced for this set. Each row of A (the eigenvectors) can be considered as a breakdown of the variation in the waveforms. The eigenvectors with the lowest eigenvalues contribute least, and tend to represent random effects such as noise, and can be discarded. only the rows (the eigenvectors) of A that correspond to the principal components need to be retained, reducing the computational demands. The resultant A matrix represents the space of the training set. For each known analyte, its distribution in 8 is this space is calculated, by projecting the waveform on to the matrix, and a weighting value is computed that represents this distribution.
For analyte classification, the data is projected onto the A matrix and a weighting value is calculated. The new weight is compared to the set of weights generated during the training stage. If the difference between the weights is less than a tolerance value, the analyte is classified according to the minimum of the differences.
if any of the elements in the training set corresponds to the unknown analyte waveform, a close match will be found. If the analyte is contaminated, for example, the fit may be out of range to qualify as an acceptable match, but the method will still be able to classify the signal according to the training sample it is closest to.
Although a specific excitation/ interrogat ion regime is described, there are many possible ways to enhance the data being recorded. These include: multifrequency modulation a modulation signal consisting of a combination of several sinuscids of different frequencies; and frequency sweep modulation - a modulation signal consisting of a linearly increasing modulation frequency. The application of voltage pulses may also be advantageous.
In specific cases the applied frequency may have a direct influence on the bulk orientation of the liquid crystals. Some electroactive liquid crystals undergo a change in the sign of their dielectric anisotropy when subjected to electric fields exceeding a certain threshold frequency. This is observed as a change in the orientation of the molecular long axis from parallel to the electric field to perpendicular to it or visa versa. This is known as two frequency switching and is sometimes exploited to reorientate liquid crystal molecules in display devices. The judicious selection of liquid crystals or liquid crystal blends could exploit this phenomenon for sensor and separation processes. Different liquid crystal components in a blend could be switched independently so highlighting specific analyte
9 interactions.
The data handling may also be extended to permit multichannel, multifrequency analysis rather than just low and high frequency channels used currently. Data process ing/analysi s will almost certainly involve techniques such as Fast Fourier Transform (FFT) to measure f-requency and power response spectra.
To date, interrogation of the sensor has been accomplished -using relatively simple optical techniques.
Apart from making direct electrical measurements of dielectric properties there is also the possibility that techniques such as nuclear magnetic resonance (NMR), electron spin resonance (ESR) and infrared, UV, visible and raman spectroscopy could also be used to monitor liquid crystal dynamics.
The membrane itself could also take many forms. To date, the only matrix used to contain the liquid crystal has been an Anopore ceramic membrane made from alumina (alumin-Jum oxide). Other materials with different microstructures may also be suitable. For example, the manufacture of polydisperse liquid crystal (PDLC) films could provide an alternative means by which small droplets of liquid crystal could be suspended in a matrix; in this case a polymeric matrix.
Thin layers of silica (silicon dioxide), other oxides, nitrides or carbides impregnated with liquid crystal may also perform the same function. The microstructure of these layers can be finely coLrolled for optimum results and are readily formed on silicon wafers.
A well defined layer or layers of liquid crystal on a suitable substrate could also be manipulated by electric/magnetic fields and operate as a sensor.
The invention may be put into practice in various ways and two specific embodiments will be described by way of example to illustrate the invention with reference to the accompanying drawings, in which:
Figure 1 is a schematic block diagram of the excitation and interrogation regime used for the membrane sensors; Figure 2 is the chemical structure of the liquid crystal identified as K15 or CB5 as supplied by Merck UK Ltd.; Figure 3 is the chemical structure of the liquid crystal identified as CE5 as supplied by Merck UK Ltd.; Figure 4 is an enlarged, expanded cross-section of the membrane holder; Figure 5 is a typical excitation waveform applied to the membrane sensor; Figure 6 is an response raw signal Figure 7 is an response raw signal Figure 8 is an response raw signal SAl benzene in air; example of the high and low frequency output for 10gl toluene in air; example of the high and low frequency output for 10gl benzene in air; example of the high and low frequency output for a mixture of Sgl toluene and Figure 9 shows the raw optical response and the applied low frequency (about been surface treated Figure 10 shows low frequency (about been surface treated Figure 11 shows low frequency (about been surface treated Figure 12 shows low frequency (about 2 Hz) sine wave for a membrane which has with acetic acid; the raw optical response and the applied 2 Hz) sine wave for a membrane which has with hexanoic acid; the raw optical response and the applied 2 Hz) sine wave for a membrane which has with decanoic acid; the raw optical response and the applied 2 Hz) sine wave for a membrane which has been surface treated with octadecanoic (stearic) acid; Figure 13 is a Fourier Transform of the raw response of figure 9; Figure 14 is a Fourier Transform of the raw response of figure 10; Figure 15 is a Fourier Transform of the raw response of figure 11; and, Figure 16 is a Fourier Transform of the raw response of figure 12.
The system, as indicated in figure 1, consists of an is Anopore ceramic membrane 1 which is illuminated on one side by a stabilised light source. The membrane has a liquid crystal impregnated within it and on the application of a periodic waveform about 0 V a transmission signal of varying intensity is measured. The transmitted light is detected by a photodiode 2 and converted into an electrical 'signal which is amplified and split into 3 channels A, B and C. The identity of the analyte molecules can be determined from the change in transmission signal after the analyte is added.
The actual sensor comprises an Anopore (Trade Mark) ceramic membrane 1, for example sold by Whatman UK. In this example the membrane 1 is approximately 26 mm in diameter and 60 microns thick. The membrane 1 has a sieve like structure with well defined channels perpendicular to and connecting its two faces. The channel diameters are 0.2 microns in this specific example although other Anopore membranes are available with 0.1 and 0.02 micron channel diameters.
The two faces of the membrane 1 are rendered conducting by sputter coating a layer of gold (or any other conducting material, e.g. a metal, polypyrrole) onto the surfaces. This is followed by a chemical treatment to modify the surface of the channels and involves immersion of the sputter coated membrane 1 in a solution of an alkyl acid such as hexanoic, decanoic or stearic (octodecanoic) acid. The preferred alkyl acid is stearic acid because the long hydrocarbon chain length decouples the liquid crystals from the surface most effectively. The acid group, which is at one end of the hydrocarbon chain, becomes anchored to the channel surface and the chain extends perpendicularly from the surface into the channel volume. Excess solvent is removed by pressing the membrane 1 between two pieces of filter paper and any residual solvent is removed in a vacuum oven.
The membrane 1 is prepared by placing it on a piece of filter paper on a hot plate. The entire exposed membrane surface is then covered with a thin film of a nematic electroactive liquid crystal and left for a time (typically of the order of 24 hours). This ensures complete impregnation 12 of the membrane 1.
The temperature of the hot plate is such that the liquid crystal is in its isotropic liquid phase which ensures minimum viscosity. For example, K15 (or C25) is in its nematic liquid crystal phase between 25 and 350C. Beyond 350C it is an isotropic liquid and below 250C it is a' crystalline solid. CE5 is a crystalline solid below 18.70C, exists in a chiral smectic-A phase between 18.7 and 420C and is an isotropic liquid beyond 47.50C.
The liquid crystal used in this case is identified as K15, which exhibits a nematic phase between 25 and 350C as explained above, and is supplied by Merck UK Ltd. The full chemical structure is shown in figure 2. The chemical name for K15 or CE5 is 4-cyano-41-pentyl biphenyl.
An alternative system can also be employed whereby the ceramic membrane 1 is sputter coated with a conducting material as before but it is not subjected to any surface treatment prior to impregnation. The liquid crystal used is a blend of K15 and 85 by weight of an optically active, chiral nematic (or cholesteric) liquid crystal identified as CE5 and supplied by Merck UK Ltd. The full chemical structure of CE5 is shown in figure 3. The chiral centre of the liquid crystal is indicated by the asterisk.
The use of the device as a sensor involves the application of voltages across the membrane 1 using the sputter deposited electrodes, and simultaneous interrogation of its optical transmission. A membrane holder 3 was devised in which the membrane 1 could be clamped, electrically connected and optically interrogated using optical fibres.
One of the faces of the membrane 1 is exposed to the analyte permitting its diffusion into the system as shown in figure 4. This configuration prevents any current leakage when used in aqueous media.
Figure 4 shows an enlarged, expanded cross-section of the membrane holder 3. The holder 3 consists of two components, one each on either side of the membrane 1. One component 4 is electrically insulating and the other is j: 1 1 13 component 5 is made of metal to form an electrical contact with one side of the membrane 1. The electrical contact on the other side is made through an insulated electrical contact 6. As stated above, the Anopore porous ceramic membrane 1 is sputter coated with a metal e.g. gold on both sides.
The metal component 5 has holes 7 to allow the sample analyte liquid or gas access to one side of the coated membrane 1. Two sets of optical fibres 8, 9 are aligned on either side of the surfaces of the coated membrane 1. One pair of optical fibres 8 are aligned to pass through the sample cavity and they are referred to as the Ilsamplell optical fibres. The second pair of optical fibres 9 are Ilreferencell optical fibres used to detect small differences is between the exposed "sample" area of the membrane and the unexposed regions.
one of each pair of optical fibres is connected to light emitting diodes, LEDs, to direct infrared and red light to the membrane. The light transmitted through the membrane is captured by the second optical fibre of each pair on the opposite side of the holder. The transmitted light is detected by a photodiode connected to an oscilloscope and computer data capture interface. This configuration of optical fibres minimises stray light interference and ensures a fixed geometry, thus optimising the signal to noise ratio of the captured data.
The two components 4, 5 are joined together around the coated membrane 1 by means of fixing screws 10 threaded into fixing holes 11. The membrane is sealed within the holder with the aid of a peripheral sealing ring 12. The membrane holder 3 is then placed in the system as shown in figure 1.
Prior to the application of a voltage across the surface treated K15 membrane, the liquid crystal molecules lie parallel to the membrane surfaces (across the channels) and optical transmission is relatively low. A sufficiently high electric field will reorientate the liquid crystal molecules perpendicular to the membrane surfaces increasing light 14 is transmission. Thus a periodic zero crossing waveform will induce a corresponding periodic optical transmission signal of varying intensity.
The liquid crystal molecules in the untreated K15/CES impregnated membrane of the second embodiment naturally adopt an helical orientation induced by the presence of chiral CES molecules. Thus, the molecular long axes are tilted with respect to the channel long axis and the application of a sufficiently high electric field reorients the liquid crystals so that they lie parallel with the channel axis. A periodic zero crossing waveform will induce a corresponding optical response similar to that seen for the treated K15 membrane.
The electrical stimulus applied across the membrane 1 is an amplitude modulated signal of approximately 400 V p-p (peak to peak), symmetrical about 0 V as shown in figure 5 The modulation is sinusoidal with a frequency in the range 1 kHz to 15 kHz. An unusual feature of the carrier signal is that it is much lower in frequency than the modulation, and is a triangle waveform in the range 0.5 Hz to 10 Hz. A modulation level of approximately 250-b was used experimentally.
The optical fibres are used to couple the input and output light to and from the membrane. The optical interrogation beam is supplied by an 800 nm LED driven from a stabilised power source. A photodiode 2 is used to sense the transmitted. output, converting it into an electrical signal that is fed to a balanced preamplifier as shown in figure 1. The output of the preamplifier is split into three channels A, B, and C. The f irst channel A is the composite optical response, consisting of an overall DC offset upon which the response to the modulation signal is imposed. The second channel B is fed to an electrical low pass filter with cut-off frequency of 100 Hz, the output of which indicates the response of the membrane to the low-frequency triangle carrier signal. The third channel C is fed to a high pass filter with cut-off frequency of 1 kHz, the output of which is is indicates the response of the membrane to the modulation frequency. The signal is then demodulated with a precision RMS detector. In uncontaminated air, the overall DC offset is constant for a given
temperature. The low-pass signal shows a complex but periodic form at the same frequency as th( modulation carrier. The detected high pass signal gives two peaks, corresponding to the rising and falling gradients of the triangular carrier.
With the introduction of the analyte, the "sample" DC offset will change, indicating an increase in light transmission through the membrane. The complex form of the low pass signal also changes, as do the number of peaks detected from the high pass signal. The precise nature of the changes in the observed waveforms are specific to the analyte concerned and its concentration.
As stated above, the "reference" optical fibre can be used to detect small differences between the exposed "sample" area of the membrane and the unexposed regions. However, over time, analyte may diffuse into the reference region and the holder will have to be reset.
An example of the high and low frequency response raw signal output for 10A1 toluene in air is shown in figure 6. This was carried out at 380C and using a mixture of K15 and 0.2gm decanoic acid. The low frequency response is indicated by Li and the high frequency response by Hi.
A further example of the high and low frequency response raw signal outpJ for logl benzene in air is shown in figure 7. Again, this was carried out at 380C and using a mixture of K15 and 0.2gm decanoic acid. The low frequency response is indicated by L2 and the high frequency response by H2.
As stated in the object of this invention, it is possible to detect more than one analyte species at one time and an example of this multiple detection is included in figure 8. This shows the high and low frequency response raw signal output for a mixture of SA1 toluene and 5il benzene. The conditions are as for the previous 2 examples. The low 16 is frequency response response by H3. distinguish using advanced devices; normally required.
As mentioned above, it is a further a#)ect of the present invention that the dynamics of the liquid crystal can be exploited to identify molecules on the channel surface of the membranes. This is in addition to detecting and identifying molecules which are dissolved in the liquid crystal. Figures 9 to 12 show the raw optical response for a variety of surface treated membranes.
The membranes were surface treated with alkyl acids having different chain lengths - acetic acid (2 carbons), hexanoic acid (6 carbons), decanoic acid (10 carbons) and octadecanoic or stearic acid (18 carbons) for the membranes in figures 9 to 12 respectively. The liquid crystal employed is K15 and the electrical stimulus applied is a low frequency sine wave which is not modulated.
Figures 13 to 16 show the Fourier Transforms of the raw responses of figures 9 to 12 respectively. It is clear from both the raw response and the corresponding Fourier Transform that the behaviour of the liquid crystal under the influence of the applied voltage is highly sensitive to the surface layer. This sensitivity can be used to detect and identify molecules on the surface of the membrane, in addition to the molecules dissolved in the liquid crystal.
I is indicated by L3 and the high frequency These 2 compounds are difficult to simple discrete sensors or even on more preseparation of these compounds is 17

Claims (1)

  1. CLAIMS is A device for sensing one or more analyte molecules, comprising:
    a membrane whose two surfaces are rendered electrically conducting; a liquid crystal material or a liquid crystal blend impregnated within the membrane; a light source; a light sensor; a light guide between the light source and a first surface of the membrane; and a light guide between the second surface of the membrane and the light sensor, whereby the light sensor senses light from the light source which has been transmitted through the membrane via the light guides.
    A device as claimed in Claim 1, in which the membrane in constructed of a material containing uniform channels connecting both surfaces.
    3.
    A device as claimed in Claim 1 or Claim 2, in which the membrane is constructed of a ceramic material.
    A device as claimed in any preceding Claim, in which each surface is sputter coated with a layer of conducting material to render it electrically conducting.
    A device as claimed in Claim 4, in which the conducting material is ' gold, another metal or a conducting polymer such as polypyrrole.
    6. A device as claimed in any preceding Claim, in which the surface of the membrane is treated with a solution of alkyl acid prior to the addition of the liquid crystal.
    7. A device as claimed in any preceding Claim, in which the liquid crystal is K15 or CB5.
    8. A device as claimed in any of Claims 1 to 5, in which 18 the membrane is impregnated with a blend of liquid crystals.
    A device as claimed in Claim 8, in which the blend of liquid crystals is a combination of K15 and 8 '-. by weight CE5.
    10. A device as claimed in any preceding Claim, in which the light sensor is a photodiode.
    11. A device as claimed in any preceding Claim, including a plurality of light sources and/or a plurality of light sensors.
    is 12. A process for the sensing of one or more molecules which comprises applying a periodic waveform across a device as claimed in any preceding claim, simultaneously interrogating the optical transmission of the device containing the analyte, and converting the transmitted output into an electrical signal.
    13. A process as claimed in Claim 12, in which the electrical signal is split into three channels.
    14. A process as claimed in Claim 13, in which one channel records the low frequency response with a cut-off frequency of at most 200 Hz, preferably 150 Hz and most 7 preferably 100 Hz.
    is.
    A process as claimed in Claim 13 or Claim 14, in which one channel records the high frequency response with a cut-off frequency of at least 800 Hz, preferably 900 Hz and most preferably 1 kHz.
    16. A process for the sensing of one or more molecules on the channel surface of the membrane.
    19 17. A process as claimed in Claim 16 in which the sensing comprises observation of the dynamics of the liquid crystal.
    18. A device and process for sensing one or more analyte molecules constructed and arranged substantially as herein specifically described with respect to and as shown in figures 1 and 3 of the accompanying drawings.
GB9726923A 1997-12-19 1997-12-19 Liquid crystal sensors for sensing analyte molecules Withdrawn GB2332511A (en)

Priority Applications (5)

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GB9726923A GB2332511A (en) 1997-12-19 1997-12-19 Liquid crystal sensors for sensing analyte molecules
AU17703/99A AU1770399A (en) 1997-12-19 1998-12-18 Liquid crystal sensors
EP98962568A EP1047930A1 (en) 1997-12-19 1998-12-18 Liquid crystal sensors
CA002314366A CA2314366A1 (en) 1997-12-19 1998-12-18 Liquid crystal sensors
PCT/GB1998/003841 WO1999032878A1 (en) 1997-12-19 1998-12-18 Liquid crystal sensors

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GB9726923A GB2332511A (en) 1997-12-19 1997-12-19 Liquid crystal sensors for sensing analyte molecules

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GB2332511A true GB2332511A (en) 1999-06-23

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CA (1) CA2314366A1 (en)
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012175214A1 (en) * 2011-06-21 2012-12-27 Sony Corporation Liquid crystal based sensor devices for detecting binding events or analytes at interfaces

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CN114674425A (en) * 2022-03-25 2022-06-28 西北核技术研究所 Cascade attenuation structure based on light pipe sampling, installation method and detection array

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US3927977A (en) * 1974-09-20 1975-12-23 Us Health Liquid crystal gas analyzer
US4040749A (en) * 1975-02-05 1977-08-09 Monsanto Research Corporation Organic vapor detection with liquid crystals
US4285697A (en) * 1978-09-26 1981-08-25 Neary Michael P Food spoilage indicator
US4975249A (en) * 1987-07-27 1990-12-04 Elliott Stanley B Optical and capacitance type, phase transition, humidity-responsive devices
IL93020A (en) * 1990-01-09 1995-06-29 Yeda Res & Dev Biosensors comprising a lipid bilayer doped with ion channels anchored to a recording electrode by bridging molecules
AU8720891A (en) * 1991-01-04 1992-08-17 Iowa State University Research Foundation Inc. An optical probe and method for monitoring an analyte concentration
US5543018A (en) * 1995-02-13 1996-08-06 Visible Genetics Inc. Method and apparatus for automated electrophoresis using light polarization detector

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Publication number Priority date Publication date Assignee Title
WO2012175214A1 (en) * 2011-06-21 2012-12-27 Sony Corporation Liquid crystal based sensor devices for detecting binding events or analytes at interfaces

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EP1047930A1 (en) 2000-11-02
CA2314366A1 (en) 1999-07-01
GB9726923D0 (en) 1998-02-18
WO1999032878A1 (en) 1999-07-01
AU1770399A (en) 1999-07-12

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