WO2018087523A1

WO2018087523A1 - A device and method for determining optical properties of a medium

Info

Publication number: WO2018087523A1
Application number: PCT/GB2017/053325
Authority: WO
Inventors: Jeremy HEBDEN; Danial CHITNIS
Original assignee: Ucl Business Plc
Priority date: 2016-11-08
Filing date: 2017-11-06
Publication date: 2018-05-17

Abstract

One example of the present approach provides a handheld, integrated device for determining the scattering and/or absorption properties of a medium by performing optical time- of-flight measurements. The device comprises a probe for inserting into the medium; and at least one solid state source configured to transmit an optical signal from the probe into the medium, and at least one solid state detector configured to receive said transmitted optical signal from the medium after propagation through said medium, subject to scattering and absorption within the medium. The at least one solid state source and the at least one solid state detector are configured to provide two or more propagation paths of different path-length through said medium. The at least one solid state detector is configured to detect timing information for the received optical signal to allow a time-of-flight to be determined for each of the two or more propagation paths.

Description

A DEVICE AND METHOD FOR DETERMINING OPTICAL PROPERTIES OF A MEDIUM Field The present application relates to a device for determining the scattering and/or absorption properties of a medium by performing optical time-of-flight measurements.

Background In many situations of interest, the primary interactions at optical wavelengths between a medium and light which is propagating through the medium are absorption and scatter. The degree to which each occurs in a synthetic medium can be easily manipulated by an

appropriate combination of scattering and absorbing agents within a solid or liquid matrix, such as by altering the quantities of the different agents.

As one example of the use of such measurements, a phantom may be developed to have the absorption and scattering characteristics of a biological tissue. The phantom can then be used in simulations to evaluate or calibrate the optical characteristics of medical equipment. Such phantoms are often used for applications in optical spectroscopy, imaging, and dosimetry, in which sources and detectors are placed on the surface of tissue with separations between a few millimetres and several centimetres. At commonly used near-infrared (NIR) wavelengths (approximately 700 to 950 nm), scatter dominates over absorption and light propagating more than a millimetre or so in tissue is rendered diffuse, i.e., all initial source beam directionality information is lost. Under these conditions it is sufficient for phantoms to mimic the so-called transport scattering properties of tissue, characterised by the transport (or "reduced") scattering coefficient denoted by μ₅', with units of mm^"1 [1 ]. Meanwhile absorption, which has much stronger wavelength dependence in tissue than scatter, is characterised by the absorption coefficient μ₃, also with units of mm^"1.

Many of the phantoms employed to date have been formed from liquids (usually water- based) in which suitable absorbing (e.g. inks, molecular dyes, and haemoglobin) and scattering (e.g. lipids, powdered solids, and microspheres) agents are added [2, 3, 4]. The construction of solid phantoms also often involves adding agents to a liquid matrix (e.g. resins, rubbers, gels, etc.) before solidifying (e.g. by the addition of a catalyst) [5, 6, 7, 8]. A broad variety of phantom recipes have been devised, and each usually relies on producing precise concentrations of absorbing and scattering substances, which have had their optical properties accurately characterised in advance. While strict adherence to the recipe is usually performed when preparing such phantoms in order to realise the intended optical characteristics to be simulated, it can be advantageous to check the optical properties of the fluid/solid during preparation. Some systems aiming to measure the scattering or absorption properties of phantoms or other objects using a measure of the intensity of light passing through or reflected by a turbid fluid have been proposed, most recently by Zhou et al [9]. However, measurements of intensity are notoriously influenced by the coupling between the optical sources/detectors and the medium - for example, a small stain, scratch, or air bubble on the surface of the probe would be likely to corrupt the measurement.

Other, primarily experimental, systems have been devised that required complex and expensive bench-top systems based on time-domain [10] or frequency-domain measurements [1 1 ]. Time-domain measurements (of times-of-flight of photons emitted by a pulsed source) and frequency domain measurements (of phase delay from an intensity-modulated source) are largely immune from variation in coupling. Various techniques for performing time-of-flight measurements for light transmitted across biological tissues and other highly scattering media are described in [12]. Such measurements have generally been performed with expensive, and usually bulky, bench-top systems which, although they offer the user flexibility in terms of experimental set-up (usually by allowing a user to arrange different parts of a modular system into a desired configuration), do not provide a good degree of flexibility in terms of portability or user manipulability.

One example of an existing system is described in EP 0710832-A1 , which presents a diffusion-based theory to demonstrate how scattering and absorbing coefficients can be extracted from time-of-flight surface measurements. This approach has primarily been used for the assessment of biological tissues, especially for measurements on living human subjects, and while effective in this context, the existing approach is relatively complex, and also somewhat restricted in the results that can be obtained.

Summary

The invention is defined by the appended claims.

Such an approach can be used for measuring or determining optical properties of media such as turbid fluids and has a wide range of applications, including medical applications - e.g. investigating and/or simulating biological tissues. Other examples of applications are in the food industry - e.g. for testing milk or other fluid food for reasons of quality control, such as to ensure consistency between batches and/or to identify the presence of foreign material (whereby the turbidity of these liquid foods can be tested against acceptable ranges). The approach can also be used for testing the performance of processes applied to fluids, for example, a purifying or cleansing process applied to water. The skilled person will be aware of many other examples in which measuring the properties of a turbid fluid or other suitable medium is desirable.

The approach described herein is well-suited to provide an affordable and portable apparatus offering a high level of flexibility for quickly determining the optical properties, including absorption and scattering, of a turbid fluid or other such medium. Such an apparatus may be used within a laboratory, but is also readily portable for off-site use in a wide range of environments. The apparatus is typically compact, which allows it to be utilised in relatively small samples of media, or for samples that might otherwise be difficult to access (e.g. if restricted to using larger equipment generally found in the laboratory).

One example of such a device comprises a housing, a source that emits photons, and a detector system for detecting photons emitted by the source. The device uses relatively small and low-cost components that can be provided together within the housing of the device, thereby providing a housing having an integrated source and detector system. In use, the device is immersed (at least partially) into a turbid fluid (or similar) to provide a measurement of the fluid's scattering and absorbing properties at one or more optical wavelengths.

Upon activation, the source emits photons into the turbid fluid. The detector system is configured to detect photons that are emitted by the source and subsequently scattered by the turbid fluid in order to provide an average time of flight of the photons from source to receiver (detector). This average time of flight is sensitive to the optical properties of the turbid fluid. The detector system is arranged so as to enable the detection of the time of flight of photons over at least two different separation distances with respect to the source/receiver. A combination of time-of-flight measurements for the at least two source-receiver separation distances can help to uniquely specify the absorption coefficient and the transport scattering coefficient of the fluid.

Also provided is a method for determining the scattering and/or absorption properties of a medium by performing optical time-of-flight measurements using an apparatus (such as described above, for example), including at least one solid state source and at least one solid state detector. The method comprises Immersing the at least one solid state source and the at least one solid state detector into the medium; transmitting an optical signal into the medium from the at least one solid state source immersed in the medium; and receiving, with the at least one solid state detector immersed in the medium, the transmitted optical signal after propagation through the medium, subject to scattering and absorption within the medium. The immersed at least one solid state source and the immersed at least one solid state detector provide two or more propagation paths of different path-length through said medium. The method further comprises the at least one solid state detector detecting timing information for the received optical signal, and determining a time-of-flight for each of the two or more propagation paths. The determined time-of-flight information for each of the two or more propagation paths may be used to determine the scattering and/or absorption properties of the medium.

Brief Description of the Drawings

The invention is now described by way of example only with reference to the following drawings in which:

Figure 1 schematically shows a device for detecting scattering and absorption properties of a medium in accordance with some embodiments of the present invention.

Figures 2A and 2B show experimental data for testing a component such as may be used in the device of Figure 1 in terms of reflected light.

Figures 3A and 3B show experimental data for testing a component such as may be used in the device of Figure 1 in terms of scattered light.

Figure 4 shows experimental data obtained by testing 369 different fluids using an approach described herein.

Figure 5 shows results from theoretical prediction for comparison with the experimental data shown in Figure 4.

Figures 6A, 6B, 6C and 6D show various combinations of source(s) and detector(s) for providing multiple path-lengths for use in an approach described herein.

Figure 7 shows an alternative implementation to the device of Figure 1 .

Figure 8 shows an alternative implementation to the device of Figure 1 .

Detailed Description

Aspects and features of certain examples and implementations of the present invention are described herein. Some aspects and features of certain examples and implementations may be implemented conventionally and these are not described in detail in the interests of brevity. It will thus be appreciated that such aspects may be implemented in accordance with any conventional technique known to the skilled person.

Light propagation through media, e.g., a turbid fluid, in which scattering dominates over absorption can be modelled using the time-dependent diffusion equation. Arridge et al. [13] show that for a point source and point detector separated by a distance d in an infinite homogeneous diffusing medium (where d » Μμ₃"), the mean time-of-f light of photons < t > is given by:

d²

< t > = ^■=- (1

2(r² + dy^_ac

where c is the velocity of light in the medium, and y is given by:

₂ c

^Y - 3(μ_α + μ> ) ⁽² Combining equations (

Thus the reduced scattering coefficient μ₃' can be calculated from a single measurement of < t > at a separation d between source and detector if both μ₃ and c are known.

In most cases, it is likely that c is known, or if not, it can be measured separately or estimated with reasonable precision. For present purposes, we assume that the absorption coefficient μ₃ is not known, and is a parameter of the medium to be measured. Accordingly, the absorption coefficient μ₃ (and reduced scattering coefficient μ₃") can be evaluated using measurements of < t > at two or more values of separation distance d. For example, for two measurements of mean time-of-f light < t > and < t >₂ obtained using two different separations cf| and d₂ respectively, the reduced scattering coefficient / can be eliminated from Equation (3) to obtain:

The corresponding value of the reduced scattering coefficient /v_s' can then be derived by inserting the value of the absorption coefficient μ₃ calculated using Equation (4) back into Equation (3). In other words, obtaining time-of-flight measurements over at least two known separation distances between a light source and a detector enables both the absorption coefficient /v_a and the reduced scattering coefficient μ_Ξ' \ο be determined.

The above analysis assumes ideal point sources and detectors in an infinite

homogenous medium. The assumption of infinite extent to a fluid medium is likely to be approximated in practice providing the distances from the source and from the detector to the nearest boundary of the container are at least a few times larger than the separation d. On the other hand, for any practical measuring device, the presence of optical components (i.e. the device itself) within the fluid will violate the condition of homogeneity. Consequently, a direct application of the above formulae may be unsuccessful, although it may be sufficient to utilise a pre-calibrated look-up table to convert time-of-flight measurements to values of /v_s' and / - In addition, although statistical uncertainties in measurements of < t > will reduce the accuracy and uniqueness of the solutions, both may be improved by combining data acquired at additional separations.

Figure 1 schematically shows an example of a device 100 for use in measuring the absorption and scattering properties of a medium in accordance with the above theory. The device 100 includes a housing 2, two emitter systems 4 and 6, a detector system 8, and a control and processing element 10 (e.g. a microcontroller, a processor, etc). Figure 1 also shows a display 12 communicatively coupled to the control and processing element 10.

The device 100 shown in Figure 1 has a "dipstick" configuration having two sections: a body section 2a, and a probe section 2b having a proximate end connected to the body section 2a and a distal end extending away from the body section 2a along a longitudinal axis. The body section 2a houses various control components, while the probe section 2b is shaped for insertion into the medium to be measured. Accordingly, the probe progressively narrows (e.g. is pointed or tapered) at the distal end to facilitate insertion into the medium; such insertion is also helped by the probe having a relatively small cross-sectional area (normal to the longitudinal axis) and a smooth exterior, e.g. with a circular or elliptical cross-section. The housing 2 in Figure 1 provides an integrated, one-piece device, and may be formed from plastic or the like. However, in other implementations, the body section 2a and the probe section 2b may have separate housings, with a suitable connection (e.g. optical fibres) extending between them.

The emitter systems 4, 6 in device 100 each have a light source 4a, 6a for emitting photons into a respective optical fibre 4c, 6c. The optical fibres 4c, 6d extend from inside the body section 2a down through the interior of the probe section, before respectively terminating at transmitters 4d, 6d. The transmitters may be implemented as passive couplings of the optical fibre to the external environment, e.g. through a suitable openings in the external housing 2, to allow the optical signal passing down optical fibres 4c, 6c to pass into the medium in which the probe section 2b is located. Note that the transmitters 4d, 6d are located at different positions in the probe section 2b, i.e. optical fibre 4c extends further down the probe section 2b towards the distal end than optical fibre 6c. This then provides two different distances for the time-of- flight measurements, as specified in Equation (4) above.

In one implementation, the light sources 4a, 6a are vertical-cavity surface-emitting lasers

(VCSELs), a form of light emitting diode (LED). However, it will be appreciated that any suitable light source may be used, e.g. another form of LED. In one implementation, the light sources 4a, 6a emit at a wavelength in the near infra-red (NIR) range, for example, at a wavelength between 830 to 870 nm, e.g. a wavelength of 850 nm. This wavelength is suitable for measuring the scattering and absorption of many types of medium. However, the light sources 4a, 6a can be arranged to emit light having any desired properties (wavelength, polarisation, etc) according to the particular medium and measurements to be made. The light source is typically monochromatic, e.g. to avoid complexities caused by variations in absorption with wavelength.

Each emitter system includes a driver 4b, 6b, which is communicatively coupled to the control and processing element 10. The drivers 4b, 6b are configured to drive (illuminate) the respective light sources 4a, 6a in response to signals received from the control and processing element 10. In some implementations, the drivers 4b, 6b may switch the light sources 4a, 6a on or off directly in response to a corresponding control signal received from the control and processing element 10. In other implementations, the drivers 4b, 6b may be preconfigured with one or more pulse patterns. The control and processing element 10 can then identify a particular pulse pattern to the drivers 4b, 6b, which then drive the light sources 4a, 6a in accordance with the identified pulse pattern.

The light sources 4a, 6a have a relatively small footprint; for example, the footprint for each driver is less than or equal to 5 x 5 mm, or 2 x 2 mm, or 1 x 1 mm (this may include the drivers 4b, 6b, if they are integrated into their respective light sources 4a, 6a). This small size for the emitters supports a compact overall design for the device 100.

The detector system 8 of Figure 1 comprises a receiver 8d for receiving photons from the medium surrounding the probe section 2a and passing them into optical fibre 8c. Like the transmitters 4d, 6d, the receiver 8d may be implemented as passive coupling of the optical fibre to the external environment, e.g. through a suitable opening in the external housing 2, to allow an optical signal to pass from the medium in which the probe section 2b is located into the optical fibre 8c.

The detector system 8 further includes a photodetector 8a, which in one implementation is a single-photon avalanche diode (SPAD). A SPAD provides a record of individual photon arrival times from the optical fibre 8c to a high accuracy (e.g. within a few tens of picoseconds) and so provides a record of the optical signal incident on receiver 8d. It will be appreciated that a SPAD is just one example of a suitable implementation for photodector 8a, and the skilled person will be aware of other potential implementations. The detector 8a typically has a relatively small footprint, for example, the footprint is less than or equal to 1 x 1 mm or 0.5 x 0.5 mm, or less, which again helps to support a very compact overall implementation for device 100. The detector system further includes signal processing electronics 8b, which in this implementation includes a time-to-digital converter (TDC). The signal processing electronics 8b may be integrated with the detector 8a, as shown in Figure 1 , or be provided as a standalone component. The TDC converts each of photon arrival events, as recorded by the SPAD detector 8a, into a corresponding digital time value, and these are then accumulated into a histogram indicative of the variation of incoming optical signal strength (intensity) with time (delay). The resulting histogram information is then passed onto the control and processing element 10 for further analysis to obtain estimates of absorption and scattering coefficients as per Equation (4).

As can be seen from Figure 1 , the optical fibres 4c, 6c, 8c are connected at their proximal ends to their respective light sources 4a, 6a and detector 8a and extend through the hollow interior defined by the elongated section 2b in a direction along the longitudinal axis towards the tip thereof. The optical fibres 4c, 6c, 8c are each positioned such that distal ends thereof (i.e. the end not connected to the light sources 4a, 6a or detector 8a) are provided at different locations along the longitudinal axis of the probe 2b. In this way, the distal end of the optical fibres provide respective source locations or detector locations at which the light sources 4a, 6a and detector 8a either emit or receive photons, as indicated by transmitters 4d, 6d and receiver 8d, respectively.

As mentioned above, the distal ends of the optical fibres 4c, 6c, 8c, namely transmitters 4d, 6d and receiver 8d, are each connected to a respective opening located within the probe section 2b such that the distal ends are exposed to the environment outside the probe section 2b. In this way, light can be transmitted from within the housing 2 to the external environment surrounding the housing, i.e. the medium being investigated, and vice versa for the incident light being received. It will be appreciated that the openings for transmitters 4d, 6d and/or receiver 8d, may be covered with a transparent material that does not absorb the light emitted by the light sources 4a, 6a e.g., a transparent material, but which protects the transmitters 4d, 6d and receiver 8d from direct exposure to the medium being measured.

The device 100 has transmitters 4d, 6d at two different locations along the longitudinal axis of the probe section 2b at which photons are emitted, and receiver 8d is at a third location along the longitudinal axis at which photons are received. Accordingly, this arrangement defines two separation distances, indicated as distances and d₂ in Figure 1 , whereby distances cf, and d₂ represent the distances of the transmitters 4d and 6d respectively from the receiver 8d. The distances and d₂ are typically of the order of a few millimetres, e.g., in the range from 1 to 20 mm, although smaller or larger separation distances may be used as appropriate. The detector system 8 of Figure 1 is configured to provide time-of-flight measurements to the control and processing element 100. Note that the first part of the analysis of these measurements may be performed within the detector system itself, e.g. within signal processing electronics 8b, and then the second part of the analysis may be performed within the control and processing element 10.

In some implementations, the transmitters 4d and 6d may be activated at different times, e.g. alternately, to measure the time of flight for distances d and d₂ respectively. In other implementations, transmitters 4d and 6d may be activated together, and the detector system 8 (and/or the control and processing element 10) can then look for two different delays in the received photons (one corresponding to the travel time over distance d the other to the travel time over distance d₂). One possibility is for each emitter system 4, 6 to emit a light signal having a different pattern in the time domain, using the drivers 4b, 6b, such that the pattern of light emitted by light source 4a is different from the pattern of light emitted from light source 6a. This can then allow the detector system 8 to separate out the two received signals from the different transmitters, somewhat analogous to a code division multiple access (CDMA) system.

Accordingly, the control and processing element 10 is able to compute an average (mean) time-of-flight for each distance d d₂. In other words, the processing element 10 computes a time-of-flight for the photons emitted by source 4a, < t > and a time-of-fight for the photons emitted by source 6a, < t >₂. Using these times-of-flight, the processing element 10 is able to utilise Equations (3) and (4) to determine the absorption coefficient μ₃ and reduced scattering coefficient μ₅'. As shown in Figure 1 , the values for these coefficients derived from the time-of-flight measurements may be provided on a display 12 communicatively coupled to the device 100. Hence, the device 100 described above is capable of providing an

instantaneous (or near instantaneous) measurement of the absorption and scattering properties of a medium.

It will be appreciated that although the coupling shown in Figure 1 is a wired connection between the processing element 10 and the display 12, there may alternatively be a wireless connection between the display 12 and the housing 2, or else device 100 itself may directly incorporate the display 12 within housing 2. Another possibility is that the device 100 communicates (typically wirelessly, e.g. using Bluetooth) with a separate device, such as a smartphone, personal computer, laptop, notepad, etc, which can then be used to display the results from device 100. In some cases, this separate device might also be used, at least in part, to control the device 100, e.g. to program settings, etc.

One implementation of device 100 is based on the VL6180X proximity sensor available from ST Microelectronics, which is primarily intended to use photon flight time information to measure the distance between the sensor and a reflecting surface [14]. (This sensor is mainly targeted at the mobile telephone market, to allow a handset to determine if it is being held close to the ear, i.e. as for a conventional telephone handset, in which case the screen no longer needs to be illuminated). This sensor incorporates a VCSEL LED with an emission wavelength of 850 nm (i.e. only a single emitter), and a SPAD detector. The LED and the photodetector are both provided on the same (single) chip, about 3.3 mm apart. The footprint of this chip is 4.8 x 2.8 mm. The sensor is relatively low-cost (approximately 2 US dollars), and is provided with an evaluation kit that supports a USB link to a personal computer or other such device.

The specified distance range for the reflecting surface is 0 to 100 mm with a resolution of 1 mm at rate of 10 Hz. Ranging beyond 100 mm is quoted as possible, but with less reliability. Note that in air, light travels approximately 0.3 mm per picosecond, hence a distance of 30 mm to the reflecting surface (which implies a total light travel distance of 60 mm), would have a corresponding time-of-flight of approximately 200 picoseconds. (In media other than air, the propagation time would be longer due to increased refractive index). For use in the present context, the detector is looking for a scattered signal rather than a reflected signal; the former will generally be more diffuse (less of a sharp pulse) than the latter, since the received signal will, in aggregate, represent the result of many different scattering paths through the medium.

The measurement accuracy of the VL6180X proximity sensor in air was assessed by supporting the sensor vertically while a parallel sheet of white board was held at a known distance from the sensor. Data from the sensor were recorded as the board was translated in 5 mm steps away from the sensor, and averaged for 100 samples (equal to 10s) at each position in order to improve the accuracy of the measurement. The recorded values of distance and photon count rate are plotted against the true sensor-board distance from the target in Figures 2A and 2B respectively. Error bars represent the standard deviation of the 100 samples at each position. The plot of true versus measured distance exhibits a strong linearity with a slope of 0.999 ± 0.01 1 and an intercept of zero (linear fit shown in Figure 2A). The intensity data exhibits a rapid decrease in the detected signal due to the divergence of the emitted light and non-specular reflectance of the white board.

The ability of the VL6180X proximity sensor to measure photon flight time across a region of highly scattering fluid was assessed using a tank of intralipid. Intralipid is a milk-like commercially available lipid emulsion which is produced as an intravenous nutrient, and is commonly used as a phantom material [2]. The rectangular tank had a surface area of 200 χ 130 mm, and was filled to a depth of 50 mm with a pre-calibrated solution of intralipid to produce a fluid with a transport scatter coefficient of 1 .0 mm^"1 and an absorption coefficient of 0.0043 mm^"1 at the sensor wavelength of 850 nm.

To facilitate measurements in the fluid for different source-detector separations, a small customised connector was utilised (3D printed in black plastic) to secure the (proximal) ends of two short (37 mm) lengths of un-terminated polymer optical fibre in contact with the source (LED) and detector respectively. The other (distal) ends of the fibres were held apart using a spacer, formed from a thin plastic rod with two holes separated by a fixed distance. A set of spacers were utilised to provide different (fixed) distances of separation. The distal ends of the fibres were then immersed to a depth approximately halfway between the top and bottom surfaces of the fluid, with the fibre in contact with the source acting as an optical transmitter, and the fibre in contact with the detector acting as a receiver. Data were recorded for 10 seconds using spacers that provided separations of 4, 6, 10, 14, and 18 mm respectively.

The resulting data from these experiments are shown in Figures 3A and 3B. In particular, Figures 3A and 3B respectively show the (a) distance and (b) intensity values recorded in intralipid for five different fibre separations. It can be seen from Figure 3A that the distance measured by the sensor exhibits a smooth, near-linear increase with fibre separation, while the intensity shows in Figure 3B a corresponding exponential-like decrease. At larger separations, when the intensity (photon count rate) falls well below 1 Mcps, the distance measurements become erratic.

The continuous line in Figure 3A represents the theoretical mean photon path-length (c < t >) calculated using Equation (1 ). There are two reasons why a close match between the measured and modelled distances is not expected. First, and most importantly, the sensor was designed to measure distances in air, and not to provide a distance value from a (deliberately) temporally broadened signal from heavily scattered light. Details of the measurement technique and signal processing scheme employed by the VL6180X sensor are not available, but it is expected that the sensor identifies the peak (mode) of the temporal distribution of the returning photons, rather than the mean. Second, the measurement geometry does not closely approximate a point source and point detector in an infinite medium. In principle this could be improved using longer and thinner fibres embedded in a larger tank, although the finite depth range of the sensor restricts the maximum length of the fibres that can be employed.

An experiment was now performed using dual sensor measurement in a turbid fluid. In particular, two independent VL6180X sensors were utilised, mounted on different expansion boards. A pair of fibres was attached to each sensor (in the same manner as described above for producing the results of Figures 3A and 3B). A spacer of 3 mm for the transmitter-receiver distance was used with one sensor, and a spacer of 6 mm for the transmitter-receiver distance was used with the other sensor. The two sensors were then immersed into the same tank, approximately 90 mm apart. The sensors were operated consecutively, so that light emitted by one sensor was not detected by the other. Measurements were acquired for solutions with nine different intralipid concentrations, corresponding to transport scattering coefficients (at 850 nm) between 0.4 mm^"1 and 2.0 mm^"1 , increasing in steps of 0.2 mm^"1. For each intralipid concentration, an aqueous solution of NIR-absorbing dye (ICI S109564) was manually injected and stirred into the fluid to increase its absorption coefficient (at 850 nm) in steps of 0.001 mm^"1 to 0.04 mm^"1. Measurements were acquired from both sensors, averaging over 100 samples, to produce pairs of distance measurements ml and m2 for 9 x 41 = 369 fluids with distinct optical properties.

Figure 4 is scatter plot of the distance measurements acquired using the two fibre separations for the 369 different fluids. In particular, Figure 4 displays the distance values obtained from the time-of-flight measurements using one sensor (ml with fibre separation d1 = 3 mm), plotted against the distance values obtained from the time-of-flight measurements using the other sensor (m2 with d2 = 6 mm). A constant offset is subtracted from both sets of measurements, equal to the distance recorded when the two ends of the fibres are coupled together (i.e. representing zero flight time). As expected, Figure 4 shows nine lines of 41 points, each point corresponding to a different combination of values for μ₃ and μ₃'. The spacing between points within a given line decreases significantly as μ₃ increases, and to a lesser extent the spacing between lines tends to decrease as μ₃' increases. Accordingly, for a given intralipid concentration (i.e. fixed μ₃), the measured distances, both ml and m2, generally decrease for increasing absorption μ₃. This is to be expected, because the increased absorption reduces the influence of longer overall paths (because these are attenuated due to the absorption).

Conversely, for a given dye concentration (i.e. fixed μ₃), the measured distances, both ml and m2, generally increase for increasing μ₃'. Again, this is to be expected, because the increased scattering increases the average path-length taken by the photons.

By comparison with Figure 4, Figure 5 shows corresponding theoretical values of mean pathlength (c < t >) calculated using Equation (1 ) for the same two source-detector separations and the 369 pairs of optical properties used experimentally. The predicted ranges of pathlengths for the two sensors are similar to those exhibited experimentally, but some differences between theory and experiment are inevitable for the reasons stated above. It is worth observing however that the measured points show better separation than the theoretical predications, which in principle would allow better determination of μ₃ and /v_s' for any given measurement.

A comparison between Figures 4 and 5 shows that, despite their broad similarities, in this experimental set-up, the theoretical model is not sufficient to enable the optical properties μ₃' and μ₃ to be extracted from the distance (time-of-flight) measurements by applying Equations (3) and (4) directly. Nevertheless, since there is relatively little overlap of data (except at very high μ₃) in Figure 4, this means that empirical models can be applied to enable reasonably accurate predictions of both properties to be extracted for an arbitrary pair of distance values. For example, a look-up table can be generated by extrapolating between points on the surfaces of plots of μ₅' (< t > < t >₂) and μ₃ (< t >i , < t >₂).

Figures 6A-6D show in schematic form a number of different configurations for performing time-of-flight measurements as described herein. In these diagrams, a light source (transmitter) is represented by an S, while a light detector (receiver or destination) is

represented by a D, and different subscripts are used to enumerate between different sources or detectors.

For example, Figure 6A schematically shows the positions of two light sources, labelled Si and S₂, and the position of a detector labelled D which are arranged to provide two separation distances, d and d₂. It will be appreciated that this configuration corresponds with the configuration (but not the specific component locations) of the detecting device 100 of Figure 1 . Figure 6B can be regarded as a converse arrangement to that of Figure 6A, in which two detectors labelled D and D₂ are provided at different separation distances (di and d₂) from a single source labelled Si . In the implementation of Figure 6B, both detectors may detect the same light pulse from source S_{1 5} but will do so at different times owing to the dependence on the separation distance c/ of the time-of-flight.

Figure 6C schematically shows another alternative configuration involving separate source-detector pairs, the first labelled Si and D the second labelled S₂ and D₂. The first and second pairs have respective source-detector separation distances of d and d₂, as shown in Figure 6C. This corresponds to the configuration used to generate the experimental data shown in Figure 4.

Figure 6D shows another configuration involving a single source labelled Si and a movable detector labelled D Figure 6D shows a first separation distance d between the source Si and detector D and then a second separation distance, d₂, which is achieved by moving the detector D in the direction of the arrow A until it reaches a position shown in Figure 6D indicated by dashed lines. This configuration corresponds to that used to obtain the measurement data of Figures 3A and 3B.

If two or more sources are used, then a detector needs to be able to distinguish between the signals received from a given source. As described above, this can be achieved for example by operating the different sources consecutively, one after the other, or at the same time, but each having a distinct temporal pattern of emission, e.g. a sequence of pulses with timings specific to that source. Another possibility in the context of Figure 6C is that the two detectors are much closer to their paired source than to the other source (and may perhaps be shielded from the latter), such that little or no interference occurs. It will be appreciated that using spatial or temporal separation to avoid interference assumes that the medium is generally constant in space (homogeneous) and time, which in most cases is a reasonable assumption (to the extent required by the measurements). For example, time-of-flight measurements are not usually sensitive to the precise time at which measurement is performed. In other words, it is plausible to measure the time-of-flight for separation distance d several seconds (say) before measuring the time-of-flight for separation distance d₂. Of course, if spatial or temporal variations are present, then this can be accommodated, for example by having different sources simultaneously emit different patterns of optical signal, as discussed above.

In each of Figures 6A to 6D, two different separation distances are utilised and time-of- flight measurements are made for each of these two separation distances. However, the accuracy of the estimated absorption and scattering coefficients can be improved by obtaining time-of-flight measurements at additional separations distances, typically by including more detectors and/or more sources. For example, in Figure 6A, additional separations might be provided by including additional sources at different (distinct) separations from the detector, while in Figure 6B additional separations might be provided by including additional detectors. It is also possible to add further detectors to the configuration of Figure 6A, or further sources to the configuration of 6B. In the configuration of Figure 6C, additional pairs of sources and detectors might be provided (or any desired combination of additional sources and detectors, not necessarily as pairs). Indeed, the configuration of Figure 6C already supports potential additional distance measurements, based on the transmission paths from D to S₂ and D₂ to Si . In general, having equal numbers of detectors and sources can provide the greatest number of overall transmission paths for a given number of components. In the configuration of Figure 6D, additional separations may be achieved by moving the existing source and/or detector to other positions. This avoids the need for any additional equipment, albeit the measurements are likely to take longer to complete.

In some implementations, the number of separations may be increased by splitting the output from a single source, e.g. by using a beam splitter or equivalent. For example, the configuration of Figure 6A might be implemented using a single physical source, whose output is then split across two or more transmitters to generate multiple different separations. It may also be possible to combine multiple received signals for sending to a single photodetector, for example when implementing the configuration of Figure 6B (providing the combined signals can be distinguished at the photodetector, e.g. based on relative timing, or distinct modulation patterns imposed onto the individual signals).

The skilled person will be aware of many different combinations of the approaches set out above for providing additional separations. If time-of-flight measurements are available for three or more separations, then μ₃ and /v_s' can be determined on a statistical basis, as a best fit to the overall set of measurements. This can also give an indication as to the likely accuracy of the results. Note that having the sources and detectors configured to also provide multiple different measurements at any given separation can likewise help to improve accuracy on a statistical basis (assuming that measurements for at least two different distances are available).

Various other mechanisms are available for improving or enhancing the measurements. For example, rather than performing all measurements at a single wavelength, multiple different wavelengths may be used. Note that such measurements might be desired to characterise the wavelength dependency of μ₃ and μ_Ξ' (rather than necessarily to improve the accuracy of measurement at a single wavelength). This wavelength dependency of μ₃ and μ_Ξ' may be used for various purposes, such as to try to identify the chemical components of a given medium.

Another mechanism to help improve the measurement performance is to exploit more fully information about the photon time arrivals. Thus in the measurements shown in Figure 4, the available output from the detector regarding time-of-flight was a single measurement for mean (or peak) delay. However, if the complete set of photon arrival times is available, then this can be processed to obtain additional information. For example, the spread of arrival times is indicative of the amount of scattering, since more scattering will tend to increase this spread. Therefore parameters such as mean and variance, or more complex statistics reflecting the overall distribution of arrivals times, such as represented by a histogram of count against time, could be compared with theoretically and/or empirically determined parameters, to give a more reliable estimate of the mean path length from any given measurement (or to estimate directly the values of μ₃ and μ₃).

Figure 7 shows another example of a measurement device 200 using the approach described herein. The detecting device 200 shares some similar components with the detecting device 100. Accordingly, like reference signs indicate like components and the descriptions thereof will not be repeated here for reasons of brevity. The device 200 of Figure 7 includes a housing 202 which is cylindrical in shape and defines a hollow interior. The housing 202 is provided in a two-part configuration and comprises a body section 202a and a grip section 202b, although the housing 202 may be formed from any number of parts. The body section 202a incorporates two emitter systems 4, 6, a detector system 8, and a processing element 10. The body section 202a is substantially cylindrical and includes a flat surface at one end of the longitudinal axis in which windows or openings 202c are provided. In a similar way to Figure 1 , optical fibres 4c, 6c, 8c connect the openings 202c to the light sources 4a, 6a and the detector 8a. The body section 202a is also provided with a threaded coupling (not shown) at the end opposite that containing the openings 202c for allowing the grip portion 202b to couple to the body section 202a. The grip section 202b has a hollow interior to receive a power source 214, such as a battery. The operation of the device 200 is generally the same as the operation of device 100 in terms of how the estimates of the absorption and reduced scattering coefficients are determined. Figure 8 shows another implementation of the approach described herein. In this example, the device is provided with a support element 300 to hold the device 100, 200 (rather than the device being handheld). The support element 300 of Figure 8 has one or more moveable sections 310, 320 coupled together with a hinge 330. One movable section 310 supports, at one end, the device 100, 200. The other section 320 is fixed to a base 340 at the end opposite the hinge 330. In this arrangement, the support element 300 can be positioned to hold the device at an appropriate location within a container 350 or the like. The support element 300 allows the device to be supported within the container 350 to obtain estimates of the absorption and scattering coefficients.

As described above, the recent advent of low-cost solid-state time-of-flight technology, primarily intended for the mobile phone market, such as the VL6180X proximity sensor, has been exploited for very different purposes. In particular, mass production of the VL6180X proximity sensor, resulting in a very low cost, has allowed experimental confirmation that such technology provides a viable approach for characterising the optical properties of media such as turbid fluids. This existing sensor has certain limitations for such a significant change of use - for example, it is not designed to measure the temporal broadening produced by scatter, and it may not compute a true measurement of mean flight-time (but rather determines peak time, or some other similar parameter). Furthermore, the wavelength of operation is fixed at 850 nm, the emitted power is relatively low, and the detection area is relatively small; these last two factors in practice limit the distance measurement range, and have resulted in the use of relatively small source-detector separations of d1 = 3 mm and d2 = 6 mm. One potential consequence of these small separations is that measurements at the lowest values of μ_Ξ' may not have met the diffusion equation condition that d» 1//V- (which is likely to explain the observed departure between the experimental results and the theoretical model as μ₃' decreases).

Nevertheless, despite these limitations, the combination of two VL6180X proximity sensors (such as per the configuration of Figure 6C) has enabled time-of-flight measurements to be acquired. Such measurements appear to be capable of uniquely characterising absorption and transport scattering properties, e.g. of turbid intralipid-based solutions (at least when the absorption is comparatively low).

Furthermore, it is noted that ST Microelectronics have recently released their VL53L0X proximity sensor [5]; this has a larger specified range of 2 metres, and so should be able to accommodate larger source-detector separations, although it emits at 940 nm, which is less suitable for NIR spectroscopy and imaging. More generally, recent advances in the field of miniaturised time-correlated single photon counting (TCSPC) devices [15] and solid-state sources of very short pulses of light has already begun to be explored in NIR spectroscopy and imaging applications, particularly by research groups in Milan [16] and Lausanne/Zurich [17]. Accordingly, it is expected that the available hardware for performing the time-of-measurements described herein is likely to become increasingly widespread and flexible over the next few years.

The approach described herein can be used to measure properties, specifically scattering and absorption properties, of an optical medium, which may, for example, be a turbid fluid. Turbid fluids are typically formed based on fluids having particles suspended therein, and are produced or used in a number of different industries for a variety of reasons. For instance, the development and evaluation of instruments for biomedical optics applications frequently requires the use of objects which mimic the optical properties of biological tissues, known as phantoms [1 ]. The approach described herein can be used, for example, to assess such phantoms, e.g. to compare them with genuine biological tissues. Note that "optical" in this context is not specifically limited to visible wavelengths, but includes neighbouring regions of the electromagnetic spectrum, such as soft UV and near IR, in which regions it may be useful to be able to measure scattering and absorption coefficients in this manner.

Generally, there has been described herein a device which is configured to obtain time- of-flight measurements of photons passing through a medium such as a turbid fluid at two or more separation distances between the detector(s) and source(s). Using the fact that two time- of-flight measurements at different separation differences can uniquely characterise the absorption and reduced scattering coefficients of a turbid fluid (according to theory), such a device can be kept relatively simple, small, and low in cost. This enables a user to be able to handle the device with relative ease to obtain quickly estimates of the properties of the turbid fluid.

The device described herein can be formed as a "dipstick" with a geometry suitable for quickly characterising optical media, for example, such as shown in Figures 1 and 7. Such a device has applications for characterising scattering fluids or media such as paint, milk and other liquid foods, industrial solvents, and liquid pharmaceuticals. More generally, the device may be utilised in respect of any medium into which it can be suitably inserted, even if not a conventional fluid - such as emulsions (suspensions of minute droplets of one fluid in another), gels, pastes, creams, etc. In some cases, a larger device might be utilised, such as shown in Figure 8. In some implementations, the transmitter(s) and receiver(s) might be formed on different components, which can be moved relative to one another, for ease of positioning and measurement.

One example of the use of a device described herein is in the context of creating phantoms for evaluating of medical instruments. The detecting/measuring device can be inserted into a suitable turbid fluid/gel/simulated tissue etc forming the phantom, which may include components having different absorbing or scattering properties. In this way, when the device is inserted into the mixture, a measure of the absorption and scattering properties of the fluid can be found without prior characterisation of the actual properties of the scattering and absorbing agents, meaning that different quantities of agents can be added to the mixture to obtain the desired properties (as indicated by the device, and as corresponding to a desired tissue to be simulated) without precisely following a specific recipe. This can allow such phantoms to be prepared quickly and accurately using a simple dipstick-type detecting device such as shown in Figures 1 and 7.

In the device of Figure 1 , the two sources (emitters) and the detector are integrated into a single unit, and may, if so desired, be provided on a single semiconductor chip. This can have certain advantages, for example, in controlling the relative operational times of the sources and detector. However, the source(s) and detector(s) may be provided on different or individual chips as desired, which may, for example, allow more flexible configurations that can be altered according to the requirements of any given measurement. The different chips may be mounted on a single circuit board (or flex circuit).

As described herein, photons emitted by a light source propagate through the turbid fluid (or other medium) and are received by the detector system. The time-of-flight of photons from source to detector is a function of the properties of the turbid fluid, in particular, the reduced scattering coefficient μ₃', the absorption coefficient μ₃ and the velocity of light within the medium. N.B. the velocity of light can be separately determined or measured - e.g. the device shown in Figure 1 , for example, might incorporate additional functionality to measure the speed of light in the medium. Multiple source-detector separations are employed, with combinations of three or more distance measurements likely to yield superior accuracy in the determination of both coefficients. In general, the distances used for the measurements should satisfy the diffusion equation condition that d» 1/μ₃'. Example path-lengths are in the range 2-200mm, or 3-

150mm, or 8-100mm; the path lengths used for any given measurement are dependent on the apparatus (e.g. the strength of the emitted signal, and the sensitivity of the detector) as well as the medium being measured (e.g. the amount of absorption and scattering).

The emitter and detector systems utilised herein typically have dimensions small enough to allow these components to be integrated into a single housing that is small enough for a user to grip with one hand and to be able to freely manipulate the device with one hand. Providing the components in such an integrated device avoids the complexities involved in setting-up bench-top equipment having multiple individual (separate) components.

The immersive emitter and detector systems utilised herein for assessment of the properties of fluids has important advantages over existing surface-based measuring devices in two main respects. Firstly, surface-based devices have a more complex theory (to accommodate the boundary) compared with immersed devices (assuming a container is sufficiently large that the medium can be modelled as infinite - which in practice is often a reasonable assumption). Furthermore, even though the device itself represents an additional factor for an immersed device, this additional factor is normally relatively stable and

reproducible whenever the device is immersed in a given medium, thereby supporting the use of a pre-calibrated system as described above. In contrast, existing surface-based devices for the measurement of scattering and absorption have a dependency on the precise geometry of the boundary, including its shape, plus any curvature and/or texture. In addition, surface-based devices have a dependency on the accuracy of the placement of the measuring device, including whether the device is exactly aligned with (e.g. parallel to) the surface, and also whether the device is slightly above or below the surface level of the medium being

investigated. Consequently, surface-based devices are mainly employed in the laboratory, where a precise set-up is feasible (otherwise the results become less reproducible).

Secondly, existing surface-based measuring devices primarily measure the boundary region of the medium. In contrast, the immersive devices described herein can be inserted to different depths within a medium. Not only can this provide a more reliable assessment of the bulk of the medium (e.g. away from potential contaminants that may be located at the surface), but it also allows a measurement of the degree of homogenisation of a fluid, which is of specific relevance (for example) to the characterisation of emulsions such as milk and of particulate colloids such as paint.

Further particular and preferred aspects of the present invention are set out in the accompanying independent and dependent claims. It will be appreciated that features of the dependent claims may be combined with features of the independent claims in combinations other than those explicitly set out in the claims.

REFERENCES

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Claims

1 . A handheld, integrated device for determining the scattering and/or absorption properties of a medium by performing optical time-of-flight measurements, the device comprising:

a probe for inserting into the medium;

at least one solid state source configured to transmit an optical signal from the probe into the medium, and at least one solid state detector configured to receive said transmitted optical signal from the medium after propagation through said medium, subject to scattering and absorption within the medium;

wherein the at least one solid state source and the at least one solid state detector are configured to provide two or more propagation paths of different path-length through said medium; and

wherein the at least one solid state detector is configured to detect timing information for the received optical signal to allow a time-of-flight to be determined for each of the two or more propagation paths.

2. The device of claim 1 , wherein the device is configured to transmit two or more optical signals into the medium from two or more respective transmitting locations on the probe.

3. The device of claim 2, wherein a single solid state source is configured to transmit the two or more optical signals into the medium.

4. The device of claim 3, wherein the single solid state source is configured to transmit in turn an optical signal from each respective location.

5. The device of claim 2, wherein the device comprises a respective solid state source configured to transmit each optical signal into the medium.

6. The device of any of claims 2 to 5, wherein the two or more optical signals are received at a single receiving location on the probe, wherein the single receiving location has a first distance from a first one of the transmitting locations and a second distance, different from the first distance, from a second one of the transmitting locations.

7. The device of claim 6, wherein the solid state detector is configured to distinguish between a first signal received at the receiving location from a first one of the transmitting locations and a second signal received at the receiving location from a second one of the transmitting locations by detecting first and second, different, modulation patterns imposed respectively on the first and second signals.

8. The device of any preceding claim, wherein the at least one solid state source and the at least one solid state detector are mounted on a single circuit board.

9. The device of claim 8, wherein the at least one solid state source and the at least one solid state detector are integrated in a single semiconductor device.

10. A device for determining the scattering and/or absorption properties of a medium by performing optical time-of-flight measurements, the device comprising:

at least one solid state source configured to transmit an optical signal into the medium, and at least one solid state detector configured to receive said transmitted optical signal from the medium after propagation through said medium, subject to scattering and absorption within the medium;

1 1 . The device of any preceding claim, wherein the solid state detector detects individual photon arrival times.

12. The device of claim 1 1 , wherein the time-of-flight is determined based on a peak or mean of the photon arrival times.

13. The device of claim 1 1 , wherein the time-of-flight is determined based on a histogram of the photon arrival times.

14. The device of any preceding claim, further including one or more optical fibres for conveying the optical signal from the solid state source to one or more locations for transmitting the optical signal into the medium.

15. The device of any preceding claim, further including one or more optical fibres for conveying the optical signal to the solid state detector from one or more locations for receiving the optical signal after propagation through the medium.

16. The device of any of the preceding claims, further comprising an internal power source for providing power to the device.

17. The device of any of the preceding claims, further comprising a handle portion for allowing a user to grip the device and manipulate the device.

18. The device of any of the preceding claims, wherein a source and/or a detector is movable to provide additional propagation path-lengths.

19. The device of any preceding claim, wherein the different sources are configured to emit photons in accordance with different predetermined temporal patterns, and wherein the detector system or processing element is configured to differentiate photons emitted by the first source from those emitted by the second source by associating detected photons with each

predetermined temporal pattern, thereby allowing the detector system to distinguish between signals from different sources.

20. The device of any preceding claim, wherein the device further includes a display integrally formed with the housing for displaying determined properties of the medium.

21 . The device of any preceding claim, wherein the path-length through said medium is typically in the range 2-200mm, preferably 3-150mm, preferably 8-100mm.

22. A method for determining the scattering and/or absorption properties of a medium by performing optical time-of-flight measurements using an apparatus including at least one solid state source and at least one solid state detector, the method comprising:

Immersing the at least one solid state source and the at least one solid state detector into the medium;

transmitting an optical signal into the medium from the at least one solid state source immersed in the medium;

receiving, with the at least one solid state detector immersed in the medium, said transmitted optical signal after propagation through said medium, subject to scattering and absorption within the medium, wherein the immersed at least one solid state source and the immersed at least one solid state detector provide two or more propagation paths of different path-length through said medium;

the at least one solid state detector detecting timing information for the received optical signal; and

determining a time-of-flight for each of the two or more propagation paths.

23. The method of claim 22, further comprising using the determined time-of-flight information for each of the two or more propagation paths to determine the scattering and/or absorption properties of the medium.

24. A detecting device substantially as described herein with reference to the accompanying drawings.