Optical fibre instrumentation for point of care diagnostics

Lead Research Organisation: Cranfield University
Department Name: Sch of Aerospace, Transport & Manufact

Abstract

Enhanced prediction and diagnosis in real time and at the point of care is recognised as a means of addressing national and global health challenges, with the development of sensors to detect and measure biomedical markers being a strategic priority. Chemical compounds excreted from the human body are believed to reflect certain metabolic conditions as well as the blood gas content. The changes in concentration of some compounds, referred to as biomarkers, and chemical composition in human samples such as breath, blood, urine, sweat and saliva can be linked to particular diseases and have been intensively used in medicine for early and minimally invasive diagnosis. There is considerable interest in the development of sensor devices to identify compounds both in vivo and ex vivo that can facilitate non-invasive diagnosis.

Sensing techniques based upon the use of optical fibre devices to probe the optical characteristics of nanomaterials that exhibit changes in their optical properties upon exposure to targeted chemical species are particularly attractive, in light of their potential high sensitivity, selectivity, the ready ability to multiplex arrays of sensors, and the prospect for remote sensing. Optical fibre grating devices, which are based upon a periodic perturbation of the refractive index of the core of the optical fibre, will be exploited as the sensing platform. Fibre gratings facilitate the controlled coupling of light between modes of the optical fibre structure at specific resonant wavelengths, with the wavelength showing sensitivity to perturbation of the fibre. Such devices have been applied extensively as sensors.

The techniques that will be exploited here further develop the methods pioneered at Cranfield that was awarded First Prize in the Frontier Science and Technology category of the 2004 National Measurement Awards, and further developed in a collaboration between Cranfield and Kitakyushu Universities, involving the deposition of nanoscale, functional coatings onto the surface of optical fibre devices.

The project brings together a multidisciplinary team with expertise in photonics, chemistry, analytical science and health care delivery. This will exploit cutting edge sensing techniques and materials to facilitate the design, fabrication and characterisation of the sensors, with the aim of developing a diagnostic instrument for use by a non-specialist in a clinical setting. The output and impact of the research will be maximised through functional testing of the instrumentation in a clinical environment.

Thus this proposal will develop a point-of-care (POC) device that will be assessed for accuracy, sensitivity, reproducibility, reliability and ease of use in a clinical setting. This will be achieved by (i) taking a fibre optic ammonia sensor previously demonstrated by the Cranfield and Kitakyushu teams, optimising its sensitivity and improving its immunity to application- specific interference from temperature and humidity, (ii) benchmarking its performance against established technologies, (iii) developing it into a prototype point-of-care device for use by non-specialist clinical staff, (iv) demonstrating the generic nature of the sensor platform and instrument by using it to monitor other biomarkers (e.g. acetone) and (v) demonstrate a multiplexed sensor capable of monitoring simultaneously a number of analytes, in this case those identified in (iv).

Planned Impact

Enhanced prediction and diagnosis of diseases in real time and at the point-of-care, the theme of this proposal, is recognised by the government funding agencies (e.g. TSB and EPSRC) as a means of addressing national and global health challenges, with the development of sensors to detect and measure biomedical markers being a strategic priority. It is recognised that the availability of low cost, robust, non-invasive technologies capable of providing early diagnosis will impact on the well-being of the population, which will have a positive impact on economic activity and productivity, and reduce healthcare service spending. The major beneficiaries of this research will be patients and Clinicians. The developed instrument would allow faster, non-invasive and reliable diagnostics of diseases.

The sensor elements themselves can be reused if appropriate. For certain analytes the response is reversible, while for others the sensors can be washed and the response restored (to the original analyte, or to a different analyte) by re-infusing AN appropriate functional material. This may offer a significant cost benefit and have impact for use in developing countries.

Publications

10 25 50
 
Description The project investigated the development of an optical fibre based sensor for use for the measurement of chemicals in breath samples, with the aim of exploring the use of the technology within a clinical environment as a point-of-care diagnostic tool. The sensor technology, the optical fibre long period grating, can be made selectively sensitive to a chemical of interest by applying a suitable coating, which changes its optical properties in response to the chemical, to the surface of the fibre. Here the focus was on the detection of ammonia, a biomarker for a number of conditions, using a porphyrin compound, which changes its absorption spectrum and refractive index on exposure to ammonia, as the sensitive material. The research explores a number of key aspects of sensor and instrumentation development: repeatable and reliable fabrication of sensor elements, the coating material and the means for its deposition, the means for packaging the sensors, the mitigation of the influence of interfering effects - primarily temperature and humidity, the approach to interrogating the sensor and to communicating the information to the user. The fabrication of the senor elements involves the exposure of the optical fibre to the output from a UV laser source to create a periodic modulation of the refractive index of the optical fibre. The sensitivity of the device is highly dependent upon the period of the modulation (of order 100 microns, with a requirement for control to within 100 nanometers), but is also influenced by the amplitude of the modulation (which is controlled by the UV laser intensity). A new methodology for the sensor fabrication, whereby the device is fabricated with a relatively low power UV laser beam, but the process is repeated a number of times, allowed the fabrication process to be stopped when the desired device characteristics had been achieved, increasing significantly the repeatability of the sensor fabrication. The coating material and approaches to its deposition onto the optical had been explored in previous work, and involves the deposition of a base mesoporous coating of silica nanospheres, followed by the infusion of the chemically sensitive material. The use of 3D printing technology was explored when considering the packaging of the sensor, involving development of means for embedding the optical fibre in 3D printed plastic structures. A key issue considered is the influence of the plastics on the sensor performance - do the chemicals of interest stick to the plastic and reduce the signal, or does the plastic give off interfering chemicals? It was found that the plastic can have a significant influence. The VOCs emitted from commonly used 3D printed plastics have been assessed showing that the concentration of VOCs emitted makes them unsuitable for this application. In addition, there was a tendency for the chemical of interest, ammonia, to bind to the surface, reducing the concentration available for detection by the sensor and thus compromise the measurement capability. An alternative new system, using custom blown glass components was designed and fabricated. The relatively long timeframe for the interaction of ammonia with the porphyrin, upto 30 mins, exposed considerable challenges associated with condensation and sealing of the system and control of temperature. The mitigation on interfering parameters involved the use of sections of fibre sensitised differently. Both sections have the base mesoporous coatings applied, but the chemically sensitive material is added to only one of them. A number of configurations were explored, with the most promising approach (in terms of the processing of the data) relying upon the sections of fibre containing LPGs of slightly different period, allowing their multiplexing in the wavelength domain. A key feature of breath analysis systems is the requirement for the analysis to focus on alveolar breath, in essence the breath exhales from the base of the lungs, as a means for minimising the contamination of samples and for their standardisation. A means for its identification is through the monitoring of the expired CO2. A new approach to CO2 sensing using LPGs coated with an ionic gel has been developed, with a key feature being the insensitivity of the ionic gel-coated LPG to humidity. This has resulted in a successfully completed PhD project. A compact, battery powered instrument incorporating light source, spectrometer and data acquisition and processing systems was designed and constructed with a built-in touch screen. Data capture and processing is performed using a Raspberry Pi. The software interface developed facilitated easy operation and a clear display indicating the changes in the LPG transmission spectrum. This is significant, as the majority of LPG sensor research is carried out at telecommunications wavelengths, using expensive and often complex broadband light sources that cover the near infrared spectrum from 1300nm to 1700 nm coupled with an optical spectrum analyser and generally confined to the laboratory. The system developed here offers a route to allowing this sensing platform to find more practical application.
The use of 3D printing technology initiated under this funding stimulated interest in other, related applications, culminating in a demonstration of a 3D-printed microfluidic lab on a disk platform that could be used to separate plasma from whole blood when spun in optical disk drive. This was the subject of a successful PhD. During the program, the deposition of a number of other coating materials, including metal organic frameworks, bacteriorhodopsin, titanium, calixarene, gold shell nanoparticles, graphene and antibodies was explored for potential application in environmental and water quality monitoring and for specific detection of bacteria.
Exploitation Route The work to date will be of benefit to researchers looking into packaging solutions for optical fibre sensors.
The improvements in the fibre sensor fabrication process will be of considerable interest to the field and we have published our work in this area.
The long period grating sensor interrogator developed here is the first portable system, to our knowledge, offering a route to allowing this sensing platform to find more practical application.
Sectors Agriculture, Food and Drink,Chemicals,Healthcare

 
Title Data from "Long period grating based toluene sensor for use with water contamination" 
Description Data associated with a publication describing the development of a fibre optic based toluene sensor. http://dx.doi.org/10.1016/j.snb.2014.06.121 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact none as yet 
 
Title Data from "Multi-parameter measurements using optical fibre long period gratings for indoor air quality monitoring" 
Description measurement of temperature, humidity and VOC concentration using multiplexed optical fibre long period grating sensors Data underlying the results presented and discussed in: Multi-parameter measurements using optical fibre long period gratings for indoor air quality monitoring Jiri Hromadk, Sergiy Korposh, Matthew C. Partridge, Stephen W. James, Frank Davis, Derrick Crump, Ralph P. Tatam Published in Sensors and Actuators B 2017. (http://dx.doi.org/10.1016/j.snb.2016.12.050) 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact none as yet 
URL https://doi.org/10.17862/cranfield.rd.4288373.v1
 
Title Overwrite LPG spectra 
Description Transmission spectra recorded during the formation of an LPG using the overwrite fabrication method, reported in https://doi.org/10.1364/OE.24.022345 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact non as yet 
 
Title ammonia sensing using lossy mode resonances on a tapered fobre 
Description data underlying a publication describing the development of an ammonia sensor exploiting functional coatings deposited onto a tapered optical fibre - paper available at http://dx.doi.org/10.1016/j.snb.2016.11.092 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact first report fof the use of lossy mode resonances for sensing of ammonia with sub ppm limit of detection 
URL https://doi.org/10.17862/cranfield.rd.4055010.v1
 
Title formation of cascaded LPGs using the overwrite method 
Description Transmission spectra recorded during the formation of a cascaded LPG pair using the overwrite fabrication method. the work was presented in http://dx.doi.org/10.1364/OE.24.022345 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact non as yet 
 
Title indoor air quality study 
Description the data that underlies a report on a study of the use of optical fibre sensors for monitoring indoor air quality. The paper can be accessed at http://dx.doi.org/10.1016/j.snb.2016.12.050 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact first report of the use of a multiplexed array optical fibre long period gratings to monitor temperature, humidity and VOCs 
 
Title spectra of LPGS witth periods 166 microns to 177 microns 
Description the data shows, for the first time experimentally, the dependence of the transmission spectrum of an optical fibre long period grating upon the period of the grating. Data was presented in a paper available at : 10.1109/ICSENS.2016.7808441 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact none as yet 
 
Title spectral evolution during coating 
Description the evolution of the transmission spectrum of an optical fibre long period grating during the deposition of a Langmuir Blodgett layer of calix[4]resorcinarene C11. Underlies a research paper available at http://dx.doi.org/10.1016/j.snb.2014.06.121 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact none 
 
Title A portable interrogator for optical fibre long period grating (LPG) sensors. 
Description A highly portable interrogator for optical fibre long period grating (LPG) sensors. The system employs a compact broadband light source and CCD spectrometer, using a Raspberry Pi to acquire, process and log the data, with a touch screen interface that allows control of the instrument and visualisation of the evolution of the transmission spectrum of the LPG. The system is suited to use with LPGs fabricated in optical fibres with cut-off wavelength of order 600 nm, such that, within the spectral window of silicon CCD detectors, the LPG transmission spectrum contains spectral features that are highly sensitive to environmental perturbations. The design of the system and the software will be made available on the Universities data repository. 
Type Of Technology Systems, Materials & Instrumental Engineering 
Year Produced 2016 
Impact None as yet.