The Science and Technology Facilities Council

United Kingdom Research and Innovation

Agilent Technologies Lda UK Limited

Pavel Matousek

Anthony William Parker

Nicholas Stone

Benjamin Gardner

Kay Sowoidnich

Michael Towrie

Eva Charlotte Eliasson

Julia Griffen

Andrew Owen

Lee Dowden

Methods and apparatus () for Raman spectral analysis of a sample (), such as a pharmaceutical dosage form, are disclosed. Delivery optics () are used to deliver probe light to a delivery region () on the sample, and collection optics () are used to collect, from a collection region () on the sample spaced from the delivery region, the probe light following scattering through the sample. Each of a plurality of target Raman spectral features are measured in the collected light, and a spectral distortion of the collected light arising during scattering through the sample is determined. A property of the sample is then quantified using the target Raman spectral features in combination with the determined spectral distortion, such that the quantified property is compensated for the spectral distortion.

Raman analysis of pharmaceutical dosage forms

We disclose methods and apparatus for measuring pH in a sub-surface volume of a diffusely scattering sample. Probe light is directed to an entry region on the sample surface, and collected from a collection region on the sample surface following diffuse scattering within the sample. The collection region is spatially offset from the entry region, so that when one or more Raman spectral features are detected in the collected probe light, a pH of the sub-surface volume can be determined from the spectral features.

Detection of pH

There are disclosed methods and apparatus () for measuring Raman spectral features () of a sample (), from which background light of variable intensity is also received, for example due to the incidence of ambient light () or due to variable fluorescence. Detection pixels () and storage pixels () are defined on a CCD device (). Laser probe light () is directed to the sample. In a repeated cycle of first and second intervals, in each first interval background light is received at detection pixels, and in each second interval both background light and scattered laser probe light is received at the detection pixels. The accumulated signal from each of the first and second intervals is retained in the storage pixels during the second and first intervals respectively. In other aspects laser probe light is directed to the sample during both of the first and second intervals, but has a different wavelength in each interval.

Raman spectrometer

The disclosure relates to a clinical thermometer for non-invasive measurement of sub-cutaneous temperature of tissue of a human or animal subject. Probe light is collected from a collection region spatially offset from an entry region on a visible surface of the subject, following scattering within the tissue, and a temperature of the tissue is determined from Raman spectral features in the collected light.

Clinical thermometer

The invention provides a technique for increasing the illumination intensity of probe light in a diffusely scattering sample without increasing the power of the probe beam. Generally, an optical filter is used which permits a collimated probe beam of light to pass through to the sample, but which reflects back towards the sample much of the backscattered scattered probe light emerging at a wider range of angles. In particular embodiments a collimated laser beam is delivered to the sample through a multi-layer dielectric filter covering a portion of the sample. The filter is transmissive to the laser light at normal incidence, but reflective at shallower angles of incidence characteristic of the backscattered light.

Illumination of diffusely scattering media

Non invasive in-vivo measurement of composition of a tissue within a part of a human or animal subject is carried out by detecting a Raman spectral characteristic in light scattered through the part using a transmission, rather than a backscattering geometry. The technique is applied to the detection of calcifications in human breast tissues.

Raman analysis of tissue and/or calcifications

Methods and apparatus for screening the unknown contents of containers using Raman spectroscopy are disclosed, especially for security screening applications such as in airports. A probe light beam is directed through the wall of a container to a sample region within the container contents. Light scattered out of the beam within the sample region is collected along a path which passes through a separate part of the container wall, for Raman spectral analysis.

Raman detection of container contents

Apparatus and methods for determining, in-vivo, characteristics of sub-surface tissues or fluids in the human or animal body are disclosed. Incident radiation is supplied at one or more entry regions on a surface, and light is collected from one or more collection regions spaced from the entry regions. Raman features are detected in the collected light and depth related information derived therefrom.

Raman spectral analysis of sub-surface tissues and fluids

Apparatus and methods for detecting Raman spectral features non destructively from sub-surface regions of a diffusely scattering sample are disclosed. Incident radiation is supplied at one or more sample surface entry regions, and light is collected from one or more collection regions spaced from the entry regions. Raman features are detected in the collected light, and depth information is derived according to the entry-collection spacings.

Apparatus for depth-selective Raman spectroscopy

Properties of turbid or scattering samples are determined using Raman spectroscopy with probe light delivered to and subsequently collected from the sample using a transmission geometry. The technique may be applied to pharmaceutical products such as tablets, diagnostic tests such as lateral flow diagnostic strips, and elsewhere.

Raman analysis

Method and apparatus for screening objects using Raman scattering methods to detect the presence of predefined substances or classes of substances. The predefined substances may be hazardous, toxic, or explosive. Radiation is supplied to an incident region of an object. Scattered light is collected from a collection region on the surface of the object spaced from the incident region. The characteristics of the scattered light include Raman features related to the predefined substances. The Raman features allow the presence, or not, of the predefined substances to be determined.

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Oxfordshire, United Kingdom

Pavel Matousek