Development of spectral domain optical coherence tomography for pharmaceutical and medical application

Spectral-domain optical coherence tomography (SD-OCT) is a type of non-destructive imaging technique that is capable of resolving the inner structure of a sample with micrometre spatial resolution. SD-OCT is based on low coherence interferometry. It utilises a spectrometer to grab the spectral interferogram between the back reflected/scattered light from a reference mirror and a sample. The depth profile, which carries the sample inner structure information, is then generated by a data interpolation and Fourier Transform (FT). Functional coating of solid oral dosage forms optimises the release profile of active pharmaceutical ingredient (API) and results in a desirable API absorption rate in the human body. Therefore, the characterisation of the coating structure is significant in the pharmaceutical industry. In order to resolve the coating structure of film coated pharmaceutical tablets off-line, a general-purpose free space SD-OCT system is firstly implemented. The axial and lateral resolution of the SD-OCT system is 2.6 µm and 16 µm respectively, and it requires a mechanical lateral scan by rotating a galvo mirror to generate a cross-sectional image. The coating thickness quantified by the mean depth profile is in the range of 30 µm to 220 µm. The diameter of a pharmaceutical pellet is typically at the sub-millimetre scale, which leads to stronger scattering compared with a tablet with typical dimensions larger than 5 mm. The galvo mirror based scanning system sweeps the sample beam on the sample to perform the mechanical lateral scan. It increases the incident angle of the sample beam and collects less backscattered sample beam at the side of the pellet sample. To address this issue, a translation stage replaces the galvo mirror to move the pellet sample. The sample beam always stays at the centre of the lens, thus more backscattered light from a sample can be collected. Moreover, to realise the online measurement, a fibre based SD-OCT system with a flexible probe head was implemented to reduce the system dimensions. The fibre based SD-OCT system has the advantage of compactness and portability. The fibre sensor head can be easily integrated into a pharmaceutical coater. In the well-established clinical application of OCT, one has to minimise the motion artefact associated with the movement of human eyes to assess the corneal structure in vivo. One solution to solve this problem is to grab multiple A-scans simultaneously. A single-shot SD-OCT system with a two-dimensional detector array is built to grab multiple spectral interferograms in parallel. The single-shot SD-OCT system is successfully applied to evaluate the corneal thickness under different pressures. Furthermore, we demonstrated for the first time that change in corneal thickness variance down to nanometre resolution can be quantified using the phase information of the complex depth profile. We are in the process of applying for a patent to protect the developed technology. Built on the success of this work, a major project has also been funded (NIHR i4i scheme) to develop this technology further for medical applications. The algebraic reconstruction technique (ART) based optical coherence tomography (OCT) allows reconstruction of the depth profile of a sample directly in the wavelength domain using the sparse approximation method. We propose a fast sparse approximation algorithm which combines the orthogonal matching pursuit (OMP) method with a spectrum split approach for the reconstruction of the depth profile of a sample. As a demonstration, we applied ART-OCT to study pharmaceutical tablet coatings in a thickness range of 30-183 µm. We showed that the proposed reconstruction method has low computational complexity which leads to a much faster reconstruction speed as compared with the more widely used l1-optimisation method. Furthermore, the novel combination of the OMP method with the spectrum split approach has also led to over 3.7dB improvement in signal to noise ratio (SNR) of the reconstructed cross-sectional image of the coated tablets. This work has been presented at 2014 UCL-Duke Workshop on Sensing and Analysis of High-Dimensional Data, and a paper based on this work has been drafted and will be submitted for journal publication