A meta-analysis of biological variation in blood-based therapy as a precursor to bio-manufacturing.

Currently cellular therapies, such as hematopoietic stem cell transplantation (HSCT), are produced at a small scale on a case-by-case basis, usually in a clinical or near-clinical setting. Meeting the demand for future cellular therapies will require a robust and scalable manufacturing process that is either designed around or controls the variation associated with biological starting materials. Understanding variation requires both a measure of the allowable variation (that does not negatively affect patient outcome) and the achievable variation (with current technology). The prevalence of HSCT makes it an ideal case study to prepare for more complex biological manufacturing with more challenging regulatory classifications. A systematic meta-analysis of the medical literature surrounding HSCT has been completed of which the key outcomes are the following: (i) the range of transplanted CD34+ cells/kg can be up to six orders of magnitude around the median for allogeneic procedures and four orders of magnitude for autologous procedures, (ii) there is no improvement in variation encountered over a period of 30 years and (iii) as study size increases, the amount of variation encountered also increases. A more detailed, stratified source from a controlled single-site clinical center is required to further define a control strategy for the manufacture of biologics.

Nonperturbing measurements of spatially distributed underwater acoustic fields using a scanning laser Doppler vibrometer.

Localized changes in the density of water induced by the presence of an acoustic field cause perturbations in the localized refractive index. This relationship has given rise to a number of nonperturbing optical metrology techniques for recording measurement parameters from underwater acoustic fields. A method that has been recently developed involves the use of a Laser Doppler Vibrometer (LDV) targeted at a fixed, nonvibrating, plate through an underwater acoustic field. Measurements of the rate of change of optical pathlength along a line section enable the identification of the temporal and frequency characteristics of the acoustic wave front. This approach has been extended through the use of a scanning LDV, which facilitates the measurement of a range of spatially distributed parameters. A mathematical model is presented that relates the distribution of pressure amplitude and phase in a planar wave front with the rate of change of optical pathlength measured by the LDV along a specifically orientated laser line section. Measurements of a 1 MHz acoustic tone burst generated by a focused transducer are described and the results presented. Graphical depictions of the acoustic power and phase distribution recorded by the LDV are shown, together with images representing time history during the acoustic wave propagation.

Sensitivity errors in interferometric deformation metrology.

Interferometric measurement techniques such as holographic interferometry and electronic speckle-pattern interferometry are valuable for measuring the deformation of objects. Conventional theoretical models of deformation measurement assume collimated illumination and telecentric imaging, which are usually only practical for small objects. Large objects often require divergent illumination, for which the models are valid only when the object is planar, and then only in the paraxial region. We present an analysis and discussion of the three-dimensional systematic sensitivity errors for both in-plane and out-of-plane interferometer configurations, where it is shown that the errors can be significant. A dimensionless approach is adopted to make the analysis generic and hence scalable to a system of any size.