Numeric simulation can be used to predict heat transfer during the blanching of leaves and intact plants

Heat treatment is often used during the processing of plant-derived biomass to precipitate host cell proteins (HCPs) and thus simplify the purification of target proteins. Plants uniquely allow this precipitation step to be applied within intact leaves rather than large volumes of cell culture supernatant or extract. However, it can be expensive and time consuming to identify the optimal conditions for HCP removal even when applying statistical experimental designs, such as the design of experiments (DoE) approach. An alternative strategy that additionally yields mechanistic insights is the modeling of heat transfer within solid-state biological specimens, such as whole leaves. Here we present a method for the numeric simulation of heat treatment in tobacco (Nicotiana tabacum) leaves, and N. benthamiana leaves and whole plants, using input parameters such as the heating temperature, heat transfer coefficient, specific heat capacity and thermal conductivity, taking convective and conductive heat transfer into account. Incubation times of 0.5-1.0 min were sufficient to reach thermal equilibrium at typical heat transfer coefficients of 20-100 J s−1 m−2 K−1, and convection rather than conduction was the limiting factor, in agreement with published empirical data. The model can thus form the basis of a quality-by-design approach to remove HCPs by heat precipitation. The limits and benefits of modeling are discussed and we provide examples of potential future applications.