It is important to clarify that at 8 fractionated additions of TEOS between 0.1 to 0.3 mmol of NH 4 OH and 0.25 and 0.75 mmol of TEOS, it is predicted that no coating of the SPION core would occur. This is a limitation of the experimental design model, where the resulting models are often less reliable at the extremities of the experimental domain. In practice, these conditions are likely to produce SPION embedded in a silica matrix, similar to those formed at treatments 111, 112 and 113, for reasons discussed previously.