It would depend how the question was phrased. It would be wrong for the prosecution to suggest, as a general principle, that the jury must be sure of a defendant's innocence in order to acquit. The standard is that they must be sure* of the defendant's guilt in order to convict. But it would also be wrong for the defence to suggest that demolition of some individual piece of prosecution evidence meant that the jury could not be sure of a defendant's guilt unless that actually was the case (i.e. unless it was, by itself, sufficient to rule out the possibility of proving the defendant's guilt).
As a concrete example, consider the insulin evidence in the case of Child F or Child L. If the defence had established that this neither proved Letby guilty, nor proved her innocent, then the jury could still convict because they might feel that the rest of the prosecution argument was nonetheless sufficient to make them sure of her guilt. If, on the other hand, the defence showed that this individual piece of evidence proved her innocence then they would have had no option but to find her innocent, and the judge might direct them to do so.
So, when considering evidence as a whole, the only question in a jury's mind should be whether they are sure of the defendant's guilt. But when considering individual pieces of evidence, they (and to a certain extent the judge as well, because he/she has the option of directing an acquittal) must consider at least three possibilities. This piece of evidence might prove innocence, in which case its game over for the prosecution, or it might prove guilt, in which case it's game over for the defence, or it might be just part of a set of evidence that has to be considered in the round.
The prosecution summing up in Letby it has a "Never mind the quality, feel the width," flavour to it. The prosecution accept that the evidence is circumstantial (in some cases using the word "circumstantial" in a weirdly loving way) and that no individual piece of evidence proves Letby's guilt. But they argue that collectively, this circumstantial evidence should make the jury sure of her guilt. This is, logically, a bit tendentious. Legally however it is a perfectly acceptable line of argument, unless, somewhere in this mass of evidence, there is something that proves innocence, in which case the Jenga tower built up by the prosecution falls down.
* I am not sure what happens in the US these days, but in the UK, judges are now instructed to use the phrase "sure" rather than "beyond reasonable doubt" when describing the standard of proof required.