Aerobic catabolism of S. cerevisiae (cell respiration) is a rapid, cost-effective, and reproducible toxicological endpoint of the whole cells biosensor. To increase the signal intensity, a protocol for the immobilization and modification of the yeast cells is described. In particular, the enzymatic treatment of the immobilized yeast cells allows removing the cell wall and obtaining structurally modified cells namely spheroplasts. Both immobilization and exposure of sensitive cells like spheroplasts confirmed to improve the method’s sensitivity vs. the chemicals. The present paper reports the test of different chemicals (including Mercury and wood preservative like Tanalith) present in consumer products, performed both by sensor with intact and modified whole cells.