**Core Concept**
The presence of spherocytes in a peripheral blood smear is indicative of a disorder affecting the red blood cell membrane, specifically hereditary spherocytosis or autoimmune hemolytic anemia. Spherocytes are characterized by their spherical shape, which results from the loss of membrane surface area.

**Why the Correct Answer is Right**
The most relevant investigation to diagnose spherocytosis is the osmotic fragility test. This test measures the ability of red blood cells to withstand osmotic stress, which is compromised in spherocytes due to their reduced surface area-to-volume ratio. In the osmotic fragility test, red blood cells are suspended in hypotonic saline solutions of varying concentrations, and the percentage of hemolysis is measured. Spherocytes exhibit increased hemolysis in hypotonic solutions compared to normal red blood cells.

**Why Each Wrong Option is Incorrect**
**Option A:** Reticulocyte count may be elevated in various types of hemolytic anemia, including spherocytosis, but it is not specific for diagnosing spherocytosis.

**Option B:** Coombs test is used to diagnose autoimmune hemolytic anemia, which can also present with spherocytes, but it does not specifically diagnose spherocytosis.

**Option C:** Bone marrow examination may reveal erythroid hyperplasia in various types of anemia, including spherocytosis, but it is not the most relevant investigation for diagnosing spherocytosis.

**Clinical Pearl / High-Yield Fact**
The osmotic fragility test is a classic diagnostic tool for hereditary spherocytosis, but it may be abnormal in other conditions as well. A more specific test for diagnosing hereditary spherocytosis is the flow cytometric analysis of red blood cell membrane proteins.

**Correct Answer:** C.