In a mixture of colloidal particles and polymer molecules

the particles may experience an attractive "depletion force" if the size of the polymer molecule is larger than the interparticle separation. This is because individual polymer molecules experience less conformational entropy if they stay between the particles than they escape the inter-particle space

which results in an osmotic pressure imbalance inside and outside the gap and leads to interparticle attraction. This depletion force has been the subject of several studies since the 1980s

but the direct measurement of this force is still experimentally challenging as it requires the detection of energy variations of the order of

k

B

T

and beyond. We present here our results for applying total internal reflection microscopy (TIRM) to directly measure the interaction between a free-moving particle and a flat surface in solutions consisting of small water-soluble organic molecules or polymeric surfactants. Our results indicate that stable nanobubbles (

ca

. 150 nm) exist free in the above aqueous solutions. More importantly

the existence of such nanobubbles induces an attraction between the spherical particle and flat surface. Using TIRM

we are able to directly measure such weak interaction with a range up to 100 nm. Furthermore

we demonstrate that by employing thermo-sensitive microgel particles as a depleting agent

we are able to quantitatively measure and reversibly control

k

B

T

-scale depletion attraction as function of solution pH.