PIPES is a member of the ethanesulfonic acid buffer series, first introduced by Good et al., developed to meet certain criteria: midrange pKa, maximum water solubility and minimum solubility in all other solvents, minimal salt effects, minimal change in pKa with temperature, chemically and enzymatically stable, minimal absorption in visible or UV spectral range and easily synthesized. Since its pKa at 37 °C is near physiological pH, PIPES has applications in cell culture work.

Glutaraldehyde fixation of plant and animal tissue samples can cause loss of lipid, leading to apparent morphological changes. Lipid loss and artifacts were minimized when PIPES was used to buffer the glutaraldehyde fixative.^,
Alkaline phosphatase activity is lost selectively from certain rat hepatocyte organelles when fixed for ultracytochemistry with cacodylate-buffered glutaraldehyde. When PIPES was used as buffer, retention of activity was 60% greater.
Fixation of fungal zoospores for fluorescence microscopy and electron microscopy was optimal with a combination of glutaraldehyde and formaldehyde in PIPES buffer.

Sigma-Aldrich offers BioPerformance Certified cell culture-tested PIPES (Product No. P1851) as well as several different salts for convenience in buffer preparation, and PIPES BioXtra (Product No. P8203) which is tested for the presence of trace metals.

Buffers can be prepared by adding a solution of base to PIPES free acid to titrate to the appropriate pH, or by mixing equimolar solutions of the monosodium salt and the disodium salt to titrate to the appropriate pH.