Nikolay Bulanov
Sechenov First Moscow State Medical University

In 1886, Max Jaffe (1841 - 1911), a German physician and chemist, observed that creatinine produced an intensive red color in alkaline picrate solution and detected needle-formed crystals under the microscope which he reported in his landmark paper (1).

However, the quantitative analytical method used to assess creatinine concentration was developed in the first decade of the twentieth century by an outstanding Swedish-born American biochemist Otto Folin (1867 – 1934), who called it the “Jaffe method” (2). Even over a century after its introduction into clinical practice, this procedure is still widely used to measure creatinine levels due to its simplicity and low-cost. However, several organic compounds called pseudochromogens (e.g. acetone, glucose) that were first recognized by Jaffe can also react with alkaline picrate and lead to an analytical bias.

In 1957, Alfred Free (1913 – 2000) and his co-authors working at the Ames Corporation published a paper describing a new colorimetric test for urinary protein (3). The first dipstick was a yellow paper strip, impregnated with a citrate buffer and tetrabromphenol blue, which turns green in the presence of protein. Free et al tested their new method obtaining approximately 5000 turbid urine samples from patients and healthy subjects and demonstrated its adequate sensitivity and specificity. Today, urinary dipstick test is one of the most common screening techniques for early detection of kidney diseases.

In 1945, Bowling Barnes, David Richardson, John Berry, and Robert Hood introduced flame photometer to measure the low concentration of sodium and potassium in a solution (4). Flame photometer measures the intensity of emitted light when a metal is introduced into the flame, giving information about the amount of the element present in the sample. This technology allows for cheap and simple measurements of electrolytes in serum and urine.


      Jaffe M. Ueber den Niederschlag welchen Pikrinsäure in normalen Harn erzeugt und über eine neue reaction des Kreatinins. Z Physiol Chem. 1886;10:391–400.
      Shaffer PA. Otto Folin 1867-1934. Washington, DC: National academy of sciences;1952:47–82
      Free AH, Rupe CO, Metzler I. Studies with a new colorimetric test for proteinuria. Clin Chem. 1957;3:716–727.
      Barnes RB, Richardson D, Berry JW, Hood RL. Flame photometry; A rapid analytical procedure. Ind Eng Chem Anal Ed. 1945;17:605-11.

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