THE CABINET

The lyophilizer

The freeze-drying device constructed from spare parts

Technical file

Type of innovation: Device

Scope: Bioengineering

Innovation leader: Grifols i Lucas, Víctor

Year: 1943

Period: 1909-1971

Geographical scope: Spain

Economical impact: High

Level of innovation: Disruptive

Patent: Yes

Interdisciplinary connections: Light bulb manufacturers Refrigerators

Brothers Josep Antoni and Víctor Grifols i Lucas had been investigating the process of lyophilization and its application to human plasma since 1935. They introduced the patented procedure to Spain in 1943, and Víctor was in charge of developing a lyophilizer to capitalize on the investment.

Overcoming scarcity with ingenuity

Due to the scarcity of materials during the post-war period in Spain, the first prototype designed by Víctor Grifols i Lucas was made using second-hand components, such as a vacuum machine from a light bulb factory. But to verify that it worked, it was necessary to use a very precise vacuum meter, a device that did not exist in Spain at the time. Víctor commissioned one from a local company, providing all the necessary calculations to manufacture the instrument.

The next step was to test the pumping mechanism. The first attempts were a failure, and did not reach the minimum vacuum necessary. They wasted a lot of time trying to adjust the device, until in the end they discovered the cause: the oil the vacuum pump had to be submerged in so as to prevent air from entering through tiny holes, contained volatile compounds. These chemicals were seeping into the device and preventing a vacuum from forming.

“The process proved extremely popular, and years later Nestlé would come to Grifols to learn the technique that was being used with plasma and apply it to the manufacture of instant coffee.”

From hot oil to dry ice

The solution was to heat the oil over a primus stove to evaporate the offending compounds. Víctor Grifols spent the night with an extinguisher by his side trying not to fall asleep and risk setting the house on fire. At six o'clock in the morning he turned off the stove and let the oil rest. Once it was cold, he started up the pump–which now created a vacuum.

The final part of the puzzle was refrigeration. It had to be moisture-free, so dry ice was used, but later a refrigeration compressor proved more practical. Ideally, a temperature of minus 70º Celsius was needed for the process. But the materials available at the time would only let them achieve minus 40º Celsius. They overcame the problem by slowing the entire process down—and finally it worked.

Patience and innovation are rewarded

After overcoming all the difficulties that arose when building the lyophilizer, Laboratorios Grifols became the first to lyophilize plasma in Spain. The lyophilized plasma could be stored at room temperature for five years, the shelf-life established by the American pharmacopoeia. That longevity was a vast improvement on just 21 days for fresh liquid plasma, and illustrates just how important the production of the Grifols lyophilizer was. The process proved extremely popular, and years later Nestlé would come to Grifols to learn the technique that was being used with plasma and apply it to the manufacture of instant coffee.

In order to sell it to hospitals throughout Spain, Grifols established an embryonic sales network, whose first representative was Juan Taberner, in Alicante.

Bibliography

  • Grifols-Roig, J.A. (1943). Un procedimiento para desecar plasmas, sueros, líquidos biológicos en general y organismos inferiores conservando al máximo sus propiedades originales. Patente española de introducción, no. 161.700. Madrid: Oficina Española de Patentes.
  • Laboratorios Grifols. (1944). Plasma humano desecado en estado liófilo. Hemoderivados [Sales brochure]. Barcelona: Laboratorios Grifols, S.A.
  • Robinson, G.C. (1946). American Red Cross blood donor service during World War II; its organization and operation. Washington: American National Red Cross.
  • Greaves, R.I.N. (1947). The preservation of proteins by drying, with special reference to the production of dried human serum and plasma for transfusion. The Journal of the American Medical Association, 134(14), 1207-1209.
  • Grifols-Lucas, V. [ca. 1950]. Primeros registros de plasma liofilizado. [Unpublished manuscript]. Barcelona: Laboratorios Grifols, S.A.
  • Podolsky, M.V., & Karlova, N.G., & Rozenberg, G.Y. (1967). Improved method of lypohilic of plasma stabilized with glucose. Probl Gematol Pereliv Krovi, 12(4), 27-32.
  • Schneider, W.H. (2003). Blood transfusion between the wars. Journal of the History of Medicine and Allied Sciences, 58(2), 187-224.
  • Grifols-Lucas, V. (2009). Amb un suro i un cordill. Vivències d'un empresari de postguerra. Barcelona: Grupo Grifols, S.A.
  • Schmidt, P. J. (2012). The plasma wars: a history. Transfusion, 52, 2-4.
  • Avellà, R., & Miquel, B. (Eds.). (2015). Cuando un sueño se cumple. Crónica ilustrada de 75 años de Grifols. Barcelona: Grupo Grifols, S.A.