Founders of bionanotechnology?

In a 2009 JACS editorial (10.1021/ja9038104), Thomas E Mallouk and Peidong Yang wrote

Although the use of colloidal particles of metals and semiconductors as pigments dates back many centuries, and although the recipe for stable 6 nm diameter particles of gold (“Ruby gold”) was famously devised by Faraday in 1857,[1] the unique properties of nanomaterials and their promise for applications in biochemistry, cell biology, and medicine have only recently been appreciated. Prior to the 1990s, the principal role of inorganic colloids in biological research was as high-contrast stains for electron microscopy.[2] A paradigm shift occurred in 1996, when Mirkin, Alivisatos, and co-workers coupled metal nanoparticles to DNA.[3] Their experiments demonstrated not only that DNA could be used for the organization of nanostructures, as had been suggested in earlier experiments by Seeman,[4] but also that nanoparticles were highly sensitive spectroscopic reporters for the base-pairing of DNA

This is a commonly held view and there is no doubt that the 1996 paper is an important milestone.

Yet, beyond electron microscopy, gold nanoparticles had been introduced as a diagnostic tool based on a color change 84 years before Mirkin, Alivisatos and co-workers paper. In 1912, Carl Friedrich August Lange introduced gold nanoparticles to detect diseases [1]. Writing a few years later in the Journal of Experimental Pathology [2], John Cruickshank, MD, writes:

It occurred to Lange to examine syphilitic and normal sera by this method, and later to apply the reaction to spinal fluids, as the amount of globulin and albumen was known to vary in different pathological conditions of the central nervous system. Lange found, however, that certain spinal fluids, in addition to exhibiting protective effect on gold colloid, had also unexpected precipitating properties. The spinal fluids of cases of dementia paralytica in particular showed this precipitating property, and as a result of the examination of a series of cases Lange recommended the test for the diagnosis of this disease.


For several decades, the Lange test based on gold nanoparticle color change was used in clinics as reported in numerous papers. It also motivated the synthesis of suitable nanoparticles, e.g. “The Preparation and Standardization of Colloidal Gold for the Lange Test”  in 1931 by Jocelyn Patterson.

[1] Lange, C. Die Ausflockung kolloidalen Groldes durch Cerebrospinalflussigkeit bei luetischen Affecktionen des Zentraluerxensystem,^’ Zeitschr. f. Chemotherap., 1912, 1, 44

[2] Cruickshank, J. Br J Exp Pathol. Apr 1920; 1(2): 71–88

[3] Br J Exp Pathol. Jun 1931; 12(3): 143–146. PMCID: PMC2048186




  1. Can you put links to the papers in the reference list – would help the community to access what might be the founding papers of the field. If any of the papers are not accessible (aka you have to pay to access) it might be good to pressure the publishers, something which would be more effective as a community effort.


  2. Mirkin hypes himself a lot. Talk to some of his students or post-docs. He ridiculed the nanopen idea and then took credit for it, when it was a microscopist postdoc who had recognized the importance of the phenomenon. He’s also into all this nano building stuff hype, when he doesn’t even do lithography. Nor does he do fundamental colloid science or even very strong chemistry. And then just read his papers…just the wording he uses. Hype science.

    Doesn’t surprise me that he does not know the history of colloid fundamentals. He’s an ego scientist. A grant hustler. Not a thinker.


    1. From the second paper cited, it appears that by 1920, already hundreds of patients had their samples analysed with this test, yet I am not aware of any of the thousands of papers published since 1996 based on color change for sensing citing this early work from 1912 onward.
      My post was not meant as a criticism of Mirkin, or of any particular individual for that matter, more a case of collective amnesia, probably due to the fact that the test stopped being used for several decades before nanoparticles for sensing became a hot topic again.


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