Research Documented Retrograde Flow

Although the concept of retrograde flow may seem hard to believe, the phenomenon has been independently validated by various researchers from the USA, Netherlands, Russia, and England over the past 50 years. The phenomenon has been described in scientific literature with terms such as reflux, back flow and back leak.

Retrograde flow was initially observed in the first multi-use nozzle jet injector, the Press-O-Jet, during the 1950s. Elisberg, McCown and Smadel (1956) reported, the “backflow of inoculum mixed with the subject’s bodily fluids,” however it was their belief that “the precautionary quick withdrawal of the jet injection syringe immediately after the inoculation is finished prevents contamination of the nozzle with agents which might transmit a blood-borne infection.” Contrary to Elisberg, McCown and Smadel’s belief, subsequent research has shown prompt removal of the jet gun failed to stop cross-contamination within the half second it took to administer the vaccination.

Robert Hingson acknowledged a “back leak” of fluid within his 1963 paper in the Military Medical Journal. Hingson wrote, “Because of the need for readjustment by the tissues which so suddenly receive the 1 cc. injection, we recommend keeping the injector nozzle compressed tightly against the injected site for one second after injecting, to minimize back leak” (Hingson, Davis & Rosen, 1963). Hingson’s belief was the jet injector would act as a barrier, stopping the back flow of fluid, and give time for the fluid to absorb into the surrounding tissue. However, Hingson failed to test if the “back leak” would breach the nozzle orifice and contaminate the inside of the jet injector.

A researcher for the World Health Organization wrote about “reflux” when using Ped-O-Jets in his 1971 report on Yellow Fever vaccinations. Dr. Y. Robin noted,

The quantity of liquid expelled can be regulated from 0.1 to 1 ml. Owing to the reflux caused by the elasticity of the skin, in order to inject 0.10 ml it is necessary to eject 0.15 ml (Dull, 1968). This ejected volume was measured by weighing on a precision balance. The volume did not vary, throughout the operations, by more than +/- 5.3%, which is no greater than in the case of injection by syringe (WHO, 1971).

Here, Robin and Dull were noting the loss of vaccine during hole formation which occurred at the beginning of the jet injection. The use of the word “reflux,” meaning the backwards flow of a liquid, demonstrates that Robin and Dull both knew the vaccine flowed backwards. Granted these researchers did not know of the full effect of retrograde flow; however, Robin and Dull did state due to the elasticity of the skin the fluid was not absorbed within the body but moved backwards and out of the body.

Dutch researchers observed retrograde flow during the 1980s. Brink and colleagues (1985) found cross-contamination of a highly infectious virus occurred within their study on mice despite the lack of visual bleeding at the injection site. The researcher’s hypothesized, “Probably the enormous tissue pressure caused a splashback of the injected fluid. This retrograde stream could be responsible for the transport of virus particles.” The researchers further stated investigations should be conducted to see if this phenomenon occurs in humans.

Russian researchers, Evstigneev and Lukin, noted retrograde flow within their investigations during the 1990s. The researchers wrote, “infection is possible because of retrograde flow of vaccine preparation which just has mixed with tissue liquid of a previous patient or taking into account a continuous contact of an injector head with patient’s skin during injection” (Evstigneev & Lukin, 1994).

Researchers from Kalamazoo College investigated the potential for cross-contamination with the Syrijet, a multi-use nozzle jet injector made from the same manufacturer as the Ped-O-Jet. In assessing the transference of microbial pathogens during the injection process, Suria and colleages (1999) found, “the degree of backflow and resulting contamination increased with increasing ejection volume setting, from lowest (0.06 cm3) to highest (0.30 cm3).” Suria observed the greater the volume the greater degree of internal contamination from retrograde flow. Suria also noted swabbing the nozzle of the jet injector did not remove internal contamination.

Joy Baxter and Samir Mitragotri both described the mechanical workings of jet injection in their 2006 paper. Baxter, a researcher for Unilever Research and Development, and Mitragotri, a chemical engineer at Harvard University, wrote, “Backflow of the jet is observed during hole formation if the volumetric rate of hole formation in the skin is smaller than the volumetric flow rate of the jet liquid into the skin” (Baxter & Mitragotri, 2006).

In October of 1998, the WHO conducted a simulated field trial to assess the degree of blood transmission via Ped-O-Jet injectors. Swabbing the nozzle of the Ped-O-Jet did not eliminate but only slightly reduced the degree of contamination. This finding indicates contamination was present inside the injector’s internal fluid pathway, beyond the reach of swabbing the nozzle, due to retrograde flow (Hoffman et al., unpublished).

Hoffman also found retrograde flow within his laboratory investigations of four different jet injectors. In fact, the researcher found retrograde flow was a natural phenomenon within the jet injection process and referred to it as “ballistic contamination” (Voelker, 1999). Hoffman thoroughly explained the process within his paper.

…some of the liquid injected form[ed] a pocket below the injection site. This will be under maximum pressure towards the end of the injection process, before sufficient dispersion into surrounding tissues has occurred to release pressure. This will coincide with a lessening of pressure from the injector. When the pressure from the injector is exceeded by the back-pressure from the tissue pocket, backflow through the pathway in the skin created by the injector could occur. This liquid will contain blood from the destruction of small blood vessels during the injection process and can have different pathways after it has emerged from the skin according to the type of injector. Injectors that have direct skin contact will form a continuous fluid pathway between the skin and injector. As the outward pressure from the injector dies away at the end of an injection, back-pressure from the fluid in the tissue pocket will cause blackflow out of the skin to inside the injector’s fluid pathway (Hoffman et al., 2001).

The Program for Appropriate Technology in Health (PATH) assessed the degree of contamination with jet injectors during the mid-1990s. The tests sought to detect contamination in three areas: 1) On the surface of the skin that was injected, 2) upon the surfaces of the jet injector that had contact with skin, and 3) in the ejectates, or rather the next dose fired. The tests “showed systematic contamination of both the ejectate and the internal fluid pathway” (WHO, 1997). Contamination of the internal fluid pathway could only have occurred due to either fluid suck-back or retrograde flow.

PATH redeveloped jet injectors to avoid the risk of cross-contamination by implementing a single-use protector cap to shield the jet injector from splash-back. However, as safety testing showed, the protector cap was not infallible. Kelly and colleagues (2008) found the Hepatitis B virus cross-contaminated through the protector cap and into the next dosage to be fired. Cross-contamination could only have occurred by the phenomenon of retrograde flow.


  • (Baxter & Mitragotri, 2006) Baxter J, Mitragotri S. Needle-free liquid jet injections: mechanisms and applications. Expert Rev Med Devices Sep 2006;3(5):565-74.
  • (Brink et al., 1985) Brink PRG, van Loon AM, Trommelen JCM, Gribnau FWJ, Smale-Novakova IRO. Virus transmission by subcutaneous jet injection. J Med Microbiol. December 1985; 20(3): 393-397.
  • (Elisberg, McCown, & Smadel, 1956) Elisberg BL, McCown JM, Smadel JE. Vaccination against smallpox. Jet injection of chorio-allantoic membrane vaccine. J Immunol 1956;77(5):340-351.
  • (Evstigneev & Lukin, 1994) Evstigneev VI, Lukin EP. The safety of the jet (needle-free) injection. Military Medical Journal (Russia) Jul 1994; (7):38-39, 79.
  • (Hingson, Davis, & Rosen, 1963) Hingson RA, Davis HS, Rosen M. The historical development of jet injection and envisioned uses in mass immunization and mass therapy based upon two decades’ experience. Military Medicine 128:516–524, 1963.
  • (Hoffman et al., unpublished) Hoffman PN, Abuknesha RA, Andrews NJ, Brito GS, Carrasco P, Weckx LY, Moia LJMP, Silva AEB, Lloyd J. A field trial of jet injector safety in Brazil. (unpublished).
  • (Hoffman et al., 2001) Hoffman PN, Abuknesha RA, Andrews NJ, Samuel D, Lloyd JS. A model to assess the infection potential of jet injectors used in mass immunisation. Vaccine. 16 July 2001;19(28-29):4020-4027.
  • (Kelly et al., 2008) Kelly K, Loskutov A, Zehrung D, Puaa K, LaBarre P, Muller N, Guiqiang W, Ding H, Hu D, Blackwelder WC. Preventing contamination between injections with multi-use nozzle needle-free injectors: a safety trial. Vaccine (2008) 26, 1344-1352.
  • (Suria et al., 1999) Suria H, Van Enk R, Gordon R, Mattano LA Jr. Risk of cross-patient infection with clinical use of a needleless injector device. Am J Infect Control. 1999 Oct; 27(5):444-7).
  • (Voelker, 1999) Voelker R. Eradication Efforts Need Needle-Free Delivery. JAMA May 26, 1999;281(20):1879-1881.
  • (WHO, 1971) Robin, Y. Yellow Fever Vaccination, Alone or In Association, Using 17 D Vaccine Administered Intradermally. Geneva: World Health Organization, Expert Committee on Yellow Fever, document 2 March 1971; 1-5.
  • (WHO, 1997) World Health Organization. Steering group on the development of jet injection, Geneva, 18-19 March 1997. Geneva: World Health Organization, Global Programme on Vaccines and Immunizations, document, 1997;1-37.

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