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A resistance-sensing mechanical injector for the precise delivery of liquids to target tissue

Nature Biomedical Engineering volume 3, pages 621–631 (2019)Cite this article

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Abstract

The precision of the delivery of therapeutics to the desired injection site by syringes and hollow needles typically depends on the operator. Here, we introduce a highly sensitive, completely mechanical and cost-effective injector for targeting tissue reliably and precisely. As the operator pushes the syringe plunger, the injector senses the loss-of-resistance on encountering a softer tissue or a cavity, stops advancing the needle and delivers the payload. We demonstrate that the injector can reliably deliver liquids to the suprachoroidal space—a challenging injection site that provides access to the back of the eye—for a wide range of eye sizes, scleral thicknesses and intraocular pressures, and target sites relevant for epidural injections, subcutaneous injections and intraperitoneal access. The design of this simple and effective injector can be adapted for a broad variety of clinical applications.

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Fig. 1: The I2T2 design and its mechanism of action.
Fig. 2: The I2T2 can inject into the SCS to deliver a drug to the back of the eye.
Fig. 3: The I2T2 can inject into the SCS and achieve broad coverage despite anatomical variations.
Fig. 4: Drug injected into the SCS with the I2T2 can reach the inner tissue layers of the retina and choroid through diffusion shortly after injection.
Fig. 5: The I2T2 can be used to deliver microparticles and cells throughout the SCS.
Fig. 6: Potential utility of the I2T2 as a technology for accessing tissues and tissue compartments.

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Data availability

The authors declare that all data supporting the findings of this study are available within the paper and its supplementary information.

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Acknowledgements

Funding for this research was provided by grant no. R01HL095722 to J.M.K. Animal experiments were funded through the Boston-KPro research fund to M.G.A. and A.C. We thank Y. Jung and C. P. Lin for use of the intravital microscope, H. G. Lin and Harvard’s Center for Nanoscale Systems for use of the microCT system, and K. Cormier and the Hope Babette Tang Histology Facility at the Koch Institute at MIT for performing histology sections. We also thank the Schepens Eye Research Institute’s Animal Facility, especially J. Hoadley, M. Ortega and C. Beiler for their help. We appreciate the feedback on performing SCS injections with an I2T2 from D. Vavvas, V. Satitpitakul and K. Suri, from the Massachusetts Eye and Ear Infirmary.

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Author notes

  1. These authors contributed equally: Mohan K. S. Verma, Julien Lamazouade.

Authors and Affiliations

  1. Engineering in Medicine, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Girish D. Chitnis, Mohan K. S. Verma, Julien Lamazouade, Kisuk Yang, Ali Dergham, Peter Anthony Jones, Benjamin E. Mead, Zhixiang Tong, Keir Martyn, Aniruddh Solanki, Natalie Landon-Brace & Jeffrey M. Karp

  2. Harvard−MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, USA

    Girish D. Chitnis, Mohan K. S. Verma, Julien Lamazouade, Kisuk Yang, Ali Dergham, Peter Anthony Jones, Benjamin E. Mead, Zhixiang Tong, Keir Martyn, Aniruddh Solanki, Natalie Landon-Brace & Jeffrey M. Karp

  3. Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA

    Miguel Gonzalez-Andrades & Andrea Cruzat

  4. Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Department of Ophthalmology, Reina Sofia University Hospital and University of Cordoba, Cordoba, Spain

    Miguel Gonzalez-Andrades

  5. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA

    Kisuk Yang & Benjamin E. Mead

  6. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Kisuk Yang, Benjamin E. Mead & Jeffrey M. Karp

  7. Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA

    Kisuk Yang, Benjamin E. Mead & Jeffrey M. Karp

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  1. Girish D. Chitnis
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Contributions

G.D.C. M.K.S.V. and J.M.K. conceptualized and iterated the principle and design of the I2T2. G.D.C., M.K.S.V. and J.L. were responsible for study design, guided by J.M.K. G.D.C. and J.L. developed the analytical model, improved the design and performed detailed experimental studies with focus on ocular applications. G.D.C., M.G.-A., A.C. and J.L. designed and performed the in vivo experiments. B.E.M., A.S., N.L.-B., Z.T., K.M. and K.Y. provided experimental support for the experiments with cell injections in the SCS. G.D.C., M.K.S.V. and A.D. tested the device for applications other than eye. G.D.C. and J.L. were responsible for conceptual drawings and data representation. B.E.M. captured all the photographs under the supervision of G.D.C. and J.L. G.D.C. wrote the manuscript with constructive feedback and editing from J.M.K., J.L., B.E.M. and P.A.J.

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Correspondence to Jeffrey M. Karp.

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Supplementary information

Supplementary Information

Supplementary methods, figures, tables and video captions.

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Supplementary Video 1

Ventricular access through the heart wall by using i2T2 (ex vivo model).

Supplementary Video 2

Accessing the peritoneal cavity through the abdominal wall by using i2T2 (ex vivo model).

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Chitnis, G.D., Verma, M.K.S., Lamazouade, J. et al. A resistance-sensing mechanical injector for the precise delivery of liquids to target tissue. Nat Biomed Eng 3, 621–631 (2019). https://doi.org/10.1038/s41551-019-0350-2

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