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VivoSight Imaging and Measurements for Microneedle Optimization

Visualize micro-channel creation and insertion depth. Monitor the time course of needle degradation or swelling and skin and vascular changes at the insertion site

VivoSight provides unique microneedle (MN) imaging and measurements to optimize:

  • Performance of MN-based drug delivery
  • MN insertion and retention consistency
  • Long-term safety of repeated MN applications
  • Development of standards for MN design, manufacturing and quality control
VivoSight real-time in-vivo imaging of MNs
VivoSight D-OCT image of inserted microneedle array patch with needles and bloodflow
VivoSight image with vascular overlay. Microneedle penetrates 800 μm deep [2]

VivoSight Dx capabilities to advance your MN development include:

  • VivoSight Dx capabilities to advance your MN development include: In-vivo imaging of microneedles in real time
  • Measure microneedle dimensions, penetration depth, dissolution and swelling
  • Measure inflammatory response via vascular changes
  • Understand morphology of device created skin defects
  • Measure kinetics of pore closure and skin recovery
  • Verify reproducibility, consistency of results
Professor Ryan Donnelly - Queens University Belfast smiling and holding model of Microneedle Array Patch

“VivoSight OCT is essential for our microneedle research and for the development of related devices and applications. The ability to visualize polymeric microneedles in-vivo allows for measurement of the exact depth of penetration. Moreover, OCT allows us to monitor swelling and dissolution kinetics of biodegradable needles. It is an indispensable tool to advance and optimize Microneedle Array Patch (MAP) research and product development”. [1, 3]

– Ryan F. Donnelly, PhD, School of Pharmacy, Queen’s University Belfast, UK

In-Vivo Structural Analysis of Microneedle Array Patches (MAPs)

VivoSight pixel resolution of 4.4 μm can identify the details of most microneedle arrays

Ex-vivo VivoSight Dx OCT image of Microneedle patch needles with needle dimensions
Image stacks can contain up to 500 frames, which is sufficient detail to capture the geometries of most MAPs
The patch in this image has a 400 μm thick substrate with MN dimensions of 500 μm long and 300 μm in diameter
Close up of VivoSight OCT image of imperfectly inserted Microneedle Array Patch with varying penetration
Magnified in-vivo view of MAP. Note varying air gap and needle penetration

Polymer MAPs reflect light differently than skin allowing them to be identified in-vivo

MAP measures via OCT:

  • Needle dimensions
  • Needle penetration depth
  • Pore diameter
  • Air gap
  • Substrate thickness
  • Dissolution and swelling behavior
Diagram of Microneedle Array Patch insertion with measurements of pore size air gap and depth of insertion
Close up of VivoSight OCT image of imperfectly inserted Microneedle Array Patch with varying penetration

Relevance of MAP measurements [3]

Needle dissolution and swelling rates

  • Drug delivery optimization
  • Fluid absorption and sampling optimization
  • Substrate or resevoir involvement
Diagram of Microneedle Array Patch insertion before and after.

Drug Delivery:

Swelling of microneedles and high does drug and vaccine delivery through seperate drug-containing layer

Needle penetration depth:

  • Dermal penetration optimization relevant to specific application
Diagram of Microneedle Array Patch insertion with Drug delivery

Fluid Sampling:

Optimized microneedles for extraction of skin interstitial fluid. Opportunity to sample biomarkers and drugs for diagnostics, patient monitoring and wearable sensors

Needle array geometry

  • Verify consistent patch insertion and retention behavior
Diagram of Microneedle Array Patch insertion

Energy Delivery:

Loading of hydrogel-forming Microneedle Array Patches (MAPs) with laser target chromophores (plasmonic gold nanorods) for controlled laser photothermal therapy of non-melanoma skin cancer

Pore size:

  • Skin recovery optimization

VivoSight 6 mm x 6 mm field of view encompasses a large portion of an array

VivoSight image stack can be viewed frame by frame to focus on areas of interest for measurements like consistent penetration depth
VivoSight image stack can be viewed frame by frame to focus on areas of interest for measurements like consistent penetration depth
Magnified image of VivoSight OCT image of a Microneedle showing inserted depth and air gap
Magnified view of selected frame showing:
• Needle penetration of skin
• Size of air gap
• Skin/substrate interface

VivoSight allows you to monitor and measure needle length and insertion depth over time

Chart of needle length & insertion depth
  • Blue (a + b): Total needle length.
    Reduces over 20 minutes as needle changes shape to a blunt cone
  • Orange (b): Needle penetration into the skin. About 75% of the needle penetrated the skin.
  • The air gap between skin and substrate is the difference between the two; it reduces over 20 minutes
Diagram of Microneedle Array Patch insertion with measurements of pore size air gap and depth of insertion

VivoSight allows you to monitor and measure pore size, swelling and dissolution over time

Proportion of needle affected increases linearly with time
Proportion of needle affected increases linearly with time
A sequence of VivoSight OCT images of Microneedle Array Patch inserted into skin showing increasing penetration and needle swelling.
OCT visualizes change of polymer state as it hydrates (turns from grey to black)

References:

1. R.F. Donnelly et al. Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution. Journal of Controlled Release 147 (2010) 333–341

2. S. Sharma, et al., Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring, Sensing and Bio-Sensing Research (2016), http://dx.doi.org/10.1016/j.sbsr.2016.10.004

3. R.F. Donnelly et al. Evaluation of the clinical impact of repeat application of hydrogel-forming microneedle array patches. Drug Delivery and Translational Research (Feb 2020). https://doi.org/10.1007/s13346-020-00727-2

4. E. Kim et al., Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development, EBioMedicine (2020), https://doi.org/10.1016/j.ebiom.2020.102743

5. M. R. Prausnitz, Engineering Microneedle patches for vaccination and drug delivery to skin. Annu. Rev. Chem. Biomol. 8, 177–200 (2017).

6. J. W. Lee, J. H. Park, M. R. Prausnitz, Dissolving microneedles for transdermal drug delivery. Biomaterials 29, 2113–2124 (2008).

7. Banzhaf CA, Wind BS, Mogensen M, Meesters AA, Paasch U, Wolkerstorfer A, Haedersdal M. Spatiotemporal Closure of Fractional Laser-Ablated Channels Imaged by Optical Coherence Tomography and Reflectance Confocal Microscopy, Lasers Surg Med. 2016 Feb;48(2):157-65