Alexander Steimle, head of sales, FEMTOprint
Over the last decade, the medical industry has seen 3D printing technologies literally skyrocketing. The number of therapeutic cases where lives have been saved thanks to customised 3D printing demonstrates the potential that these technologies hold for healthcare in the near future; bioprinting of living tissues with blood vessels, customisable prosthetic sockets, drugs out of assembled chemical compounds at the molecular level, bones, heart valves, ear cartilage, synthetic skin and medical equipment are just a few of the applications that have been realised.
Most of these flourishing 3D printing technologies—for example, fused deposition modelling (FDM), selective laser sintering (SLS) and stereolithography (SLA)—are additive manufacturing (AM) practices where the first layer of material is put down, then a second is laid on top of this and a third and so on, until the final object is complete. The technologies vary in terms of their material melting, deposition and solidification methods.
While these technologies are evolving rapidly, there are still a number of limitations, such as: building speed; object size; precision and resolution; material strength and homogeneity; incompatibility with high temperatures or with living tissues such as the human body; and, in some cases, the need for mechanical support structures during fabrication and a post-processing step for residual removal and smoothing of the object’s surface. The question, then, is which technology can overcome these important fabrication drawbacks and tackle human diseases at micro-scale?
Typical requirements for medical micro-scale devices include: highly-precise geometries; low permeability; biocompatibility; material stability; resistance to high-temperatures, chemicals, scratches and corrosion; integration of optical, fluidic and mechanical features; conductive materials; surface functionalisation; and a reliable fabrication process, even at industrial level.
In the micromachining landscape, a more suitable technique—namely subtractive manufacturing—has gained significant success where high-precision, shape complexity and resolution are crucial factors for device functionalisation. In this context, FEMTOPRINT technology has proved an exceptional microfabrication technique. It is based on a two-step process of ultrashort pulsed laser radiation in transparent materials, followed by chemical wet etching to selectively remove the exposed material and form 3D shapes (figure 1).
Schematic view of the FEMTOPRINT process.
The laser beam, focused inside glass, locally modifies the refractive index of the material and creates patterns that can be used to realise integrated optical components or to develop, by chemical etching, even three-dimensional structures with high precision, aspect ratio and complexity.
The FEMTOPRINT technology platform is a standardised process compliant with ISO 13485:2016 Medical devices quality management system (QMS) requirements. As well as optical patterns and 3D components, complementary capabilities include: glass-to-glass encapsulation for body implants; hole drilling; glass cutting; and a self-developed polishing process to reduce surface roughness to below 10 nm Ra on free profiles and thus achieve the optical surface quality necessary for applications such as microlenses for endoscope imaging, lightning and laser-focusing.
The advantages of the technique allow for a drastic reduction in manufacturing steps, tools and costs. The direct writing process works in an out-of-cleanroom environment. It does not require masks or post-processing to remove residuals, and it is a versatile solution for rapid on-demand prototyping and serial productions, reducing new product development cycles.
The technology enables engineers to explore the third dimension of their devices at sub-micron resolution, facilitating feature-sized complexity and the integration of optical, mechanical, fluidic and even electrical functionalities, ultimately resulting in increased performances and reliability in a miniaturised space. The critical alignment of 2D micro-components and the time-consuming assembly steps are now overtaken issues. Adding more creativity and complexity, devices made using FEMTOPRINT technology can be coupled with complementary fabrication techniques, such as metal evaporation or sputtering, to create embedded electrodes, several new functionalisations to form hydrophobic or hydrophilic surfaces or coupling waveguides to build optofluidic devices.
Although glass has widespread technological usage and is the main starting material of the process, it is often negatively misjudged. At micro-scale, as an ordinary, amorphous material, it exhibits surprising properties, such as optical transparency, thermal and chemical stability, low thermal expansion, high elasticity (as is the case with optical fibres), biocompatibility, homogeneity and unusual dielectric properties—a powerful combination for new types of med-tech tools, biomedical chips with antibacterial surface treatments, micro-nozzles for nebulisers and dispensers, integrated optical devices and interconnects. Other areas of interest include micromechanical watch components with embedded microfluidic channels and springs.
In the med-tech industry, the capabilities of the technology significantly contribute to the improvement of medical engineering and therefore life quality.
FEMTOprint joined Galatea-Lab, EPFL (the Swiss Federal Institute of Technology in Lausanne), Switzerland, Instant-Lab, EPFL, Switzerland, and the Jules-Gonin ophthalmic hospital in Lausanne, Switzerland, in forming a consortium to develop a challenging, glass-based compliant puncture tool for retinal vein occlusion (RVO) (figure 2), a common retinal vascular disorder that affects 16 million people aged 50 and above globally and can cause severe loss of vision (figure 3).
1 of 2
Figure 2
Safe puncture tool made from a single glass substrate. (Source: Galatea-Lab and Instant-Lab)
2 of 2
Figure 3
Comparison of retinal veins and vision effect of healthy retina and RVO. (Source: Galatea-Lab and Instant-Lab)
RVO can be treated by cannulation and injection of therapeutic agents in the affected vein to remove clots that are limiting the oxygen transportation into the retina (figure 4). However, surgical cannulation of small retinal veins is considered very risky and challenging for multiple reasons, such as: fragility of the puncturing tissues; the required puncture force (~20 mN), which is well below human sensing capability; surgeon hand tremor; eye motion during surgery; and the dimensions of the tool, which need to be compatible with the vein1. Current medical treatments do not address the underlying cause of vein occlusion, rather they only treat the complications such as macular edema.
Schematic view of a retinal vein cannulation. (Source: Instant-Lab, EPFL; Project SPOT)
The consortium conceived, manufactured and tested a passive compliant tool for retinal vein cannulation (RVC), which relies on a buckling mechanical principle to safely and precisely cannulate veins in eye surgery, independent of the actuation input. This was made possible by taking advantage of the advanced manufacturing capabilities of FEMTOPRINT technology and glass properties such as robustness, favourable elasticity, transparency and biocompatibility. The element was fabricated entirely out of a fused silica monolith, which integrates three major features, namely:
- mechanical 3D cross pivots acting as bistable mechanisms (i.e. having two stable states and one unstable state);
- fluidic channels of only 70 µm ø in the needle tip to vehiculate drugs (figure 5); and
- optical elements to measure applied forces (figure 6).
1 of 2
Figure 5
Detail of the device. (Source: Instant-Lab, EPFL; Project SPOT)
2 of 2
Figure 6
Scanning electron microscope (SEM) image of the puncture tool. (Source: Galatea-Lab and Instant-Lab)
The bistable mechanism releases a constant amount of energy when it passes from its unstable state to a stable state2. It follows that a threshold force can be obtained by limiting the stroke of the mechanism (figure 7). This ensures safe and precise cannulation of the retinal vein, assuming a very thin wall, and with puncturing force lower than the threshold force, cannulation is guaranteed. The surgeon simply displaces the mechanism across its unstable state.
Strain energy reaction force of a bistable mechanism. (Source: Galatea-Lab and Instant-Lab)
Experiments conducted to-date have been very promising. The stability programming of the double-pinned bistable beam provides control over puncture force and stroke. The puncturing method has then been validated by way of finite element method (FEM) simulations and experimental measurements (figure 8), demonstrating several advantages for both the patient and the surgeon, namely:
- puncturing force is independent of surgeon force;
- actuation displacement is decoupled from puncturing position;
- it is insensitive to hand tremor; and
- it is also suitable for long injection times.
Experimental and numerical values of puncturing force and stroke for different tuning displacements. (Source: Galatea-Lab and Instant-Lab)
In an experimental trial, the tool successfully cannulated pig eye retinal veins (figure 9). In its final configuration, the surgical tool can be used in either standalone mode or mounted onto a robotic system.
Measurement setup of the experiment on a pig’s eye. (Source: Galatea-Lab and Instant-Lab)
The results of this challenging project demonstrated the ability to boost engineering creativity and design real 3D free forms, taking advantage of material properties to obtain medical applications at sub-micron resolution, with high accuracy and complexity, according to the ISO 13485:2016 medical device certification and industrial standards for large volumes throughput.
Acknowledgements
This work is funded by the Swiss Commission for Technology and Innovation (CTI), rebranded Innosuisse. FEMTOprint thanks all parties involved from Galatea Lab, Instant-Lab and the Jules-Gonin ophthalmic hospital for their support as well as Mohamed Zanaty and Thomas Fussinger, EPFL, for their contributions.
FEMTOprint
References
1Zanaty, M. et al. (2017). Safe puncture tool for retinal vein cannulation. Instant-Lab, EPFL. Available at: https://instantlab.epfl.ch/files/content/sites/instantlab/files/Documents/News/2018.01_laser%20technik%20journal/DMD_abstract_safe_puncture_tool_for_retinal_vein_cannulation.pdf
2 Henein, S. (2000). Design of articulated structures with high precision flexible guides, PhD thesis no. 2194, Infoscience EPFL scientific publications. Available at: https://infoscience.epfl.ch/record/32670?ln=en