Introduction: Pushing the Frontiers of Stem Cell and Regenerative Medicine
The Institute for Stem Cell and Regeneration (ISCR), Chinese Academy of Sciences (CAS), is one of China's premier national research platforms dedicated to cutting-edge advances in stem cell biology, regenerative medicine, gene editing, and related frontier fields.
Jointly established by the Chinese Academy of Sciences and local governments (including Beijing and Guangdong), the institute brings together the strengths of multiple CAS-affiliated research units. It forms a full-chain innovation ecosystem spanning basic research, technology development, and clinical translation, with a mission to tackle major medical challenges such as organ transplantation shortages and degenerative disease treatments, and to accelerate the growth of the biomedicine industry.
The institute includes major branches such as the Beijing Institute of Stem Cell and Regenerative Medicine and the Guangzhou Institutes of Biomedicine and Health, along with multiple collaborative centers. Core research areas include:
- Cell fate control
- Induced pluripotent stem cell (iPSC) technologies
- Fully automated stem cell culture systems
- Organoid engineering and cross-species organ transplantation
- Innovative drug discovery
Among its many notable achievements are breakthroughs in stem cell induction, organ regeneration, major disease therapy, and the development of standardized and internationally recognized biomedical equipment.
Innovating with CNC: Building Advanced Microfluidic Devices
In its latest work, the ISCR team is using CNC machining in a highly specialized application: fabricating molds for microfluidic blood-brain barrier (BBB) models.
This project leverages the Makera Carvera desktop CNC machine to create ultra-precise molds that enable the self-assembly of vascular networks within microfluidic devices. Specifically, the Carvera is used to produce central gel channel structures within the devices, critical for ensuring consistent, physiologically relevant microvascular formation, which is essential for cell culture and advanced drug permeability studies.
Key project needs include:
- High precision and repeatability of microchannel structures, enabling accurate simulation of biological vascular networks.
- Dual applications:
- Macrodevices for high-throughput experimentation and downstream analysis.
- Microdevices for high-resolution imaging.
The Carvera-based workflow is a critical manufacturing step, enabling complex 3D vascular modeling and facilitating advanced experiments in regenerative medicine and neuroscience.
Fabrication Workflow with Makera Carvera
To meet the project's stringent requirements, the team developed a precise CNC-based mold fabrication process:
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Mold Design
- CAD software is used to design channel structures that match physiological vessel dimensions (diameters of 10–40 μm).
- Macrodevice channels are optimized to reduce molecular diffusion interference. -
CNC Machining
- The Carvera is used to engrave micron-precision negative templates into high-hardness materials.
- Surface smoothness is critical to ensure defect-free PDMS replication. -
PDMS (Polydimethylsiloxane) Replication
- Liquid PDMS is poured into the CNC mold, cured, and then peeled off to yield PDMS chips with embedded channel structures.
- Final steps include punching inlets/outlets and bonding the chip to a glass substrate.
Compared to traditional photolithography (which is limited to planar structures) or 3D printing (which often lacks the required resolution), CNC machining with the Carvera provides a high-precision, flexible, and reproducible solution for both macro- and microdevice fabrication.
In-Depth Q&A with Junkai Zhang, PhD student, Institute for Stem Cell and Regeneration, CAS
To gain deeper insights, we spoke with Junkai Zhang, a PhD student at ISCR and a key member of the vascular modeling project. Here is his perspective on the role of Makera CNC in their research:
Q1: What were the specific demands for those research molds?
For our medical research project, the mold precision requirements are extremely high. For example, the requirement of channel height is typically only 500 microns, and some even finer structures are only 150 microns, with the narrowest partial walls at just 50 microns. At these dimensions, even the slightest margin of error could affect the arrangement of cells or the flow path of liquids, impacting the results of the experiment.
Additionally, the molds need a smooth surface so that when we demold the PDMS (Polydimethylsiloxane), it wouldn’t tear or leave small burrs, which could affect the integrity of the microfluidic channels. Most importantly, the flatness of the mold directly impacts the bonding of the PDMS to the glass slide, which is crucial for the chip’s functionality and the reliability of the entire experiment.
Q2: Before using a desktop CNC like the Carvera, what kinds of difficulties did your team face? Have you used other tools such as 3D printing or photo etching? What problems did you encounter?
We thought about using a traditional large CNC machine, but it's bulky, takes up a lot of space, and isn't suited for our lab environment. Plus, its setup is quite complicated, and it requires a high level of expertise, which doesn’t help us with quick modeling iterations.
We also considered using soft lithography techniques, but the equipment is expensive, and the molds tend to deform, causing issues like bubbles or leaks when bonding the PDMS layer to the glass slide.
Talking about 3D printing, while convenient, we found that it leaves noticeable layer lines on the mold surface, and the precision isn’t enough to meet our needs. So it didn’t work for our experiments.
Q3: Have you ever used other CNC machines to process molds? What problems and difficulties did you encounter?
We have tried a few other desktop CNC machines, but most of them can only achieve an accuracy of ±100μm or more, which is far from sufficient for our micron-level needs. On top of that, the operator has to manually change the tools, which not only increases the chance of errors but also lowers our efficiency.
Q4: What are your favorite features or functions of the Carvera?
The Carvera offers several key features that attract us. Firstly, its machining precision is excellent, with the X/Y axis at ±5μm and the Z axis at ±10μm, which is perfect for microfluidic mold manufacturing.
Second, it supports automatic tool changing, eliminating manual intervention and enabling seamless transitions between rough and fine machining, which greatly improves efficiency. We use a variety of tools for machining molds, and the Carvera can automatically and precisely switch between them to make sure we get the best result.
Another major advantage is its great compatibility with design software. It supports direct NC output from platforms like Fusion 360 and Autodesk programs we use, making the entire process incredibly smooth.
Q5: Why did you choose the Carvera over other solutions or CNC machines? Are there specific features that stand out?
The Carvera is a "plug-and-play" tool for research teams like us.
Compared to traditional CNC, the Carvera is a compact desktop model, taking up less than a square meter, and it can be easily placed on a lab bench.
Furthermore, what impressed us most is that the Carvera is fully automated, everything from probing and calibration work to tool changing and dust collection, all built-in, meaning we rarely need to intervene during the machining process, which boosts our productivity significantly.
Q6: Could you briefly introduce your research project and how the Carvera contributes to it?
We successfully used the Carvera to manufacture a classic three-channel vascular chip mold, using POM as the material. The Carvera handles this material very well。
PDMS demolding goes smoothly with a high yield, and we can produce multiple chips in a single batch. Since the mold surface is smooth, the POM doesn’t deform, which solves the bonding issues we had with uneven mold surfaces, perfectly matching our design expectations.
Q7: Could you walk us through a real mold fabrication process with the Carvera — how did you ensure micron-level precision?
For our three-channel vascular chip mold, the process with the Carvera is closely integrated. First, we design the model in AutoCAD, then import it into Fusion 360 along with the Carvera’s machine library, tool library, and post-processing library. After generating the tool paths and NC code, we upload them to the Carvera’s software and double-check the tool settings for each step. Once everything’s set, we can start machining directly.
Q8: Can you share how the geometric accuracy of these molds impacted your experimental data?
The geometric accuracy of the mold geometry directly affects how well the PDMS layer bonds to the glass slide. If the mold is uneven, it leads to bubbles, leakage, and poor bonding, rendering the chip useless. We validate this with permeability experiments – chips made from high-precision molds have excellent bonding, and their solute diffusion rates are comparable to the permeability of real blood vessels.
Q9: How has having an in-house desktop CNC accelerated your team’s progress? What impact has it had on research outcomes (cost/time savings, custom solutions, noise/dust control)?
The three-channel self-assembling vascular chip we make with the Carvera accurately replicates physiological structures. Specifically, the blood vessels are fully continuous, with characteristics similar to real microvessels, including scale, permeability, and cell-to-cell interactions. This makes it perfect for drug permeability testing. The Carvera provides reliable mold manufacturing throughout the process, ensuring smooth experiments and leading to groundbreaking results.
Q10: What advice would you give to research labs and academic peers considering a desktop CNC? What value and benefits can the Carvera bring to them?
The Carvera lowers the barrier for mold development in our experiments. Its high precision and automation significantly reduce the trial-and-error costs and the difficulty of use. So far, we’ve used the Carvera to make nearly 20 different molds, and not once have we had a failure. Every mold is perfectly matched for subsequent experiments. I’d highly recommend a Carvera CNC to our peers, especially in fields that require high precision – The Carvera is a great addition to any lab.
Q11: If you could summarize Carvera in a few words or phrases, what would they be?
Precise. Automated. Lab-friendly.
Conclusion: Expanding the Frontiers of Regenerative Medicine with CNC Innovation
By integrating desktop CNC machining into its cutting-edge vascular modeling work, the Institute for Stem Cell and Regeneration, CAS is breaking new ground in regenerative medicine and microfluidic device fabrication.
The Makera Carvera offers unmatched precision, automation, and flexibility, enabling Junkai Zhang and the ISCR team to advance their research while saving time, reducing costs, and enhancing experimental reproducibility.
As regenerative medicine continues to evolve, CNC tools like the Carvera will play an ever more vital role in helping researchers bring new biomedical innovations to life.
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