Research Projects

To manipulate fluids at pico-femto-liter volumes, we need devices with micro-nano-scale channels. We use photolithography and high-resolution 3D-printing techniques to fabricate suspended microfluidic devices. We also built fluid manipulation instruments. 

Funding: NWO-STW, NanoNextNL

Collaborators: Prof. Urs Staufer

Researchers: ir. Eleonoor Verlinden Dr. Jia Wei, ir. Xi Cao, ir. Robert Kramer, ir. Pieter van Altena, ir. Maarten Blankespoor, Gijs van der Gugten.

Publications: 

• Blankespoor, Maarten, et al. "Discrete Femtolitre Pipetting with 3D Printed Axisymmetrical Phaseguides." Small Methods (2023): 2300942.

• Kramer, Robert CLN, et al. "Multiscale 3D-printing of microfluidic AFM cantilevers." Lab on a Chip 20.2 (2020): 311-319.

• Verlinden, E. J., et al. "Volume and concentration dosing in picolitres using a two-channel microfluidic AFM cantilever." Nanoscale 12.18 (2020): 10292-10305.

• Cao, Xi, et al. "A model for controlled dosing of femto-litre volume liquids using hollow microcantilever." IFAC-PapersOnLine 50.1 (2017): 15542-15547.

• Ghatkesar, M. K, et al. "Scanning probe microscope-based fluid dispensing." Micromachines 5.4 (2014): 954-1001.

• Ghatkesar, M. K., Hector Hugo Perez Garza, and Urs Staufer. "Hollow AFM cantilever pipette." Microelectronic engineering 124 (2014): 22-25.

• Garza, Hector Hugo Perez, et al. "Enabling local deposition and controlled synthesis of Au-nanoparticles using a femtopipette." The 9th IEEE International Conference on Nano/Micro Engineered and Molecular Systems (NEMS). IEEE, 2014.

• Perez Garza, Hector Hugo, Murali Krishna Ghatkesar, and Urs Staufer. "Aspiration through hollow cantilever‐based nanopipette by means of evaporation." Micro & Nano Letters8.11 (2013): 758-761.

• Perez Garza, Hector Hugo, Murali Krishna Ghatkesar, and Urs Staufer. "Combined AFM—nanopipette cartridge system for actively dispensing femtolitre droplets." Journal of Micro-Bio Robotics 8.1 (2013): 33-40.

• Garza, HH Perez, et al. "Self-sensing nanopipette for liquid dispensing and AFM imaging." 2013 Transducers & Eurosensors XXVII: The 17th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS & EUROSENSORS XXVII). IEEE, 2013.

Most of the existing techniques involve destroying the cells and painstaking separation of the target sub-cellular constituents for analysis. There is a need for methods that can directly access the sub-cellular objects. We are investigating the use of microfluidic AFM cantilever to directly manipulate and extract sub-cellular components from an individual cell for further processing.

Funding: Convergence initiative 

Collaborators: Prof. Roland Kanaar (ErasmusMC), Prof. Silvére van der Maarel (LUMC), Dr. Anita van den Heuvel (LUMC)

Researchers: Dr. Tomas Manzaneque, Dr. Vijayendra Shastri, ir. Pieter van Altena

Advances in electron cryo-microscopy (cryo-EM) have made it possible to visualize the three-dimensional organization of a vitrified single cell with its dynamic internal structure immobilized in a native state at nanometer resolution. Major limitations that hinder wide use of this powerful technique are elaborate sample preparation protocols and the difficulty in identifying sample subvolumes of interest. We use microfluidic atomic force microscopy (AFM) devices to prepare cryo-EM samples by aspirating specific sub-volumes containing directly from inside a cell, and dispense them onto the EM sample grid for vitrification. Entire workflow of the sample prepartion of collecting single-cell biopsy, dispensing on an EM grid, and vitrification of the sample is built.  

Funding: NWO-STW, Nanosurf, SmartTip

Collaborators: Prof. Urs Staufer, Prof. Andreas Engel, Dr. Arjen Jakobi

Researchers: ir. Eleonoor Verlinden, Dr. Jochem Pronk, ir. Daniel Torres Gonzalez, Jelle van der Does, ir. Paul Laeven (Maastricht Instruments), Dr. Edin Sarajlic, Dr. Patrick Frederix (Nanosurf), Dr Vijayendra Shastri.

Publications:

• Pronk, Joachim Willem. "Aquaporin-2 trafficking: Studying cellular mechanisms with subcellular aspiration and cryo-electron microscopy." PhD Thesis

The key advantage of microfluidic chips is their size and the small fluid volumes used. However, the peripheral flow control systems are bulky losing all the advantages of miniaturization. Therefore, there is a major need for novel active microfluidic elements, detection schemes, control strategies and integration methodologies. The ambition of this effort is to build an integrated system consisting of pumps, valves and flow sensor. It should enable to eliminate bulky peripherals in microfluidics, thus laying the foundation for the envisaged integrated microfluidic sensors and actuators platform. 

Funding: TKI, Bronkhorst

Collaborators: Prof. Joost Lotters, Dr. Marcel Tichem

Researchers: Gurhan Ozkayar, Arun Gunda, Haoyu Zhu, Henri Kramer, Shiemaa Elhassan

Publications:

• Özkayar, Gürhan, et al. "Flow Ripple Reduction in Reciprocating Pumps by Multi-Phase Rectification." Sensors23.15 (2023): 6967.

• Zhu, Haoyu, et al. "Portable and integrated microfluidic flow control system using off-the-shelf components towards organs-on-chip applications." Biomedical microdevices 25.2 (2023): 1-11.

• Özkayar, Gürhan, et al. "Toward a modular, integrated, miniaturized, and portable microfluidic flow control architecture for organs-on-chips applications." Biomicrofluidics 16.2 (2022): 021302.

• Gunda, Arun, et al. "Proportional microvalve using a unimorph piezoelectric microactuator." Micromachines 11.2 (2020): 130.

By putting liquid inside a suspended channel, the inertial mass sensitivity of a resonator to detect floating objects inside liquid can be significantly increased. We fabricate silicon dioxide suspended microchannel resonators for mass sensing. They are used to measure density of fluids in picolitre volumes and buoyant mass of nanoparticles. We develop novel measurement schemes to minimize the noise in the measurement and push the limits of minimum detectable buoyant mass. 

Funding: NWO-STW, Marie-Curie Fellowship

Collaborators: Prof. Urs Staufer, Dr. Farbod Alijani, Prof. Peter Steeneken

Researchers: Dr. Paolo Belardinelli, Dr. Tomas Manzaneque, Dr. Jia Wei, ir. Savio DeSouza, ir. Shin Hur, ir. Mehdi Daryani, Jikke de Winter.

Publications:

• de Winter, et al. "Damping of 3D-printed polymer microbeam resonators." Journal of Micromechanics and Microengineering34.1 (2023): 015004.

• Manzaneque, Tomás, et al. "Resolution Limits of Resonant Sensors." Physical Review Applied 19.5 (2023): 054074.

• Daryani, Mehdi Mollaie, et al. "Measuring nanoparticles in liquid with attogram resolution using a microfabricated glass suspended microchannel resonator." Microsystems & Nanoengineering 8.1 (2022): 92.

• Manzaneque, Tomás, et al. "Method to determine the closed-loop precision of resonant sensors from open-loop measurements." IEEE Sensors Journal 20.23 (2020): 14262-14272.

• Belardinelli, Pierpaolo, et al. "Second flexural and torsional modes of vibration in suspended microfluidic resonator for liquid density measurements." Journal of Micromechanics and Microengineering 30.5 (2020): 055003.

• Belardinelli, P., et al. "Modal analysis for density and anisotropic elasticity identification of adsorbates on microcantilevers." Applied Physics Letters 113.14 (2018): 143102.

• Belardinelli, P., et al. "Linear and non-linear vibrations of fluid-filled hollow microcantilevers interacting with small particles." International Journal of Non-Linear Mechanics 93 (2017): 30-40.

Depending on how a cell interacts with the surrounding surface, it adapts itself accordingly. Understanding cell's biophysical characteristics will give insights  into their behaviour. We investigate adhesion strength and elastic modulus of individual cells using microfluidic force-sensitive cantilever and AFM.

Funding: Cohesion Grant, Marie-Curie Fellowship

Collaborators: Dr. Lidy Fratila-Apachitei 

Researchers: Dr. Livia Angeloni, ir. Bogdan Popa

Publications:

• Angeloni, Livia, et al. "Fluidic Force Microscopy and Atomic Force Microscopy Unveil New Insights into the Interactions of Preosteoblasts with 3D‐Printed Submicron Patterns." Small(2022): 2204662.

• Nouri-Goushki, Mahdiyeh, et al. "3D-printed submicron patterns reveal the interrelation between cell adhesion, cell mechanics, and osteogenesis." ACS Applied Materials & Interfaces 13.29 (2021): 33767-33781.

• Modaresifar, Khashayar, et al. "On the Use of Black Ti as a Bone Substituting Biomaterial: Behind the Scenes of Dual‐Functionality." Small 17.24 (2021): 2100706.

• Angeloni, L., et al. "Mechanical characterization of nanopillars by atomic force microscopy." Additive Manufacturing 39 (2021): 101858.

• Ganjian, Mahya, et al. "Quantitative mechanics of 3D printed nanopillars interacting with bacterial cells." Nanoscale 12.43 (2020): 21988-22001.

• Modaresifar, Khashayar, et al. "Deciphering the roles of interspace and controlled disorder in the bactericidal properties of nanopatterns against Staphylococcus aureus." Nanomaterials 10.2 (2020): 347.

• Nouri-Goushki, M., et al. "3D printing of large areas of highly ordered submicron patterns for modulating cell behavior." ACS applied materials & interfaces 12.1 (2019): 200-208.

Nanoscale sensors are known for their sensitivity due to their small size. However, to make the sensors active to the analytes of interest, they should be functionalized with sensitive layer of coatings. We investigate methods to functionalze nanoscale sensors with various fluid manipulation methods. 

Funding: TKI

Collaborators: Prof. Frans Widdershoven, Prof. Peter Steeneken

Researchers: Dr. Kaï Bethlam

Publications: 

• Sartori, André F., et al. "Inkjet‐Printed High‐Q Nanocrystalline Diamond Resonators." Small 15.4 (2019): 1803774.

• Waasdorp, Rick, et al. "Accessing individual 75-micron diameter nozzles of a desktop inkjet printer to dispense picoliter droplets on demand." RSC advances 8.27 (2018): 14765-14774.