In cell stretching, a mechanical model of the optically stretched cell is developed, based on which cell stiffness can be extracted and biomechanical property can be characterized. In cell positioning, based on dynamics analysis of the trapped cell in motion, a closed-loop controller is designed for cell transportation, which is further verified by experimental tests on live cells. These approaches successfully demonstrate the effectiveness of the robot-aided optical tweezers technology in cell manipulation. Please log in to get access to this content Log in Register for free.
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To get access to this content you need the following product:. Springer Professional "Technik" Online-Abonnement. Ashkin A Forces of a single-beam gradient laser trap on a dielectric sphere in the ray optics regime.
9. Cell Manipulation with Robot-Aided Optical Tweezers Technology
Biophys J 61 2 — CrossRef. Ashkin A, Dziedzic JM Optical trapping and manipulation of single cells using infra-red laser beams. Nature — CrossRef. Lab Chip — CrossRef. Nat Nanotechnol — CrossRef.
Optical Trapping and Optical Micromanipulation XIV, Conference Details
Darling EM, Zauscher S, Block JA, Guilak F A thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: do cell properties reflect metastatic potential? Biophys J — CrossRef. Greulich KO Micromanipulation by light in biology and medicine: the laser microbeam and optical tweezers.
J Biomed Opt 6 1 —22 CrossRef. Hertz HM Standing-wave acoustic trap for nonintrusive positioning of microparticles. J Appl Phys 78 8 — CrossRef. Hochmuth RM Micropipette aspiration of living cells. J Biomech —22 CrossRef. Hu Z, Wang J, Liang J Experimental measurement and analysis of the optical trapping force acting on a yeast cell with a lensed optical fiber probe. Opt Laser Technol — CrossRef.
Microfluidics-Based Laser Guided Cell-Micropatterning System
Hu S, Sun D, Feng G Dynamics analysis and closed-loop control of biological cells in transportation using robotic manipulation system with optical tweezers. Hu S, Sun D a Automated transportation of single cells using robot-tweezer manipulation system. Journal of Laboratory Automation 16 4 — CrossRef.
Fouriki et al. This method has been applied, with frequency dependent efficiency, to rat astrocytes as well as neural stem cell in suspensions Pickard and Chari, ; Adams et al. Adam et al. While the application of nanomagnetic forces has been well demonstrated in increasing transfection efficiency, further research needs to be done on the applications of oscillating magnetic fields.
Current research is indicative of a frequency dependent component of oscillatory magnetofection that it may be possible to optimize. Furthermore, magnetically targeting specific individual cell types within a cell population is specifically interesting to study disease models in vitro. The spatial limitation of magnetofection, however, currently remains a challenge, because the externally applied macro magnetic fields will always impose a spatial magnetic gradient across the entire cell culture platform.
The effect on other cells types within the same culture currently remains unknown. Thus, increasing spatial resolution and specificity of magnetic gradients down to single cell levels can be the focus of a variety of future studies. The purpose of this review was to highlight emerging applications of nanomagnetic forces and related concepts such as magnetic field effects and differences between permanent and alternating magnetic field stimulation on mammalian cell behavior.
We have discussed several advantages of nanomagnetic force stimulation over other force-mediating methods, however, we do need to acknowledge that our current understanding of nanomagnetic force stimulation has its limits. While magnetic field gradient can penetrate tissues, organs, or the human body it currently remains challenging to operate nanomagnetic forces in a controlled and precise manner through three-dimensional tissue constructs.
Furthermore, the response of cells to nanomagnetic force stimulation is limited in time. In the following, we would like to outline our opinion about how studies involving nanomagnetic force stimulation can address i spatiotemporal limitations of end-point experiments and ii bring this technology away from the bench and integrate it into mechanically-mediated diagnostics, pharmaceutical cell assays, and neurotherapeutics. Current studies about cell-based nanomagnetic force stimulation compare cell effects based on endpoint measurements or based on short time-windows of several minutes, as in the case of calcium stimulation.
It means that our current knowledge about nanomagnetic force stimulation in biological systems stems from either several minutes of live-cell experiments, or few day endpoint experiments 24 h and more without access to capture time-related intermediate data. From the endpoint measurements, we can conclude how nanomagnetic forces interfere with cells and which down- or upstreaming cell signals get activated or inhibited.
How cells, however, adjust temporally over a period of days or months to a potential nanomagnetic-based treatment requires a better understanding of the spatial-temporal relation between the force stimulus and the cellular, tissue and organ response. Systematic long-term experiments, where cell growth and behavior are constantly monitored using either optic, or electric measurements without interfering with the experimental setting, would allow us to learn more about spatio-temporal response of nanomagnetic forces stimulation.
Future nanomagnetic force-mediating studies may reveal new properties about the link between the force-mediating object and the cellular response. Figure 7A depicts two potential mechanism how the nanoparticle may translate the force stimulus to the cellular structure based on a direct or an associative link. The link between the nanomagnetic force stimulus and the subcellular object organelle, cell membrane, cytoskeleton impacts the time lag for the cellular response. If the nature of this link between the nanoparticle and the cellular structure is direct, the cellular response should be seen almost immediately.
After a force stimulus, the cell would need to at least interpret this stimulus in situ , if not triggering downstream signals immediately. In contrast, an associative link contains a storing capacity. The unloading of this capacity may or may not follow within the same time lag as for the direct link. It is more likely, however, that the storing capacity of the associative link triggers a cellular response within minutes, hours, or days. Thus, the time-lag will be an important parameter to better understand mechano-transduction and translational approaches in nanomagnetic force stimulation.
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Furthermore, Ricca et al. Within the context of our bound or associative nanoparticle which can be controlled through engineered surface coatings, the passive input can be modeled through an associative link and would show a delayed cellular response in comparison to the active, bound link.
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Concerning neurotherapeutic approaches, this delayed effect will be either desired, controlled, or prevented. Therefore, a deeper understanding of the spatio-temporal aspects of nanomagnetic force stimulation is essential to prepare this approach for further translational studies. Figure 7. Suggested future studies should address fundamental aspects of how nanomagnetic forces associate with cellular structures or how nanomagnetic force stimulation can be integrated into therapeutic and translational approaches.
A Protein-protein interactions are suggested to play a dominant role in nanomagnetic force activation and may determine how much force is required and how sensitive cells are to a biomechanical stimulus at the membrane. Depending on the surface functionality nanoparticles may interact with the cellular membrane in a weak associative or on a strong bound connection.
The strong bound connection suggests an immediate deformation of the membrane resulting in a short lag time to trigger a specific intracellular downstream process after a stimulus occurred. In contrast to the strong connection, the weaker associative connection may lead to a longer lag time or result in no further activation of downstream processes. B Other research efforts should focus on integrating nanomagnetic force stimulation into current neuromodulation tools, tissue engineering, organ functionality and translation into diagnostics, patient-specific therapeutics, or treatment predictions.
Our literature review focused on current single and multi-cell applications using nanomagnetic forces and related magnetic actuation concepts where we see a potential for translational applications regarding neurotherapeutics. In this last section, we want to provide to the reader an overview with the diverse potential of nanomagnetic force stimulation in translational research, neurotherapeutics and patient-specific prognostics Figure 7B. To truly realize the potential of nanomagnetic force stimulation, we need to go beyond single cell analysis and ask how nanomagnetic force stimulation will impact cell networks, specifically connected neuronal cell circuitries.
The next step toward neurotherapeutics is to incorporate nanomagnetic force stimulation into neural tissue engineering, Goldberg et al. The potential of adding magnetic force stimulation to tissue engineering lays in the properties of the nanoparticles to modulate cell mechanics Septiadi et al. The latter approach is beneficial to squeeze drugs out from a scaffold for a controlled duration during mechanically-force triggered drug delivery Zhang et al.
The transport of biopharmaceuticals through the blood brain barrier can further be promoted through magnetic force applications in combination with magnetoliposomes Thomsen et al. Adding nanomagnetic forces stimulation to neural grafts for spinal cord repair can be an alternative to optogenetic approaches Bryson et al. Finally, the differential uptake of magnetic nanoparticle into different brain cell types can be used to either selectively target and sort specific brain cell types, or to build controlled patterns of brain cells for artificial neural tissues.
Further translation of nanomagnetic force stimulation into brain issues and neurotherapeutics will also require a systematic understanding of brain cell functionality through metabolomics and proteomics Holle et al. Last, magnetic nanoparticles, which are the core of nanomagnetic forces are already common in cell sorting for cancer-based diagnostics, however, there is plenty of room to come up with new methods to integrate nanomagnetic forces into mechanically-mediated diagnostics and neuro- therapeutics based on protein chaperoning, separation, and on-chip cell technology.
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TG: Reviewed literature and wrote parts of the review paper; AK: Supervised, organized, reviewed literature and wrote this review paper. Both authors revised the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors would like to thank all Kunze Neuroengineering Lab members for scientific discussions and the members of the scientific writing group at MSU for feedback on the manuscript.
We also would like to thank the reviewers for their comments and time to improve our manuscript. Adams, C.