Investigation of Automated Cell Manipulation in Optical Tweezers-Assisted Microfluidic Chamber Using Simulations

Author(s):  
Sagar Chowdhury ◽  
Petr Svec ◽  
Chenlu Wang ◽  
Kevin T. Seale ◽  
John P. Wikswo ◽  
...  

Microfluidic devices are well suited for the study of biological objects because of their indirect nature of manipulation and high throughput. However, the cell manipulation process solely depends on the fluid flow and hence precise control is difficult to attain inside a microfluidic chamber. Utilizing optical tweezers as a complementary tool provides precise manipulation control. We have presented an automated cell manipulation approach using optical tweezers operating inside a microfluidic chamber. To test and demonstrate the effectiveness of the approach we have developed a physics-based simulator that is completely automated and allows high precision of manipulation.

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
MI Khot ◽  
M Levenstein ◽  
R Coppo ◽  
J Kondo ◽  
M Inoue ◽  
...  

Abstract Introduction Three-dimensional (3D) cell models have gained reputation as better representations of in vivo cancers as compared to monolayered cultures. Recently, patient tumour tissue-derived organoids have advanced the scope of complex in vitro models, by allowing patient-specific tumour cultures to be generated for developing new medicines and patient-tailored treatments. Integrating 3D cell and organoid culturing into microfluidics, can streamline traditional protocols and allow complex and precise high-throughput experiments to be performed with ease. Method Patient-derived colorectal cancer tissue-originated organoidal spheroids (CTOS) cultures were acquired from Kyoto University, Japan. CTOS were cultured in Matrigel and stem-cell media. CTOS were treated with 5-fluorouracil and cytotoxicity evaluated via fluorescent imaging and ATP assay. CTOS were embedded, sectioned and subjected to H&E staining and immunofluorescence for ABCG2 and Ki67 proteins. HT29 colorectal cancer spheroids were produced on microfluidic devices using cell suspensions and subjected to 5-fluorouracil treatment via fluid flow. Cytotoxicity was evaluated through fluorescent imaging and LDH assay. Result 5-fluorouracil dose-dependent reduction in cell viability was observed in CTOS cultures (p<0.01). Colorectal CTOS cultures retained the histology, tissue architecture and protein expression of the colonic epithelial structure. Uniform 3D HT29 spheroids were generated in the microfluidic devices. 5-fluorouracil treatment of spheroids and cytotoxic analysis was achieved conveniently through fluid flow. Conclusion Patient-derived CTOS are better complex models of in vivo cancers than 3D cell models and can improve the clinical translation of novel treatments. Microfluidics can streamline high-throughput screening and reduce the practical difficulties of conventional organoid and 3D cell culturing. Take-home message Organoids are the most advanced in vitro models of clinical cancers. Microfluidics can streamline and improve traditional laboratory experiments.


2019 ◽  
Vol 9 (14) ◽  
pp. 2883 ◽  
Author(s):  
Songyu Hu ◽  
Heng Xie ◽  
Tanyong Wei ◽  
Shuxun Chen ◽  
Dong Sun

Optical tweezers are widely used for noninvasive and precise micromanipulation of living cells to understand biological processes. By focusing laser beams on cells, direct cell manipulation with optical tweezers can achieve high precision and flexibility. However, direct exposure to the laser beam can lead to negative effects on the cells. These phenomena are also known as photobleaching and photodamage. In this study, we proposed a new indirect cell micromanipulation approach combined with a robot-aided holographic optical tweezer system and 3D nano-printed microtool. The microtool was designed with a V-shaped head and an optical handle part. The V-shaped head can push and trap different sizes of cells as the microtool moves forward by optical trapping of the handle part. In this way, cell exposure to the laser beam can be effectively reduced. The microtool was fabricated with a laser direct writing system by two-photon photopolymerization. A control strategy combined with an imaging processing algorithm was introduced for automated manipulation of the microtool and cells. Experiments were performed to verify the effectiveness of our approach. First, automated microtool transportation and rotation were demonstrated with high precision. Second, indirect optical transportations of cells, with and without an obstacle, were performed to demonstrate the effectiveness of the proposed approach. Third, experiments of fluorescent cell manipulation were performed to confirm that, indicated by the photobleaching effect, indirect manipulation with the microtool could induce less laser exposure compared with direct optical manipulation. The proposed method could be useful in complex biomedical applications where precise cell manipulation and less laser exposure are required.


Micromachines ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 90 ◽  
Author(s):  
Ivan Shishkin ◽  
Hen Markovich ◽  
Yael Roichman ◽  
Pavel Ginzburg

Advances in laser and optoelectronic technologies have brought the general concept of optomechanical manipulation to the level of standard biophysical tools, paving the way towards controlled experiments and measurements of tiny mechanical forces. Recent developments in direct laser writing (DLW) have enabled the realization of new types of micron-scale optomechanical tools, capable of performing designated functions. Here we further develop the concept of DLW-fabricated optomechanically-driven tools and demonstrate full-3D manipulation capabilities over biological objects. In particular, we resolved the long-standing problem of out-of-plane rotation in a pure liquid, which was demonstrated on a living cell, clamped between a pair of forks, designed for efficient manipulation with holographic optical tweezers. The demonstrated concept paves the way for the realization of flexible tools for performing on-demand functions over biological objects, such as cell tomography and surgery to name just few.


2006 ◽  
Vol 20 (06) ◽  
pp. 659-666
Author(s):  
YUQIANG JIANG ◽  
HONGLIAN GUO ◽  
CHUNXIANG LIU ◽  
ZHAOLI LI ◽  
BINGYING CHENG ◽  
...  

In an optical tweezers system, the output signal of a photodiode quadrant detector and the temperature in a sample cell are two key factors for the quantitative measurements of mechanical properties of living biological objects such as cells, organelles and macro-molecules. In order to enhance the output of a quadrant detector and effectively control the temperature in a sample cell, the dependence of the temperature in the sample cell and the output of the quadrant detector for different illumination conditions are studied. The results show that appropriate illumination conditions can ensure both nearly constant temperatures in the cell and the desired output signal, which provides for the possibility of high precision and damage-free analysis of living biological objects.


Lab on a Chip ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 1454-1474
Author(s):  
H. Azizgolshani ◽  
J. R. Coppeta ◽  
E. M. Vedula ◽  
E. E. Marr ◽  
B. P. Cain ◽  
...  

96 microfluidic devices with independent electrical readouts are coupled with 192 micropumps to make a high-throughput organ-on-chip platform.


Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S97
Author(s):  
J. Bell ◽  
Y. Huang ◽  
S. Yung ◽  
H. Qazi ◽  
C. Hernandez ◽  
...  

2021 ◽  
Vol 7 (6) ◽  
pp. eabe3902
Author(s):  
Martin Rieu ◽  
Thibault Vieille ◽  
Gaël Radou ◽  
Raphaël Jeanneret ◽  
Nadia Ruiz-Gutierrez ◽  
...  

While crucial for force spectroscopists and microbiologists, three-dimensional (3D) particle tracking suffers from either poor precision, complex calibration, or the need of expensive hardware, preventing its massive adoption. We introduce a new technique, based on a simple piece of cardboard inserted in the objective focal plane, that enables simple 3D tracking of dilute microparticles while offering subnanometer frame-to-frame precision in all directions. Its linearity alleviates calibration procedures, while the interferometric pattern enhances precision. We illustrate its utility in single-molecule force spectroscopy and single-algae motility analysis. As with any technique based on back focal plane engineering, it may be directly embedded in a commercial objective, providing a means to convert any preexisting optical setup in a 3D tracking system. Thanks to its precision, its simplicity, and its versatility, we envision that the technique has the potential to enhance the spreading of high-precision and high-throughput 3D tracking.


2006 ◽  
Vol 13 (06) ◽  
pp. 795-802 ◽  
Author(s):  
DANIEL LIM ◽  
ERNA GONDO SANTOSO ◽  
KIM MING TEH ◽  
STEPHEN WAN ◽  
H. Y. ZHENG

Silicon has been widely used to fabricate microfluidic devices due to the dominance of silicon microfabrication technologies available. In this paper, theoretical analyses are carried out to suggest suitable laser machining parameters to achieve required channel geometries. Based on the analyses, a low-power CO 2 laser was employed to create microchannels in Acrylic substrate for the use of manufacturing an optical bubble switch. The developed equations are found useful for selecting appropriate machining parameters. The ability to use a low-cost CO 2 laser to fabricate microchannels provides an alternative and cost-effective method for prototyping fluid flow channels, chambers and cavities in microfluidic lab chips.


Author(s):  
Maura C. Kibbey ◽  
David MacAllan ◽  
James W. Karaszkiewicz

IGEN's ORIGEN® technology, which is based on electrochemiluminescence, has been adopted by a number of research and bioanalytical laboratories who have recognized its exquisite sensitivity, high precision, wide dynamic range, and flexibility in formatting a wide variety of applications. IGEN's M-SERIES™ marks the introduction of the second generation of detection systems employing the ORIGEN technology specifically repackaged to address the needs of the high throughput laboratories involved in drug discovery. Assays are formatted without wash steps. Users realize the high performance of a heterogeneous technology with the convenience of a homogeneous format. The M-SERIES platform can address enzymatic assays (kinases, proteases, helicases, etc.), receptor-ligand or protein-protein assays, immunoassays, quantitation of nucleic acids, as well as other applications. Recent assay formats will be explored in detail.


2011 ◽  
Vol 134 (2) ◽  
Author(s):  
V. V. Dharaiya ◽  
S. G. Kandlikar

Study of fluid flow characteristics at microscale is gaining importance with shrinking device sizes. Better understanding of fluid flow and heat transfer in microchannels will have important implications in electronic chip cooling, heat exchangers, MEMS, and microfluidic devices. Due to short lengths employed in microchannels, entrance header effects can be significant and need to be investigated. In this work, three dimensional model of microchannels, with aspect ratios (α = a/b) ranging from 0.1 to 10, are numerically simulated using CFD software tool fluent. Heat transfer effects in the entrance region of microchannel are presented by plotting average Nusselt number as a function of nondimensional axial length x*. The numerical simulations with both circumferential and axial uniform heat flux (H2) boundary conditions are validated for existing data set for four wall heat flux case. Large numerical data sets are generated in this work for rectangular cross-sectional microchannels with heating on three walls, two opposing walls, one wall, and two adjacent walls under H2 boundary condition. This information can provide better understanding and insight into the transport processes in the microchannels. Although the results are seen as relevant in microscale applications, they are applicable to any sized channels. Based on the numerical results obtained for the whole range, generalized correlations for Nusselt numbers as a function of channel aspect ratio are presented for all the cases. The predicted correlations for Nusselt numbers can be very useful resource for the design and optimization of microchannel heat sinks and other microfluidic devices.


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