Force-controlled manipulation of single cells: from AFM to FluidFM

Guillaume‐Gentil, Orane; Potthoff, Eva; Ossola, Dario; Franz, Clemens M.; Zambelli, Tomaso; Vorholt, Julia A.

doi:10.1016/j.tibtech.2014.04.008

Cited by 193 publications

(170 citation statements)

References 89 publications

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“…For example, we can assess the drugs (single agents or combination agents) by quantitatively monitoring the morphological and mechanical changes on single cells after drug stimulations. Especially recent studies have shown that AFM can deliver drugs into single cells via the assistance of nanofluidics [57]. Compared with traditional drug assay methods, the AFM-based label-free drug assay method will have many advantages, such as inexpensive (requires only a small amount of cells and drugs), fast (several hours), and accurate (focusing on the nanoscale changes of single cells after the stimulation of controlled amount of drugs).…”

Section: Resultsmentioning

confidence: 99%

Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

Xiao

Liu

et al. 2016

IEEE Trans. Biomed. Eng.

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Abstract-The applications of targeted drugs in treating cancers have significantly improved the survival rates of patients. However, in the clinical practice, targeted drugs are commonly combined with chemotherapy drugs, causing that the exact contribution of targeted drugs to the clinical outcome is difficult to evaluate. Quantitatively investigating the effects of targeted drugs on chemotherapy drugs on cancer cells is useful for us to understand drug actions and design better drugs. The advent of atomic force microscopy (AFM) provides a powerful tool for probing the nanoscale physiological activities of single live cells. In this paper, the detailed changes in cell morphology and mechanical properties were quantified on single lymphoma cells during the actions of rituximab (a monoclonal antibody targeted drug) and two chemotherapy drugs (cisplatin and cytarabine) by AFM. AFM imaging revealed the distinct changes of cellular ultramicrostructures induced by the drugs. The changes of cellular mechanical properties after the drug stimulations were measured by AFM indenting. The statistical histograms of cellular surface roughness and mechanical properties quantitatively showed that rituximab could remarkably strengthen the killing effects of chemotherapy drugs. The study offers a new way to quantify the synergistic interactions between targeted drugs and chemotherapy drugs at the nanoscale, which will have potential impacts on predicting the efficacies of drug combinations before clinical treatments.

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Section: Resultsmentioning

confidence: 99%

Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

Xiao

Liu

et al. 2016

IEEE Trans. Biomed. Eng.

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“…There is a strong desire among researchers to directly observe molecular processes occurring in the cell without using optical markers, raising the question of whether it is possible to look at the cell interior with HS-AFM. It has already been demonstrated that the long tip (even a thin pipette) can be inserted into the cell without killing the cell (Obataya et al 2005;Guillaume-Gentil et al 2014). However, no one has tried to carry out AFM imaging of the cell interior.…”

Section: Nano-endoscopymentioning

confidence: 99%

High-speed atomic force microscopy and its future prospects

2017

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Various techniques have been developed and used to investigate how proteins produce complex biological architectures and phenomena. Among these techniques, high-speed atomic force microscopy (HS-AFM) holds a unique position. It is only HS-AFM that allows the simultaneous assessment of structure and dynamics of single protein molecules in action. This new microscopy tool has been successfully applied to a variety of proteins, from motor proteins to membrane proteins, antibodies, enzymes, and even to intrinsically disordered proteins. And yet there still remain many biomolecular phenomena that cannot be addressed by HS-AFM in its current form. Here, I present a brief history of HS-AFM development, describe the current state of HS-AFM, and then discuss which new biological scanning probe microscopy techniques will be coming up next.

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“…Currently, living cells cannot be observed by ESEM under the physiological conditions [36]. In contrast, AFM can work in liquids, enabling robotic manipulations on single living cells under physiological conditions [37], such as drug injection [38], nanodissection [39], nanoindentation [40] and nanovisualization [41]. Hence, AFM-based nanomanipulator is particularly suited for biological applications at the nanometer scale.…”

Section: Blueprint Of Micro/nano Automation In Personalized Cancementioning

confidence: 99%

Applications of Micro/Nano Automation Technology in Detecting Cancer Cells for Personalized Medicine

Liu

et al. 2017

IEEE Trans. Nanotechnology

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Abstract-The coming era of personalized cancer treatment is presenting automation with unprecedented opportunities. Currently, the drug susceptibility test of clinical cancer patients is mainly dependent on manual labor with a low level of automation. Automating the process of primary cancer cell detection will potentially have tremendous economic benefits and social significance. Automated cancer cell detection means developing robotic and automation equipments to handle single cells and molecules at the micro/nanometer-scale. The achievements of information science, engineering technology, life sciences, and nanotechnology in the past decades have led to the birth of robots that can perform effective manipulations on single living cells at the micro/nanometerscale in aqueous conditions, opening the door to automated cancer cell detection. However, there is still a huge gap between current single-cell micro/nano automation technology and clinical requirements for personalized medicine. In this paper, we will review the progress of single-cell micro/nano automation technology in recent years and discuss the facing challenges and future directions in three aspects, including automated cell isolation and delivery, automatically acquiring the physiological features of cells and data analysis.

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Force-controlled manipulation of single cells: from AFM to FluidFM

Cited by 193 publications

References 89 publications

Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

High-speed atomic force microscopy and its future prospects

Applications of Micro/Nano Automation Technology in Detecting Cancer Cells for Personalized Medicine

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