Micromanipulation uses microsurgical techniques to study and alter the structure or composition of single living cells or a group of cells under a microscope. It involves a specialized microscope called micromanipulator which comprises tiny glass tools attached to robotic arms that are driven by an electric motor. These microtools have very small tips that do not allow the abrupt or gross movements that commonly occur during human handling of microscopic specimens.
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Different methods of micromanipulation
This is a micromanipulation technique used to deliver foreign DNA with the help of a micropipette using hydrostatic pressure. These injections are usually carried out under a powerful microscope for precision delivery of DNA. Micromanipulation methods are also classified based on their type, application and targeted end-user:
- Micromanipulation by application - includes in vitro fertilization (IVF) technology, cell micromanipulation, and electrophysiology.
- Micromanipulation by type - includes hydraulic, manual, or electric micromanipulation.
- Micromanipulation based on the targeted end-user - includes use in hospitals, fertility clinics, as well as in research institutes.
Applications of micromanipulation techniques
Micromanipulation in the food industry
There is an increasing demand for thorough, low-cost quality control techniques that can certify a food item to be safe for consumption. In some cases, conventional methods of food safety are being replaced by micromanipulation techniques to test food products for gram-negative and gram-positive microbes.
Transgenic animal production
With the help of micromanipulation, several transgenic animals have been produced such as sheep, rabbits, and pigs. For instance, a transgenic mouse with a large body weight was produced by Palmiter et al. in 1982 by injecting the mouse embryo with a DNA fragment containing the rat growth hormones that were fused to the metallothionein I gene.
Micromanipulators are being used extensively in combination with extracellular field recording in the study of epilepsy in rodents and vertebrate models such as zebrafish. Zebrafish have a genetic profile that exhibits a high degree of similarity with that of mammals, thereby making it easier to study gene mutation, knockdown, or genetic defects responsible for epileptic seizures.
Genetics and gene therapy
A study by Kizil et al. was carried out to understand how micromanipulation could be used in gene regulation. The study used the brain of an adult Zebra fish and introduced antisense morpholino oligonucleotides by cerebroventricular microinjection (CVMI) to knock down in vivo gene expression.
Kizil et al. concluded that CVMI is an efficient technique for understanding adult neurogenesis and may help clinically in paving way for treatment of neurodegenerative disorders. At present, micromanipulation procedures are frequently used to carry out embryo biopsies to rule out any fetal anomalies due to a genetic disorder.
Single-molecule micromanipulation has also proved to be of immense value in study of DNA and structural proteins enabling study of various parameters of individual proteins, such as binding and unbinding kinetics.
Micromanipulation has been especially useful in IVF in assisting embryo hatching in women who have issues with embryo implantation. These micromanipulation techniques are also used to assist fertilization in case of male infertility by a procedure known as intracytoplasmic sperm injection (ICSI). In ICSI, the sperm is placed in direct contact with the egg using micromanipulation to enhance the chances of fertilization of a healthy embryo.
Rahman et al have demonstrated in their study that cooperative micromanipulation using individual and groups of microrobots moving in linear, circular, and arbitrary 2-dimensional routes can be used in tissue engineering to assemble mesoscale structures under microscale resolution.
Cooperative micromanipulation offers reduces the time needed to complete tasks such as delivery of numerous micro-objects. This method could be of immense value in clinical diagnostics.
- Zhang, J. & Xu, K. (2009). Intracytoplasmic Sperm Injection and Other Micromanipulation Techniques for Assisted Reproduction. Glob. Libr. Women's Med. doi.org/10.3843/GLOWM.10369
- Hohnadel M, Maumy M., and Chollet R. Development of a micromanipulation method for single cell isolation of prokaryotes and its application in food safety. PLOS ONE. 2018 May;13(5):e0198208. doi.org/10.1371/journal.pone.0198208.
- Kizil C, Lltzsche A, Kaslin J et al. Micromanipulation of Gene Expression in the Adult Zebrafish Brain Using Cerebroventricular Microinjection of Morpholino Oligonucleotides. J Vis Exp. 2013;(75):50415. doi.org/10.3791/50415
- Rahman MA, Cheng J, Wang Z et al. Cooperative Micromanipulation Using the Independent Actuation of Fifty Microrobots in Parallel. Scientific Reports. 2017 Jun;7:3278. doi.org/10.1038/s41598-017-03525-y.