Micromanipulation for Electrophysiology, Biosensing and Genetic Engineering

Micromanipulators have revolutionized the way we study living cells and cellular systems. The technique uses high-precision tools, known as micromanipulators, in combination with a microscope, to delicately manipulate single cells or subcellular components. Micromanipulators allow researchers to interact with specimens in x, y and z directions with sub-micron resolution.

Fundamentals of Micromanipulation

Tools such as micropipettes, injectors, cutting tools, or electrodes are involved in micromanipulation. All of them can be mounted to the micromanipulator. The micromanipulator itself may be manual, hydraulic, or electrically motorized. When choosing the type and brand of a micromanipulator, it is important to consider the application and level of control required. As micromanipulators can be used in research institutions, hospitals, and biotech companies, they can be categorized by:

• Type: manual, hydraulic, or motorized
• Application: cell micromanipulation, electrophysiology
• User: academic researchers, clinicians, or industrial developers

Even minor movements at the human scale can cause significant disruption at the cellular level. Micromanipulators play a crucial role in minimizing such risks by enabling precise control during manipulation of microscopic structures. Their use also reduces variability, ensuring consistent and reproducible results in sensitive experimental workflows.

Micromanipulation in Electrophysiology

The focus of electrophysiology is measuring electrical activity of cells, specifically excitable ones such as neurons and cardiomyocytes. These measurements rely on detecting ion flow – typically sodium, potassium, or calcium – through membrane channels using precision electrode placement.

One of the most influential techniques in electrophysiology is the patch clamp, developed by Neher and Sakman in the 1970s. The technique offers insight into nerve ending activity, muscle contraction and more by measuring the ionic currents through a single ion channel or whole-cell membranes.

A typical patch clamp setup includes an inverted, upright microscope on an anti-vibration table, two manual micromanipulators holding either patch pipettes or stimulating electrodes, an amplifier system, and a perfusion chamber.

Patch clamp experiments rely heavily on precise, stable positioning of pipettes with micron-level accuracy, especially when it comes to the single-channel level. Ossila’s  manual micromanipulators offer the required stability needed for these recordings without introducing noise from motors or software errors. This is especially useful when paired with visual-based micromanipulation strategies, enabling researchers to navigate under high-magnification optics to isolate single-channel patches or achieve whole-cell configurations.

While micromanipulators are used in intracellular applications, they are also applicable for extracellular field recordings. One such example is epilepsy research in zebrafish models. This is because micromanipulators allow fine control of recording electrodes placed in neural tissue or brain slices.

Voltage clamp and patch clamp precision

In voltage clamp experiments, used in neuroscience, cardio physiology, endocrinology and microbiology, the membrane potential is held at a set value by specialised electronics, and the resulting ionic currents are measured. When conducting this experiment, it is important to keep in mind that these measurements are only accurate if the pipette and electrodes are positioned with exceptional precision. Therefore, it is recommended to use micromanipulators as they allow researchers to:

• Steadily bring micropipettes into contact with single cells
• Maintain membrane seals during whole-cell or cell-attached recordings
• Switch between "inside-out" or "outside-in" configurations for studying intracellular versus extracellular ion flow

Supporting Biosensor Development and Microfluidics

While micromanipulators are mostly used in experimental research, they are equally as important when developing and calibrating biosensors, especially when engineering electrochemical and microfluidic platforms. In these cases, the goal is often:

• Microelectrode positioning: Align sensor probes with microelectrodes or channels
• Sensor calibration: Place electrodes within microliter-volume solutions for calibration
• Microfluidic integration: Position PDMS microchannels on sensor substrates with micron-level alignment

An example of biosensor development are the hydrogen peroxide detection studies. In this case, researchers implement manual micromanipulators to calibrate platinum microelectrode arrays (Pt-MEAs) by positioning them in stirred solutions of known analyte concentration. Once calibrated, the same sensors can be used in cell culture wells to monitor oxidative bursts in real-time – again relying on the precision placement provided by the manipulator.

Microinjection and Genetic Research

What is microinjection?

Microinjection is a micromanipulation technique used to introduce foreign DNA, RNA, or proteins directly into the cell. The method uses fine glass micropipettes and controlled hydrostatic pressure, which offer high delivery precision, control over target location and compatibility with live-cell and embryo manipulation.

Applications

• Transgenic animal research: Injecting transgenic DNA into the pronucleus of a fertilized egg
• Single-cell genomics: Facilitates the isolation of rare cells from heterogeneous populations for transcriptomic analysis
• Gene delivery: Microinjection enables precise delivery of DNA, RNA, CRISPR-CAS9 complexes, and viral vectors into individual cells, minimizing off-target effects
• In vivo gene regulation: Studies like the one by Kizil et al. demonstrate the use of cerebroventricular microinjection (CVMI) in adult zebrafish to modulate gene expression

Micromanipulation in the Food Industry

Beyond biology and medicine, micromanipulation plays a growing role in food safety, microbiology, and fermentation technology. Applications within the food industry include:

• Single-cell isolation for identifying pathogens in complex food samples
• Yeast and bacterial strain improvement by injecting or modifying microbes used in brewing, dairy, and baking
• Probiotic engineering by enhancing strain survival and function
• Embryo and pollen micromanipulation for supporting hybrid crop production and embryo rescue in plant technology
• Pathogen detection by capturing individual bacterial cells for early identification during processing

If you are considering Ossila's micromanipulator for your next study, get in touch with us. Please include the details of your study and what micromanipulator characteristics you are looking for.

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