Holographic Tweezers: Positioning Living Stem Cells in 3D Using LabVIEW

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"We used LabVIEW to rapidly develop a new breed of instrument for studying stem cells at length scale, offering biological insights that were not previously achievable."

- Glen Kirkham, School of Pharmacy, University of Nottingham

The Challenge:
Cells, the fundamental building blocks of life, exist in complex microenvironments. The accurate study of these structures is limited by the lack of technologies that can manipulate cells in 3D at a sufficiently small length scale. Developing such a tool will facilitate a detailed understanding of cellular function, and accelerate the development of future medicines and treatments.

The Solution:
Using LabVIEW and the Vision Development Module to create a sophisticated platform, which uses infrared laser energy to simultaneously position multiple stem cells. Our LabVIEW interface allows users to position individual cells in 3D through simple mouse movements, which empowers scientists to study cellular microenvironments in unprecedented detail.

Author(s):
Glen Kirkham - School of Pharmacy, University of Nottingham
Graham Gibson - School of Physics and Astronomy, University of Glasgow
Miles Padgett - School of Physics and Astronomy, University of Glasgow
Lee Buttery - School of Pharmacy, University of Nottingham
Kevin Shakesheff - School of Pharmacy, University of Nottingham

Cells are the basic functional unit of all living organisms. In all parts of the human body, cells exist in tiny, complex worlds, each tirelessly working to keep you alive and functioning. Cell biology, the scientific branch that studies the fundamental building blocks of life, has existed since the discovery of the cell in the 17th century. Yet, despite hundreds of years of research, there are unanswered questions regarding what these tiny worlds look like and how individual cells live and work within them. The gaps in our knowledge are due to these cellular microenvironments being incredibly difficult to study in detail because of their minute size and delicate nature. As such, there is a real need for new technologies that can effectively construct these microenvironments within laboratories. This would enable a more precise understanding of human disease at a cellular basis and accelerate the development of new medications and treatments.

Holographic Optical Tweezers

We have developed a system that uses laser energy to grab individual cells and position them in three dimensions. This novel technique allows cells to be precisely manipulated, whilst preventing any physical cell damage. The basis of this system, a pixel chip called a spatial light modulator (SLM), conditions an expanded infrared laser to generate a hologram. The SLM chip integrates a grid of pixels that are individually controlled through a computer interface, enabling the generation of regions of relatively high laser intensity. The configured hologram then passes through a microscope objective that converts these regions into optical traps. While the basis of this technology already exists, we have used LabVIEW to apply the technique in an entirely new way.

Figure 2. Photographs and schematics show the LabVIEW-powered Holographic Tweezers

 

The software used to generate the holograms is hugely complicated and requires accurate control of the voltages applied to each SLM pixel. We developed a sophisticated LabVIEW application that hides this complex processing and instrument control behind an intuitive user interface. This is highly advantageous as scientists with diverse backgrounds, many of whom have no experience with computer programming, operate this instrument.

To trap microscopic objects, such as living stem cells, the operator simply uses a mouse to generate a trap in a desired region by double clicking on a live image feed relayed from a camera attached to a microscope. Once a cell is trapped, it can be quickly repositioned using a simple click-and-drag technique. The LabVIEW interface also supports incredibly precise, submicrometre positioning in x, y, z directions using numeric entry controls.

 

Figure 3. Using the LabVIEW interface to simultaneously reposition multiple stem cells.

 

Notably, the LabVIEW interface also empowers users to simultaneously reposition multiple types of living cells and/or synthetic objects. The software interface translates user-defined traps into SLM configurations to generate bespoke holograms. These complex 3D light patterns determine the position of each trap (see Figure 3).

Behind the scenes, our LabVIEW software delivers tight, coordinated control of a wide-range of scientific hardware including the SLM, camera, microscope stage and turret control. The advantage of using LabVIEW over any other platform is the ease at which we can control and integrate numerous devices that are obtained from a range of manufacturers.

In addition, the team of researchers who designed and developed this technology are from diverse backgrounds and had no formal training or experience with low-level programming. Unlike text-based languages, the graphical programming paradigm befits a typical scientific mindset and is easily visualised. We used LabVIEW to rapidly develop our sophisticated holographic tweezers software—something we simply could not have achieved with other development platforms.

Additionally, we used the Vision Development Module to quickly stream and process images from our microscope-mounted camera with minimal programming. We also used the module to easily apply visual overlays on the processed images to further improve the software’s usability by highlighting the applied optical traps and cell positions to the user.

The Evolution of the System

The carefully architected LabVIEW code allowed us to quickly extend the system to meet our evolving requirements. For example, we created an iPad app that directly interfaces with the LabVIEW control code. Not only does this help scientists monitor and interact with the test cells from anywhere within the university, but the iPad’s multitouch interface further simplified the simultaneous manipulation of multiple cells.

Global research collaboration is vital for the development of future medicines. A major limitation to this process are the geographical distances between collaborating laboratories, which confines access to emerging technologies, such as our holographic tweezers, to a single site. The system we have constructed can be interfaced remotely, so the instrument can be controlled from across the UK and even abroad. This significantly reduces travel costs and environmental impact, and allows collaborating scientists to be directly involved in gathering their data.

Figure 4. Remotely operating the holographic tweezers using an iPad has been hugely popular at academic conferences.

 

Because of the scalability of the LabVIEW code, we can customise the holographic tweezers system for a range of scientific applications, including in vitromodelling, biophysics, stem cell biology, and tissue engineering. With LabVIEW, subject matter experts, who may have limited programming knowledge, can implement software modifications to provide a high level of flexibility across diverse scientific disciplines.

In our case, a team of optical physicists at the University of Glasgow carried out the bulk of the programming for the study of physical forces down to a billionth of a meter. But, our team of researchers at the University of Nottingham’s School of Pharmacy was able to adapt the code for biological applications, like the study of cells. To facilitate this, NI provided certified training for a member of the Nottingham team. This helped us disseminate good programming practices to other members of the team and boosted our LabVIEW proficiency.

The Upshot of This New Technology

The NI platform simplified the development of our sophisticated software and allowed the precise control of diverse scientific instrumentation. We used LabVIEW to rapidly develop a new breed of instrument for studying stem cells at length scale, offering biological insights that were not previously achievable.

Figure 5. Examples of various cells have been built into defined structures using the holographic tweezers.

This new technology is being actively used to study diverse cellular microenvironments to deliver a more detailed understanding of the fundamental mechanisms that make us function. The knowledge gathered from these studies can help develop new, innovative medicines for the treatment of human disease. Also, when used in conjunction with other emerging technologies, these manipulated cells could aid the regrowth and repair of damaged tissue and organs, which carries the potential to improve the lives of millions of patients in the future.

 

Author Information:
Glen Kirkham
School of Pharmacy, University of Nottingham
University of Nottingham
NG7 2RD
United Kingdom
Tel: +44 (0)115 8232003
glen.kirkham@nottingham.ac.uk

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