There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Micro total analysis systems. Recent developments.

Optical tweezers (OT) have emerged as an essential tool for manipulating single biological cells and performing sophisticated biophysical/biomechanical characterizations. Distinct advantages of using tweezers for these characterizations include non-contact force for cell manipulation, force resolution as accurate as 100 aN and amiability to liquid medium environments. Their wide range of applications, such as transporting foreign materials into single cells, delivering cells to specific locations and sorting cells in microfluidic systems, are reviewed in this article. Recent developments of OT for nanomechanical characterization of various biological cells are discussed in terms of both their theoretical and experimental advancements. The future trends of employing OT in single cells, especially in stem cell delivery, tissue engineering and regenerative medicine, are prospected. More importantly, current limitations and future challenges of OT for these new paradigms are also highlighted in this review.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2008.0052

Optical tweezers for single cells

http://research.vuse.vanderbilt.edu/srdesign/2006/group19/Microfluidicstechnologyformanipulationandanalysisofbiologicalcells.pdf

Microfluidics technology for manipulation and analysis of biological cells

Mechanical forces play important roles in the regulation of various biological processes at the molecular and cellular level, such as gene expression, adhesion, migration, and cell fate, which are essential to the maintenance of tissue homeostasis. In this review, we discuss emerging bioengineered tools enabled by microscale technologies for studying the roles of mechanical forces in cell biology. In addition to traditional mechanobiology experimental techniques, we review recent advances of microelectromechanical systems (MEMS)-based approaches for cell mechanobiology and discuss how microengineered platforms can be used to generate in vivo–like micromechanical environment in in vitro settings for investigating cellular processes in normal and pathophysiological contexts. These capabilities also have significant implications for mechanical control of cell and tissue development and cell-based regenerative therapies.

/pdf/microengineered-platforms-for-cell-mechanobiology-403ur5va6e.pdf

Microengineered Platforms for Cell Mechanobiology

We have demonstrated the use of vertical cavity surface emitting lasers (VCSELs) for optical trapping and active manipulation of live biological cells and microspheres. We have experimentally verified that the Laguerre‐Gaussian laser mode output from the VCSEL functions just as well as the traditional Gaussian fundamental laser mode for optically trapping biological cells and may be preferable since the highest intensity of the Laguerre‐Gaussian mode is located at the outer ring of the optical aperture, which allows for stronger optical confinement to be obtained for a lower total power. Another advantage that VCSELs have over conventional gas and diode lasers is their ability to be manufactured in an array form. Using a 2 � 2 array of VCSELs, the simultaneous and independent transport of four human red blood cells is demonstrated indicating that much larger two-dimensional VCSEL arrays can be used as individually addressable optical tweezers in biological chips and systems. This parallel transport capability will have a significant impact in currently developing biochip array and assay technologies through the facilitation of the selection, relocation, and precision placement of cells. # 2002 Elsevier Science B.V. All rights reserved.

http://fleece.ucsd.edu/~sadik/EsenerReferences/083FlynnSensorsandActuators.pdf

Parallel transport of biological cells using individually addressable VCSEL arrays as optical tweezers

To study the chemotactic response of sperm to an egg and to characterize sperm motility, an annular laser trap based on axicons is designed, simulated with the ray-tracing tool, and implemented. The diameter of the trapping ring can be adjusted dynamically for a range of over 400 microm by simply translating one axicon along the optical axis. Trapping experiments with microspheres and dog sperm demonstrate the feasibility of the system, and the power requirement agrees with theoretical expectation. This new type of laser trapping could provide a prototype of a parallel, objective, and quantitative tool for animal fertility and biotropism study.

/pdf/dynamically-adjustable-annular-laser-trapping-based-on-33noswjhu1.pdf

Dynamically adjustable annular laser trapping based on axicons

Sperm motility is an important concept in fertility research To this end, single spot laser tweezers have been used to quantitatively analyze the motility of individual sperm However, this method is limited with throughput (single sperm per spot), lacks the ability of in-situ sorting based on motility and chemotaxis, requires high laser power (hundreds of milliWatts) and can not be used to dynamically monitor changes in sperm swimming behavior under the influence of a laser beam Here, we report a continuous 3-D ring-shaped laser trap which could be used for multi-level and high-throughput (tens to hundred sperm per ring) sperm sorting based on their motility and chemotaxis Under a laser power of only tens of milliWatts, human sperm with low to medium velocity are slowed down, stopped, or forced to change their trajectories to swim along the ring due to the optical gradient force in the radial direction This is the first demonstration of parallel sperm sorting based on motility with optical trapping technology In addition, by making the sperm swimming along the circumference of the ring, the effect of laser radiation, optical force and external obstacles on sperm energetics are investigated in a more gentle and quantitative way The application of this method could be extended to motility and bio-tropism studies of other self-propelled cells, such as algae and bacteria

/pdf/high-throughput-sorting-and-analysis-of-human-sperm-with-a-5aho7oa42a.pdf

High-throughput sorting and analysis of human sperm with a ring-shaped laser trap.

A microscope-integrated vertical cavity surface emitting laser (VCSEL) array trapping system capable of independent control, rotation, and batch processing of biological cells is developed and demonstrated. The trapping system is applied for manipulation of yeast cells and PC-12 cells. In our trapping system, a single VCSEL trap serves as a collector and distributor, while an array of VCSEL traps functions like a chip, enabling parallel processing of multiple objects. The trapping system here differs from earlier VCSEL tweezers set-ups in several ways, including (1) the optical traps are mobile with the addition of a static sample holder; and (2) both a single and an array of optical traps can be controlled independently by tilting mirrors at the conjugate planes of the objective back aperture, and their relative depth can be adjusted without losing trapping power. These enhancements provide an advantage for lab-on-a-chip devices that contain microfluidics, since the background flow resulting from moving the sample plane introduces complexity and uncertainty in the velocity and force analysis on microparticles or cells. In addition, independent control of traps can offer more flexibility in multi-target manipulation. Here, we address optical design considerations for keeping stable trapping performance while multiplexing. Potential improvements based on two independently controlled VCSEL arrays are discussed and related applications are investigated.

Manipulation of microspheres and biological cells with multiple agile VCSEL traps

In order to assess the capability to optically identify small marine microbes, both simulations and experiments of angular resolved light scattering (ARLS) were performed. After calibration with 30-nm vesicles characterized by a nearly constant scattering distribution for vertically polarized light (azimuthal angle=90 degrees ), ARLS from suspensions of three types of marine picoplankton (two prokaryotes and one eukaryote) in seawater was measured with a scattering device that consisted of an elliptical mirror, a rotating aperture, and a PMT. Scattered light was recorded with adequate signal-to-noise in the 40-140 degrees . Simulations modeled the cells as prolate spheroids with independently measured dimensions. For the prokaryotes, approximated as homogeneous spheroids, simulations were performed using the RM (Rayleigh-Mie) - I method, a hybrid of the Rayleigh-Debye approximation and the generalized Lorentz-Mie theory. For the picoeukaryote, an extended RM - I method was developed for a coated spheroid with different shell thickness distributions. The picoeukaryote was then modeled as a coated sphere with a spherical core. Good overall agreements were obtained between simulations and experiments. The distinctive scattering patterns of the different species hold promise for an identification system based on ARLS.

Bing Shao

Papers

Parallel transport of biological cells using individually addressable VCSEL arrays as optical tweezers

Dynamically adjustable annular laser trapping based on axicons

High-throughput sorting and analysis of human sperm with a ring-shaped laser trap.

Manipulation of microspheres and biological cells with multiple agile VCSEL traps

Angular resolved light scattering for discriminating among marine picoplankton: modeling and experimental measurements.