P. H. Yap

Refractive index measurement of single living cells using on-chip Fabry-Pérot cavity

This letter reports the measurement of single living cells’ refractive index (RI) using an on-chip fiber-based Fabry-Perot cavity by a differential method. In experiment a single cell is captured into the cavity, then the spectral shift in response to the buffer change and the cell presence/absence can be used to determine the cell’s RI and size. Experiment on kidney cancer cells measures an effective RI of 1.399 at 0.1% accuracy. Compared with other approaches, the differential method eliminates uncertain factors and thus ensures high accuracy. The microchip facilitates automatic detection and makes it promising for label-free drug screening.

Determination of single living cell’s dry/water mass using optofluidic chip

This paper presents an interferometric method for measuring the dry/wet mass of a single living cell using an optofluidic chip. It consists of the fiber Mach-Zehnder interferometer and the fiber-optical trap, both of which are integrated onto a single chip. In experiment, a single living cell is captured by the fiber-optical trap, and then the cell’s refractive index and diameter are simultaneously determined by the spectral shift in response to the buffer modulation. Hence, both cell dry and water masses can be calculated with a precision higher than 5%.

An optofluidic volume refractometer using Fabry–Pérot resonator with tunable liquid microlenses

This letter reports the development of an optofluidic Fabry-Pérot (FP) resonator, which consists of a microcavity and a pair of liquid microlenses. The microcavity forms part of the microchannel to facilitate sample injection. The liquid microlenses are used for efficient light coupling from the optical fiber to the microcavity. The liquid microlens collimates the diverging light from the optical fiber into the FP cavity, which provides real-time tuning to obtain the highest possible finesse up to 18.79. In volume refractive index measurement, a sensitivity of 960 nm per refractive index unit (RIU) and a detection range of 0.043 RIU are achieved.

Cell compressibility studies utilizing noncontact hydrostatic pressure measurements on single living cells in a microchamber

A micro-optical-fluidic system (MOFS), which integrates a force generating device and an optical detector, is designed to measure the bulk modulus of a single living cell in real time under a controlled hydrostatic pressure. In this design, the accuracy of the bulk modulus measurement is improved because neither the force generating device nor the optical detector needs to be in contact with the cells. The MOFS device has been used to investigate the mechanotransduction of THP-1 human acute monocytic leukemia cells and the effects of the toxin lipopolysaccharide and colchicine on various properties of these cells.

Determination of refractive index for single living cell using integrated biochip

This paper reports a novel method for measuring the effective refractive index (RI) of single living cell with a small integrated chip. This microchip is able to determine the RI of living cell in real time without extra requirements of fluorescence labeling and chemical treatments, offering low cost and high accuracy meanwhile. It might provide an efficient approach for diseases or cancer diagnosis. The measurement system integrates laser diode, microlenses, and microfluidic channels onto a monolithic chip. In the experiments, two standard polystyrene beads with nominal RIs are, employed to calibrate the system and five types of cancerous cells are subsequently measured. The results indicate that the RI of the tested cells ranges from 1.392 to 1.401, which is larger than typical value 1.35-1.37 for normal cells.

Nanometer-precision linear sorting with synchronized optofluidic dual barriers

Researchers explore loosely overdamped system with extreme low stiffness for nanoparticle sorting with nanometer precision. The past two decades have witnessed the revolutionary development of optical trapping of nanoparticles, most of which deal with trapping stiffness larger than 10−8 N/m. In this conventional regime, however, it remains a formidable challenge to sort out sub–50-nm nanoparticles with single-nanometer precision, isolating us from a rich flatland with advanced applications of micromanipulation. With an insightfully established roadmap of damping, the synchronization between optical force and flow drag force can be coordinated to attempt the loosely overdamped realm (stiffness, 10−10 to 10−8 N/m), which has been challenging. This paper intuitively demonstrates the remarkable functionality to sort out single gold nanoparticles with radii ranging from 30 to 50 nm, as well as 100- and 150-nm polystyrene nanoparticles, with single nanometer precision. The quasi-Bessel optical profile and the loosely overdamped potential wells in the microchannel enable those aforementioned nanoparticles to be separated, positioned, and microscopically oscillated. This work reveals an unprecedentedly meaningful damping scenario that enriches our fundamental understanding of particle kinetics in intriguing optical systems, and offers new opportunities for tumor targeting, intracellular imaging, and sorting small particles such as viruses and DNA.

Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement

Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer’s theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.Optical trapping is a versatile tool for biomedical applications. Here, the authors use an optofluidic lattice to achieve controllable multi-particle hopping and demonstrate single-bacteria-level screening and measurement of binding efficiency of biological binding agents through particle-enabled bacteria hopping.

A micro-optic-fluidic spectrometer with integrated 3D liquid-liquid waveguide

A micro-optic-fluidic spectrometer is demonstrated for the fluorescence detection of moving particles in a microfluidic chip. The object is excited within an integrated 3D liquid-liquid waveguide and its fluorescence spectrum is real-time recorded with resolution of 10 nm. Three different types of fluorescence beads were tested and distinguished by this spectrometer which holds a promising new concept of the multi-color fluorescence detection in microchip flow cytometry.

Differential Mach-Zehnder Interferometer for Simultaneously Determining Size and Refractive Index of Living Cells

This paper represents a differential method for simultaneously measuring the refractive index (RI) and the size of single living cells using the fiber-based Mach-Zehnder interferometer and optical trapping; both are integrated onto an optofluidic chip. In experiment, a living cancerous cell MDCK is trapped by 45-mW laser light and then the cells refractive index and diameter are simultaneously determined by the spectral shift in response to the buffer modulation and cell presence/absence. The measured cell has a size of 15.1 mum and a RI of 1.397 at an accuracy of 0.1%.

Single Living Cell Refractometry using FBG-Based Resonant Cavity

This paper reports a single cell refractometer consists of FBG fiber-based resonant cavity by employing buffer modulation method. In this biophotonic chip, single cell is trapped optically in the cavity, and the transmission spectral shifts due to the change of surrounding buffer, without and with cell, are used to determine the cells refractive index (Rl) and size. The measurement shows that MDCK cell has an effective Rl of 1.383 at a precision of 0.1%. Moreover, the measurement method with optical trapping eliminates uncertain factors and prevents cell damage. The chip is promising for label-free cell measurement and further cell analysis.