Levent Yobas

Microdevice for the isolation and enumeration of cancer cells from blood

Cancer metastasis is the main attribute to cancer-related deaths. Furthermore, clinical reports have shown a strong correlation between the disease development and number of circulating tumor cells (CTCs) in the peripheral blood of cancer patients. Here, we present a label-free microdevice capable of isolating cancer cells from whole blood via their distinctively different physical properties such as deformability and size. The isolation efficiency is at least 80% for tests performed on breast and colon cancer cells. Viable isolated cells are also obtained which may give further insights to the understanding of the metastatic process. Contrasting with conventional biochemical techniques, the uniqueness of this microdevice lies in the mechanistic and efficient means of isolating viable cancer cells in blood. The microdevice has the potential to be used for routine monitoring of cancer development and cancer therapy in a clinical setting.

High-performance flow-focusing geometry for spontaneous generation of monodispersed droplets

A high-performance flow-focusing geometry for spontaneous generation of monodispersed droplets is demonstrated. In this geometry, a two-phase flow is forced through a circular orifice integrated inside a silicon-based microchannel. The orifice with its cusp-like edge exerts a ring of maximized stress around the flow and ensures controlled breakup of droplets for a wide range of flow rates, forming highly periodic and reproducible dispersions. The droplet generation can be remarkably rapid, exceeding 10(4) s(-1) for water-in-oil droplets and reaching 10(3) s(-1) for oil-in-water droplets, being largely controlled by flow rate of the continuous phase. The droplet diameter and generation frequency are compared against a quasi-equilibrium model based on the critical Capillary number. The droplets are obtained despite the low Capillary number, below the critical value identified by the ratio of viscosities between the two phases and simple shear-flow.

Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients

The isolation of circulating tumor cells (CTCs) using microfluidics is attractive as the flow conditions can be accurately manipulated to achieve an efficient separation. CTCs are rare events within the peripheral blood of metastatic cancer patients which makes them hard to detect. The presence of CTCs is likely to indicate the severity of the disease and increasing evidences show its use for prognostic and treatment monitoring purposes. We demonstrated an effective separation using a microfluidic device to utilize the unique differences in size and deformability of cancer cells to blood cells. Using physical structures placed in the path of blood specimens in a microchannel, CTCs which are generally larger and stiffer are retained while most blood constituents are removed. The placements of the structures are optimized by computational analysis to enhance the isolation efficiency. With blood specimens from metastatic lung cancer patients, we confirmed the successful detection of CTCs. The operations for processing blood are straightforward and permit multiplexing of the microdevices to concurrently work with different samples. The microfluidic device is optically transparent which makes it simple to be integrated to existing laboratory microscopes and immunofluorescence staining can be done in situ to distinguish cancer cells from hematopoietic cells. This also minimizes the use of expensive staining reagents, given the small size of the microdevice. Identification of CTCs will aid in the detection of malignancy and disease stage as well as understanding the phenotypic and genotypic expressions of cancer cells.

Thermally mediated droplet formation in microchannels

Precise dispensing of microdroplets is an important process for droplet-based microfluidics. The dropletformation by shear force between two immiscible fluids depends on their flow rates, the viscosities, and the interfacial tension. In this letter, the authors report the use of integrated microheater and temperature sensor for controlling the dropletformation process. The technique exploits the dependency on temperature of viscosities and interfacial tension. Using a relatively low heating temperature ranging from 25 to 70 ° C , the droplet diameter can be adjusted to over two times of its original value. The relatively low temperature range makes sure that this concept is applicable for droplets containing biological samples.

A novel integrable microvalve for refreshable Braille display system

We introduce a novel integrable and electrostatic microvalve for the purpose of enabling a pneumatic refreshable Braille display system (RBDS). Physical design parameters of the microvalve such as orifice size, beam length, number of beams and beam profile are experimentally explored and found promising for use with the RBDS. Particularly, one design with an orifice of 70 /spl mu/m/spl times/70 /spl mu/m, beam length of 665 /spl mu/m, and beam count of 20 is electrostatically closed against a differential pressure of 82.7 kPa with an applied voltage of 68 V-rms. Also introduced is a steady-state mechanical model of the microvalve established on a coupled solution of fluid and solid domains. The model and experimental test results have been used to calculate the unknown discharge coefficient, elastic deflection, and entrance pressure. The model reveals that some of the designs have remarkably low discharge coefficient and entrance pressure, implying that pressure loss occurs mostly through and around the inlet port even at fairly large supply pressures. Experimental observations concerning the practical use of the microvalve are discussed.

Digital microfluidics : Droplet based logic gates

The authors present microfluidic logic gates based on two-phase flows at low Reynold’s number. The presence and the absence of a dispersed phase liquid (slug) in a continuous phase liquid represent 1 and 0, respectively. The working principle of these devices is based on the change in hydrodynamic resistance for a channel containing droplets. Logical operations including AND, OR, and NOT are demonstrated, and may pave the way for microfludic system automation and computation.

Formation and manipulation of ferrofluid droplets at a microfluidic T-junction

This paper reports the formation and manipulation of ferrofluid droplets at a microfluidic T-junction in the presence of a permanent magnetic field. A small circular permanent magnet with a diameter of 3 mm is used to control the size of the ferrofluid droplets within a microfluidic device. In the absence of a magnetic field, the size of the ferrofluid droplets decreases linearly with the increase of the flow rate of the continuous phase. In the presence of a magnetic field, the size of the droplets depends on the magnetic field strength, magnetic field gradient and the magnetization of the ferrofluid. The magnetic field strength is adjusted in our experiment by the location of the magnet. The induced attractive magnetic force affects the droplet formation process leading to the change in the size of the formed droplets. Experimental observation also shows that the relative change in the size of the droplet depends on the flow rate of the continuous phase. Furthermore, the paper compares the evolving shape of the ferrofluid droplet during the formation process with and without the magnetic field.

Thermally mediated breakup of drops in microchannels

The authors used thermally induced surface tension gradients to manipulate aqueous droplets in microchannels. Control of the droplet breakup process was demonstrated. Droplet sorting can be achieved with temperatures above a critical value. Numerical simulation using a two-dimensional model agrees qualitatively well with the experimental results. The used control temperature of less than 55°C shows that this active control concept is suitable for biochemical applications. Thermal control promises to be a simple and effective manipulation method for droplet-based lab on a chip.

A novel bulk micromachined electrostatic microvalve with a curved-compliant structure applicable for a pneumatic tactile display

Recent success of microelectromechanical systems (MEMS) in projection displays have raised similar expectation for an efficient, low power, affordable, full-page and pneumatic tactile display. Such design has not been achieved by the conventional technology but could bring significant improvement to current refreshable Braille displays. This paper demonstrates a novel bulk-micromachined electrostatic microvalve suitable for a pneumatic tactile display. The microvalve, a silicon perforated diaphragm juxtaposed to a silicon inlet orifice, requires relatively low closing voltage against a large supply differential pressure and flow rate, i.e., 72.9 V-rms for 19.3 kPa and 85 mi/min. Such an attractive characteristic is due to its unique curved-compliant structure that has, unlike other electrostatic microvalves, no tolerance for any initial air gap between its electrodes. As a design tool, a mechanical model of the microvalve is introduced based on the lubrication theory and large plate deflection theory. The model is established on a steady-state coupled field problem of fluid-solid mechanics. Reynolds and von-Karman equations were simultaneously solved for the microvalve geometry by finite difference approximation and double Fourier series expansion. The results of the model and experiments are compared and found to be in good agreement with a relative error less than 10%.

Thermally controlled droplet formation in flow focusing geometry : formation regimes and effect of nanoparticle suspension

This paper reports experimental investigations on the droplet formation of deionized water and a nanofluid in a heat-induced microfluidic flow focusing device. Besides the effect of temperature, the effects of nanoparticle suspension (nanofluid) and the flow rate of aqueous fluid on the droplet formation and size manipulation were studied. At constant flow rates of the two liquids, three different droplet breakup regimes were observed and their transition capillary numbers as well as temperatures were identified. The heat generated by an integrated microheater changes the droplet formation process. Increasing the temperature enlarges the size of the droplets significantly. These results also demonstrate that the titanium oxide (15 nm)/deionized water-based nanofluid exhibits similar characteristics in droplet formation at different temperatures and any small change in the flow rate of this nanofluid has little impact on the size of the droplets formed in a flow focusing geometry.