Ashish V. Jagtiani

A Micromachined High Throughput Coulter Counter for Bioparticle Detection and Counting

We describe a micromachined Coulter counter with multiple sensing microchannels for quantitative measurement of polymethacrylate particles and pollen. A unique design with sensing microelectrodes in the center of the microchannels is demonstrated. This design creates isolation resistances among channels, and thus circumvents the crosstalk caused by automatic electrical connection among microchannels. When implemented using microfluidic channels, this design is appropriate for the sensing of microscale particles in deionized water or in dilute electrolyte solution. Our design has multiple channels operating in parallel, but integrated with just one sample reservoir and one power source. The results with a four-channel device show that this device is capable of differentiating and counting micro polymethacrylate particles and Juniper pollen rapidly. Moreover, the device throughput is improved significantly in comparison to a single-channel device. The concept can be extended to a large number of sensing channels in a single chip for significant improvement in throughput.

Detection and counting of micro-scale particles and pollen using a multi-aperture Coulter counter

We demonstrate a high throughput, all-electronic Coulter-type sensor with four sensing microapertures to detect and count micro-scale particles. Four particle samples are utilized for this study: polymethacrylate particles 40 µm and 20 µm in diameter, Juniper Scopulorum (Rocky Mountain Juniper) pollen and Cottonwood pollen particles. The two types of pollen particles are roughly 20 µm in diameter. The particles are mixed with deionized water and forced to pass through the microapertures. Voltage pulses across all four apertures are recorded and analysed. Results demonstrate that the sensor can detect and count particles through its four sensing apertures simultaneously. Thus, the counting efficiency of the four-aperture sensor is approximately 300% higher than that of a single-channel Coulter counter, while maintaining the same accuracy, sensitivity and reliability. The counting efficiency can be improved further by integrating more sensing channels on a single micromachined chip. Results also demonstrate that the device can be used to differentiate between pollen and polymethacrylate particles; differentiation is based on a difference in surface charge for the two types of particles.

A label-free high throughput resistive-pulse sensor for simultaneous differentiation and measurement of multiple particle-laden analytes

We describe an all-electronic, label-free, resistive-pulse sensor that utilizes multiple microchannels for parallel detection, counting and differentiation of multiple biological particles simultaneously. Four particle solutions, including 20 µm and 40 µm polymethacrylate particles, Juniper Scopulorum (Rocky Mountain Juniper) pollen and Populus deltidoes (Eastern Cottonwood) pollen, were loaded to the four peripheral reservoirs, respectively, and were driven to the central reservoir through four microchannels, all operating simultaneously for particle detection and counting. Experiments demonstrated that this sensor was able to differentiate and count multiple particle solutions simultaneously through its four microchannels fabricated on polymer membranes. Thus the sensing throughput has been improved significantly in contrast to typical Coulter counters without sacrificing accuracy, sensitivity and reliability. Furthermore, the experimental results also proved the feasibility of differentiating various pollens from polymethacrylate microparticles with the multi-channel resistive-pulse sensor. The differentiation is based on difference in size and surface charge for the bioparticles, with no need for labeling of samples. Possible improvements and extensions to other biological particle detection are discussed.

A microfluidic multichannel resistive pulse sensor using frequency division multiplexing for high throughput counting of micro particles

In this work we demonstrate an on-chip multiplexed multichannel resistive pulse sensor (Coulter counter) for high throughput counting of microscale particles. The design, fabrication and testing of this device are presented. The high throughput counting is a result of using multiple parallel microfluidic channels to analyze the sample. Detection is achieved by using frequency division multiplexing; each microchannel is modulated with its own known and unique frequency, a combined measurement is made across a single pair of electrodes, and the measured signal is demodulated to determine the signal across each individual channel. Testing results using 30 µm polystyrene particles demonstrate that the throughput of the multiplexed device gets improved 300% over a single-channel device; this is achieved by simultaneously detecting particles through the devices four parallel channels. In addition, the ac modulation method used in this paper reduces the polarization effect on the microelectrodes, and thereby allows for measurement of the particle sizes with significantly reduced error. The multiplexed detection principle can be extended to a larger number of channels to further improve the throughput, without increasing the external detection electronics.

Capacitive Coulter Counting: Detection of Metal Wear Particles in Lubricant Using a Microfluidic Device

A microfluidic device based on the capacitance Coulter counting principle to detect metal debris particles in lubricant oil is presented. The device scans each individual metal debris particle as they pass through a microfluidic channel by monitoring the capacitance change. We first proved the feasibility of using the capacitance Coulter counting principle for detecting metal particles in a fluidic channel. Next, we tested the microfluidic device with aluminum abrasive particles ranging from 10 to 25 µm; the testing results show the microfluidic device is capable of detecting metal wear particles in low-conductive lubricant oil. The design concept demonstrated here can be extended to a device with multiple microchannels for rapid detection of metal wear particles in a large volume of lubricant oil.

A microfluidic Coulter counting device for metal wear detection in lubrication oil

We present the design, fabrication, and testing of a microfluidic device for metal wear detection in lubrication oils. The detection is based on the capacitance Coulter counting principle, that is, on the change in a microchannels capacitance caused by the presence of a metal particle in the microchannel. The testing of the microfluidic device using 10-25 microm aluminum particles has demonstrated the feasibility for detection and counting of microscale metal particles in low-conductive lubrication oils. This microfluidic device is promising for online oil debris detection by the use of multiple detection microfluidic channels.

A low-voltage droplet microgripper for micro-object manipulation

We present a low-voltage microgripper utilizing a liquid droplet to pick up and release micro-objects. Lifting force is generated by a liquid bridge formed between the gripper surface and an object. Electrowetting was used to dynamically change the capillary lifting forces and enable easy object release. The driving voltage was applied to a pair of coplanar interdigitated electrodes, eliminating the need for an electrode on top of the droplet and thus significantly facilitating object manipulation. A barium strontium titanate insulation layer was used to lower the driving voltage. Experiments indicated that the lifting forces can be as high as 213 µN at a driving voltage of 28 V. Experiments also demonstrated a low-voltage, low power consumption soft microgripper by picking up and releasing micro glass beads.

An impedimetric approach for accurate particle sizing using a microfluidic Coulter counter

In this paper, we present the design, impedimetric characterization and testing of a microfabricated Coulter counter for particle size measurement that uses a pair of thin film coplanar Au/Ti electrodes. An electrical equivalent circuit model of the designed device is analyzed. Accurate measurement of particle size was achieved by operating the device at a frequency for which the overall impedance is dominated by the channel resistance. A combination of design features, including the use of a pair of sensing electrodes with a surface area of 100 µm by 435 µm, a spacing of 1785 µm between the two sensing electrodes and a 350 µm long microchannel, ensures that this resistance dominates over a range of relatively low frequencies. The device was characterized for NaCl electrolyte solutions with different ionic concentrations ranging from 10−5 to 0.1 M. Results proved that the resistive behavior of the sensor occurs over a range of relatively low frequencies for all tested concentrations. The Coulter counter was then used to detect 30 µm polystyrene particles at a selected excitation frequency. Testing results demonstrated that the device can accurately measure particle sizes with small error. The design can be extended to ac Coulter counters with sub-micron sensing channels. Analysis of three designs of ac Coulter counters including sub-micron sensing channels using the electrical equivalent circuit model predicts that they can be operated at even lower frequencies, to accurately size nanoscale particles.

Wavelet transform-based methods for denoising of Coulter counter signals

A process based on discrete wavelet transforms is developed for denoising and baseline correction of measured signals from Coulter counters. Given signals from a particular Coulter counting experiment, which detect passage of particles through a fluid-filled microchannel, the process uses a cross-validation procedure to pick appropriate parameters for signal denoising; these parameters include the choice of the particular wavelet, the number of levels of decomposition, the threshold value and the threshold strategy. The process is demonstrated on simulated and experimental single channel data obtained from a particular multi-channel Coulter counter processing. For these example experimental signals from 20 µm polymethacrylate and Cottonwood/Eastern Deltoid pollen particles and the simulated signals, denoising is aimed at removing Gaussian white noise, 60 Hz power line interference and low frequency baseline drift. The process can be easily adapted for other Coulter counters and other sources of noise. Overall, wavelets are presented as a tool to aid in accurate detection of particles in Coulter counters.

Soft microgripping using ionic liquids for high temperature and vacuum applications

Aqueous droplet-based micro-gripper has been used for micro-assembly. However they cannot be used for high temperature and vacuum applications. Ionic liquids, organic salts that have a lower melting point temperature, appear suitable for droplet-based micro-gripping application in high temperature and vacuum environments because of their nonvolatility and thermal stability. In this paper, we demonstrated the use of ionic liquid as the operating liquid for micro-gripping applications in high temperatures (up to 110 °C) and vacuum (up to 24 inch Hg) environments. Electrowetting was utilized to dynamically change the contact angle of a 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) liquid bridge to control the capillary lifting forces. The lifting force generated by the liquid bridge was experimentally characterized. The range of capillary lifting forces can be adjusted by changing the liquid bridge height and droplet volume to pick up and release objects with different weights. The dynamic response of the BmimPF6 liquid bridge was also characterized.