OVERVIEW

Small, low-cost, robust, reliable, and sensitive sensors are needed to enable the realization of practical and economical sensor networks. Although there are a large number measurands that are of interest for sensor-network applications (e.g., seismic, temperature, light, sound, magnetic, chemical, etc.), appropriate commercial sensors exist for many of these measurands. However, one prominent exception is the fact that appropriate chemical sensors are not available. It is for this reason that the sensor technology effort within CENS is researching the design, fabrication, and implementation of chemical sensors that have the specifications needed for sensor networks.

In order to have a targeted effort to develop chemical sensors for sensor networks, we have focused on one sensor-network application, namely monitoring soil contamination / habitat monitoring. To model the flow of contaminants in soil, miniaturized lab-based soil systems (i.e., designed on the scale of meters) are first used to simulate real-world macroscopic field tests. These lab-based test systems need an array of miniaturized chemical sensors to accurately monitor the flow of contaminants in the model. Microsensors developed for this application will first be used in the lab-based system that has a controlled environment. Once the sensors have the robustness needed they will be used for field tests. To further focus and simplify the initial sensor technology development, the specific chemical contaminant compound that will be monitored is nitrate.

VISION STATEMENT

For biochemical analysis, separation is usually performed prior to detection, which essentially eliminates the need for highly specific sensing. High Performance Liquid Chromatography (HPLC) is one of the most powerful, versatile, and widely used separation techniques. It allows separation, identification, purification, and/or quantification of the chemical compounds in complex mixtures. By miniaturizing HPLC system onto a chip, significantly lower sample and solvent requirements, higher mass sensitivity, and lower cost can be achieved. With down-sized HPLC column dimension (ID), the separation performance is unaffected, while the maximum concentration of each separated peak scales inversely with column ID square, hence favoring scaling. This work is then to develop portable HPLC systems that can be used for field tests and/or networked sensing, which is impossible or impractical for conventional desktop HPLC systems.

SYSTEMS / EXPERIMENTS

Description of Experiments and Systems for the Development of Micromachined Liquid Chromatography Systems

The first step in the research of microscale liquid-chromatography systems is the microfabrication of their components. In our research it was found that Parylene is the essential building material for the proposed micro-chromatography system, since it uses Parylene as the structural material and photoresist as the main sacrificial material. Parylene is a crystalline polymer thin film, which can be deposited at room temperature. We have set up a Parylene deposition technique that is compatible with MEMS processes. Figure 1 shows a schematic drawing of the Parylene deposition system. Moreover, we have proven that various fluidic components, like micro valves, flow sensors and shear stress sensors can be fabricated using Parylene technique. And now we are putting them together to make a partially integrated chromatography system for detecting common ions in water. For testing of the chips, syringe pumps and manual valves are used to provide fluidic support for the chip. The syringe pump can easily provide flow rates needed for microfluidic chip, which usually ranges from nl/min to 1ul/min. Probe station is used to monitor/see the chips.

The system used in the Liquid Chromatography-Electrospray Ionization (LC-ESI) experiments is an Agilent 1100 LC-MS system (Figure 2). The original housing for the electrospray interfacing is removed to allow nozzle on the chip to access the electro-spray inlet. Electrospray voltage is applied to the flow path by adding a tee connector, in which one port is a gold electrode. The electrospray voltage is about 1200 volts.

ACCOMPLISHMENTS

We have successfully developed the first integrated Ion Liquid Chromatography System On-a-Chip for multiple-ion separation and sensing, and an integrated LC-ESI (Electrospray Ionization) chip for protein and peptide separation and sensing using mass spectrometer. The two chips are both made using parylene microfluidics technology. 

(a) The Ion Liquid Chromatography (ILC) chip is integrated with on-chip bead-packed separation column, frits/filters, cross-channel sample injection structure, and conductivity detector. The microchip is integrated on silicon wafer using parylene technology, with a single CMOS-compatible batch fabrication. A novel self-aligned trench-anchoring technique is developed to dramatically increase the pressure compatibility of parylene microfluidic devices from about 30psi to at least 800psi. The separation column is 8mm-long, 100µm-wide, 25µm-high, and packed with 7µm-diameter anion-exchange beads using conventional slurry technique. It is found experimentally that the on-chip packed micro-column has higher permeability than conventional ones. On-chip 4.5nL sample injection, pressure-driven LC separation, and conductivity detection of seven-anion mixture (F^-, Cl^-, NO₂^-, Br^-, NO₃^-, PO₄^-3, SO₄^-2) with concentrations from 12.5ppm to 25ppm has been successfully demonstrated (Figure 1). All peaks are resolved in about 90 seconds, demonstrating a fast separation. The peaks are sharp because of the small dimension and minimized dead volume of the chip-based LC system. The detection limit is estimated to be around 1ppm for the anions, which is essentially limited by the non-suppressed background signal and conductivity readout electronics.

Figure 1. On-chip ion liquid chromatography separation result of seven common anions.

(b) We have also developed a complete LC-ESI/MS Chip, integrated with high pressure Liquid Chromatography (LC) separation column, frit, and Electro-Spray Ionization (ESI) nozzle (Figure 2). The chip is microfabricated on silicon wafer with a batch-fabrication process compatible with Integrated Circuits (IC) technology. The separation column is 6.5 cm-long, 100 µm-wide and 25 µm-high with rounded cross-sections, and is packed with 5 µm C18 porous silica beads with conventional slurry technique. The freestanding ESI nozzle is 600 µm-long with a 15 µm-wide, 3 µm-high opening. The on-chip packed column is found to have higher permeability than conventional LC columns. On-chip reverse-phase LC separation of Cytochrome C digest coupled with on-line mass spectrometer (MS) detection is demonstrated (Figure 3).

Figure 2. Device pictures of the integrated LC-ESI chip.

Figure 3. Separation result of digested cytochrome c using on-chip separation and ESI coupling to a mass spectrometer.

FUTURE Work

Eying for System Integration

Since both of these systems are fabricated with parylene microfluidic technology using compatible processes, their functions can be combined and expanded to provide a more complete on-chip biochemical processing and analysis system including sample preparation, extraction, enhancement, and detection. The proposed chip will start with raw sample and perform on-chip filtering through a filter/absorption column to remove most unwanted impurities. Then a separation is performed to extracted target samples. The sample peak can be further enhanced through an enhancement column where the sample concentration is increased. Finally the sample plug can be analyzed with various on-chip and/or off-chip detectors, such conductivity, UV absorbance, laser-induced fluorescence, and mass spectrometry.

PEOPLE

Faculty:

Prof. Yu-Chong Tai (Caltech)

Graduate Student:

Qing He

Undergraduate Student:

Carl Chin
Cesar Del Solar