ABSTRACT
We report the design, fabrication and characterization of a microelectromechanical systems (MEMS) flow control device for gas chromatography (GC) with the capability of sustaining high-temperature environments. We further demonstrate the use of this new device in a novel MEMS chopper-modulated gas chromatography-electroantennography (MEMS-GC-EAG) system to identify specific volatile organic compounds (VOCs) at extremely low concentrations. The device integrates four pneumatically actuated microvalves constructed via thermocompression bonding of the polyimide membrane between two glass substrates with microstructures. The overall size of the device is 32 mm×32 mm, and it is packaged in a 50 mm×50 mm aluminum housing that provides access to the fluidic connections and allows thermal control. The characterization reveals that each microvalve in the flow control chip provides an ON to OFF ratio as high as 1000:1. The device can operate reliably for more than 1 million switching cycles at a working temperature of 300 °C. Using the MEMS-GC-EAG system, we demonstrate the successful detection of cis-11-hexadecenal with a concentration as low as 1 pg at a demodulation frequency of 2 Hz by using an antenna harvested from the male Helicoverpa Virescens moth. In addition, 1 µg of a green leafy volatile (GLV) is barely detected using the conventional GC-EAG, while MEMS-GC-EAG can readily detect the same amount of GLV, with an improvement in the signal-to-noise ratio (SNR) of ~22 times. We expect that the flow control device presented in this report will allow researchers to explore new applications and make new discoveries in entomology and other fields that require high-temperature flow control at the microscale.
ABSTRACT
BACKGROUND: The dissemination of circulating tumor cells (CTCs) that cause metastases in distant organs accounts for the majority of cancer-related deaths. CTCs have been established as a cancer biomarker of known prognostic value. The enrichment of viable CTCs for ex vivo analysis could further improve cancer diagnosis and guide treatment selection. We designed a new flexible micro spring array (FMSA) device for the enrichment of viable CTCs independent of antigen expression. METHODS: Unlike previous microfiltration devices, flexible structures at the micro scale minimize cell damage to preserve viability, while maximizing throughput to allow rapid enrichment directly from whole blood with no need for sample preprocessing. Device performance with respect to capture efficiency, enrichment against leukocytes, viability, and proliferability was characterized. CTCs and CTC microclusters were enriched from clinical samples obtained from breast, lung, and colorectal cancer patients. RESULTS: The FMSA device enriched tumor cells with 90% capture efficiency, higher than 10(4) enrichment, and better than 80% viability from 7.5-mL whole blood samples in <10 min on a 0.5-cm(2) device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples (approximately 76%) compared to 4 out of 18 (approximately 22%) detected with the commercial CellSearch® system. There was no incidence of clogging in over 100 tested fresh whole blood samples. CONCLUSIONS: The FMSA device provides a versatile platform capable of viable enrichment and analysis of CTCs from clinically relevant volumes of whole blood.
Subject(s)
Cell Separation/instrumentation , High-Throughput Screening Assays/instrumentation , Neoplastic Cells, Circulating , Tissue Array Analysis/instrumentation , Cell Count , Cell Culture Techniques , Cell Line, Tumor , Cell Proliferation , Cell Separation/methods , Cell Survival , Equipment Design , High-Throughput Screening Assays/methods , Humans , Leukocytes/cytology , Models, Biological , Neoplastic Cells, Circulating/pathology , Tissue Array Analysis/methodsABSTRACT
We demonstrated a high throughput versatile platform capable of isolating circulating tumor cells (CTCs) from clinically relevant volumes of blood while preserving their viability and ability to proliferate. The enrichment is based on the fact that CTCs are larger compared with normal blood cells. The incorporated system allows size-based separation of CTCs at the micro-scale, while taking advantage of a high throughput and rapid processing speed. Testing results of model systems using cell lines show that this device can enrich CTCs from 7.5 mL of whole blood samples with 90% capture efficiency, higher than 10(4) enrichment, and better than 80% viability in approximately ten minutes without any incidence of clogging.
