Studying Cell Metabolism and Cell Interactions Using Microfluidic Devices Coupled with Mass Spectrometry

Microfluidic technology, also called “lab on a chip” (LOC), miniaturized the basic units of biological, chemical and medical laboratories using a chip with a size of only several square centimeters. This technology is rapidly developing in recent years. The manipulations of sample preparation, reaction, separation, and detection were integrated into micro-scale channels, in order to achieve a portable, automatic, rapid, and accurate analysis system. The concept of micro-total analysis systems (μTAS) was first defined by Manz [1] in 1990. During the last 30years, micro-fabricating techniques developed rapidly, as well as the separation and detection methods. Thus, the microfluidic devices fabrication was greatly improved. Micro-valves [2] and micro-reactors [3] were successfully integrated in the microfluidic devices, which provided the essential conditions for the integration and automation of microfluidic devices. As a fast developing analysis technique, μTAS was widely applied in various research fields, particularly in disease diagnosis, environment monitoring, immunoassays, and protein research [4].

Compare to the conventional chemistry and biology technologies, microfluidic device possesses the obvious advantages due to its small scale and high specific surface area. The microchannel, which has the similar dimension with cells, provides a powerful tool for the cell analysis. Mass spectrometry (MS), which is considered as a high sensitive detection method, is the best option for quantitative and qualitative analysis of chemical substance. The combination of these two techniques will play an important role in the study of exploring the physiological functions in organs or searching the essential unknown substance in cell reactions.

In order to further explore the law of life activities, the attentions should be focused on the cells, which are the basic unit of life. The essence of life activities is the cell behavior. In recent years, cell analysis is playing an important role in the research of intercellular substrate, cell secretion, and metabolites. It’s of major significance especially in the early diagnosis, treatment, and medicine screening of the major diseases, as well as the cell physiological and pathological processes.

In the real biological samples detection, the cells are mostly not from one single spice. In order to obtain the single spices for testing, and get the accurate biological, the requirement for sorting and separation different types of cells from complex samples needs to be met. Several approaches were developed to make miniaturized particle-sorting devices on a microfluidic platform. Dielectrophoretic forces [1], optical tweezing forces [2], hydrodynamic/hydrophoretic forces [3], magnetic forces [4], shear-induced lift forces [5], and gravity-driven forces [6] are introduced for cell sorting. However, many of these approaches are complicated, expensive, and require additional steps to label the particles to be sorted. Furthermore, the sorting efficiency of some of these methods is insufficient for diagnostic and therapeutic applications, such as polymerase chain reaction (PCR) [7, 8] or early cancer detection by circulating tumor cells (CTCs) [9].

The cell analysis is carried out with the intention to explore the physiological activities of living organisms, therefore obtain useful information on of disease prevention and treatment. The living organism is an organic entity, and each organ exists interdependently. Every single external stimulation would cause a chain reaction of the related organs, which induce the whole body’s quick response. The signal transmission between organs essentially is the transmission of certain substance, which was secreted by the cells belonging to the stimulation-caused organ. This compound searches for the receptor on the target tissue, and further transfers the signal. Through regulating the content and type of the secretions acting as the signal factors, the information is transferred to the receptor cells, and response is made by the living organism. Therefore, cell signaling is a part of a complex system of communication that governs basic cellular activities and coordinates cell actions, which requires for further studies. The lack of perceiving and correctly responding to their microenvironment is one possible reason for the loss of functional capabilities of development, tissue repair, and immunity as well as normal tissue homeostasis, which causes diseases such as cancer, autoimmunity, and diabetes.