The lab on a chip implementation of rapid and inexpensive instrumentation for medical diagnostics and the study of genomics, proteomics, and cellomics can significantly reduce the costs and increase the efficiency of medical diagnostics in the clinical setting, and potentially alleviate the global health care crisis. In order for doctors and physicians to be able to diagnose diseases at an early stage, while the disease may still be curable, it's necessary that they have access to a versatile platform which can rapidly and inexpensively analyze a wide panel of biomarkers, biomolecular indicators which signal the state of a disease. Of particular importance are genomic biomarkers, protein biomarkers, and cell biomarkers. Genomic biomarkers are important in giving an indication of a patient’s predisposition to certain diseases based on the patient’s DNA, and include nucleic acid biomarkers such as gene mutations, polymorphisms, and quantitative gene expression analysis. However, an understanding of the patient’s genome alone is insufficient for proper prediction of disease susceptibility due to the heterogeneous nature of diseases like cancer between populations. Knowledge of the proteome,1
which includes both quantifying the various protein structures and also the functional interactions between the proteins, can give a more comprehensive understanding of the state of the disease in a patient. Finally, the ability to detect various target cells such as tumor cells or bacterial cells in blood can be of immense use for early disease diagnosis. The comprehensive knowledge of the genome, the proteome, and the cellome for individual patients will provide the information necessary to make personalized medicine feasible across heterogeneous populations.
Current detection techniques require expensive labeling, long incubation times,2
and bulky optical equipment for fluorescence scanning, only allowing for the analysis of a limited panel of biomarkers in the clinical setting.3
It has become more apparent that a small number of markers are insufficient in properly diagnosing diseases across populations. Thus, the need for developing rapid inexpensive platforms which can be multiplexed to analyze a wide panel of biomarkers has become ever pressing.
Various attempts have been made at detection of cells, proteins, and DNA using electrical impedance based sensors, which are advantageous given that they lower preparation time and reagent costs due to elimination of fluorescent labeling.4
Label free detection of detection of changes in protein conformation has been reported recently using nanogap sensors 5
. Many of the above mentioned techniques, and other electrical biosensors presented to date require numerous washing steps while lacking the ability for real time detection. The biggest problem with most electrical impedance biosensors is achieving consistency in results. The use of coulter counters 6
makes possible the counting and sizing of particles in real time. The capture of target proteins on beads coated with probe molecules and the detection of their presence based on size changes has been demonstrated.7,8
However differentiation between two different proteins which may be similar in size is difficult.
We have developed a microfluidic platform capable of electrically detecting target cells 9
, target proteins,10
in less than an hour with at least the same sensitivity as the current techniques, while maintaining the selectivity which current electrical detection techniques do not have. With this type of integrated platform capable of detecting these three different types of markers, biomarker detection and discovery can be multiplexed to a level which the current techniques lack the capability thereof. In our previous work 9–11
, we have demonstrated the proof of concept for detection of these various biomarkers. In this paper, our intention is to discuss the performance limits of this device based on theoretical considerations and various experiments we have performed.