On a chip

Abstract

The future of clinical and POC BioMEMS is very bright. With an increasing emphasis on the personalization of medicine and the rising costs of health care, early detection and diagnostics at the POC will be even more important. Early detection implies early intervention, resulting in the saving of lives and reducing overall spending. The potential impact of these technologies on the early diagnosis and management of both communicable and noncommunicable diseases is very high. Many grand challenges applications are possible, e.g., routine tests such as complete blood cell count on a chip that an individual can perform at home; detection of cardiac markers from blood after a perceived heart attack; detection of cancer markers such as exosomes, CTCs from blood, or protein biomarkers in serum; and detection of infectious agents such as virus and bacteria for public health. These applications are expected to result in new diagnostic assays for home, doctor's office, clinical laboratories, and various POC settings.

Figure 1

(a) Total deaths world-wide by broad cause group, World Bank income group and sex, 2008 (adapted from WHO, The Global Status Report on Non-communicable Diseases 2010[1], (b) Cause of death for all ages in 2007 in the USA. Note CLRD is Chronic Lower Respiratory Diseases [3].

Figure 2

Application and settings where clinical Point-of-Care (POC) can be used – ranging from personalized to hospital and ER settings

Figure 3

Sub-modules and functions that need to be performed inside a BioMEMS point-of-care Lab-on-chip device. The sample is processed and target analytes, molecules, or cells are captured via recognition elements. The target molecules or the source of the target, e.g. cells, are amplified. Finally the target is detected and identified using different possible approaches that could require a label or might be label-free.

Figure 4

Mining Blood for Cellular Information. Human blood contains a large variety of cells that are important for clinical diagnostic or monitoring of treatment. Separating target subpopulations from whole blood requires the handling of volumes of blood that can span more than three orders of magnitude.

Figure 5

(a) Mapping of CBC on a chip. Inset: A differential counter design with (1) and entrance counter, (2) capture chamber, and (3) exit counter. Scale bar is 1 cm. Adapted from [18], (b) An n improved differential module, which has a (1) red blood cell lysis region, (2) lysis quenching region, (3) entrance counter, (4) capture chamber, and (5) exit counter.

Figure 6

Precise measure of neutrophil motility in a microfluidic chip. Neutrophils that are injected in the microfluidic device in the main channel, migrate laterally to enter an array of small channels filled with chemoattractant towards which they move at uniform speed.

Figure 7

(a) Optical micrograph of a microfluidic biochip for bacterial culture and identification [14,26], (b) SEM images of the channels and wells inside the chip, and (c) concept schematic of a cartridge housing the chip along with reagents needed to perform biomolecular assays.

Figure 8

CTCs have a broad range of applications in the management of cancer patients. The two microfluidic technologies developed in the Toner group are called CTC-Chip and are based on chemical capture of CTCs from whole blood. The original work was based on increasing the interaction of CTCs with microposts that are chemically modified with an antibody to bind to CTCs and not to leukocytes or blood cells. The second generation technology replaced the microposts with herringbone pattern only on the top surface to achieve gently mixing of blood as it flows through the chip in order to bring CTCs in contact with the antibody coated surfaces of the CTC-Chip. The key structures in both cases vary between 20 to 50 microns. The details of the chip geometry are given elsewhere [29-32].