Current work

General considerations

The use of microfluidic devices in developing countries poses a set of extremely challenging design criteria, including low cost, absence of trained workers, lack of electricity, poorly equipped laboratories, and transportation and storage in unrefrigerated conditions with rough handling.  In practice, not all of these constraints apply to all settings in developing countries. For example, in developing countries, different design criteria apply to centralized testing in a national laboratory, in a rural health clinic, and in a remote setting with no infrastructure.  Similarly, there exist subtle but important distinctions in the constraints. For ‘low cost’, the economics of centralized testing may allow for the purchase of a moderately priced or even expensive fixed instrument (tens of thousands of dollars), if the cost of disposables is kept sufficiently low. By contrast, remote point-of-care testing requires low cost in both the fixed instrument and the disposable (pennies).  These considerations are important in the design of every stage of a microfluidic device, from the choice of material and manufacturing process, all the way to disposal of the device after operation by the end user.

Proteins

Many diseases are characterized by changes in protein concentrations in a patient’s physiological fluids, including viral infections, bacterial infections, parasitic infections, and non-communicable diseases. Immunoassays are routinely used, with high sensitivity and specificity, to detect and quantitate protein markers. The most commonly used samples from the patient are whole blood, serum, and plasma, with less common samples being saliva, urine, feces, sperm, tears and sweat. Enzyme immunoassays, which comprise most protein tests, typically require the established infrastructure of centralized testing facilities to accomplish complex reagent handling and optical detection. Microfluidic devices may be developed that are less demanding in infrastructure. At least three important hurdles exist in the processes of miniaturization and automation: fluid actuation, mixing and fluid control, and signal detection.  All of these steps must all be made low-cost and portable.

Nucleic acids

Analysis of nucleic acids offers powerful diagnostic information that complement protein analysis of antigens and antibodies. For example, by analyzing conserved DNA or viral RNA sequences, PCR and RT-PCR can be used to specifically detect infectious diseases important in developing countries (such as HIV/AIDS, hepatitis B and C, and TB).  For HIV/AIDS, quantitative measurements of RNA levels provide information on the stage of diseases.  Nucleic acid detection can be very sensitive due to amplification, and specific due to the intrinsic complementarity of the base-pairing interactions. Nevertheless, the building of an integrated microfluidic device for detecting nucleic acids is typically more challenging than for proteins, due to at least three design issues: sample pre-treatment, signal amplification (PCR-based or isothermal amplification), and signal detection.

Cells

Analysis and counting of cells are important for diseases such as anaemia and hematology (via erythrocyte and complete blood counts), as well as for monitoring the progression of AIDS. Flow cytometry, the current standard for cell analysis and counting, can measure up to 10 or more cell properties and separate and isolate cells at rates up to 10 000 cells per second without loss of viability.  Since conventional flow cytometers are bulky, expensive, and mechanically complex, they are currently limited to well-financed centralized testing centers. Due mainly to the importance of counting CD4+ lymphocytes for monitoring the progression of AIDS, a number of initiatives have started to support the development of an inexpensive and compact device for cell counting for global health. With support from the Gates Foundation, Imperial College London is supporting the development of a simple, low-cost, and semiquantitative CD4+ lymphocyte-counting device that exhibits cut-offs at 200, 350, 500 cells per cubic mm with 10% coefficient of variation. Perhaps more so than simple membrane-based tests, LOC devices have the potential to meet these targets due to their increased versatility in design and enhanced analytical performance.

Others

A miniaturized microscope would aid in the diagnosis of malaria and other diseases.  One recent approach uses a microfluidics-based lensless imaging technique with a spatial resolution that is similar to a 40x objective lens of a compound microscope.  About 40 samples per minute could be sampled using this technique.

*Parts of this article are adapted from C. Chin, V. Linder, and S.K. Sia, "Lab-on-a-chip devices for global health", Lab on a Chip, 7:41-57 (2007).