Miniaturized sensors point the way to better point-of-care analysis

Analytical science has traditionally been confined to the laboratory, which means that a sample collected in one location must often be transported a long distance before it can be tested and evaluated. In areas such as health care, forensic science, and homeland security, this can be lead to unacceptable delays, expense, and inconvenience, or accidental contamination or degradation. Ideally, analytical tests would be carried out where and when the sample is first collected, providing immediate feedback that could be used to decide on an appropriate course of action.

Existing in-the-field technologies tend to fall into one of two classes: inexpensive dipstick tests that provide crude information of the yes/no or high/medium/low variety, and high-end quantitative systems that consist of standard laboratory instrumentation in a portable format. The former are insufficiently quantitative for many applications, while the latter are often too expensive, cumbersome, or complicated. In practice, users need new, low-cost sensors that combine the simplicity of dipstick tests with the robust precision of laboratory-based instrumentation. To address this need, we combined microfluidics and plastic electronics, which brings inexpensive, quantitative in-the-field detection much closer to realization.

The microfluidics field uses techniques developed for silicon and plastic processing to engineer miniature devices on which chemical and biological processing takes place under precisely controlled conditions.¹ Typical microfluidic devices, or ‘chips,’ are fabricated by forming channels in silicon, glass, or plastic substrates, which are then sealed using a second substrate as lid (see Figure 1). All standard analytical processes—such as filtering, mixing, and separation—can be carried out in a microfluidic device, with dried assay reagents at different locations along the channel. These reagents dissolve instantly as the sample flows past. Using simple capillary action to draw fluid samples passively into the channels (eliminating the need for external pumps), it is possible to create fully integrated devices that carry out complete, self-contained chemical assays.

Figure 1. Typical microfluidic devices. (Reproduced from Wikipedia.)

The compactness of the microfluidic chip makes it attractive for in-the-field analysis, except for one significant obstacle. The last analysis step is transduction, which usually involves converting a chemical signal into an easily measured optical one. Unfortunately, this normally requires bulky off-chip light sources and photodetectors that preclude ready integration. We showed^1–5 that one promising option for creating integrated light sources and detectors is the use of wafer-thin (≪1μm) plastic electronic devices, which can be fabricated using low-cost solution or vacuum processing.⁶

A typical organic LED (OLED) comprises one or more layers of organic semiconductor sandwiched between two electrodes, one of which is transparent. The active layer emits light under electrical excitation and the devices may therefore be used as light sources: see Figure 2 (left). They may also be used in reverse as photodetectors, by illuminating the active layer to generate a measurable electrical current: see Figure 2 (right). We showed that organic photodetectors are extremely sensitive, exhibiting electrical characteristics that compare well with conventional silicon devices. For example, they can measure signals down to the picowatt level and maintain linearity over more than six orders of magnitude.¹

Figure 2. Structure of a typical organic LED (OLED) and photodetector.

In microfluidic applications, the OLED and photodetector are arranged in a face-on geometry on the top and bottom surfaces of the microfluidic chip with the channel in between (see Figure 3). Biolabels in the channel absorb photons from the OLED and may subsequently re-emit them as lower-energy photons. Depending on the type of optical filtering employed, the photodiode will detect the intensity of either the transmitted light from the OLED or the emitted light from the biolabel. Either way, it is possible to deduce the concentration of the biolabel (and hence the analyte). Using this configuration, we previously measured fluorescent beads down to the picomolar level, which is sufficient for a wide range of diagnostic tests.^1,2

Figure 3. Schematic of the integration of a microfluidic device with an OLED and photodetector for fluorescence detection.

Figure 4. A prototype device for immunoassay detection incorporates OLEDs and organic photodetectors and offers multiple analyte testing. (Reproduced with permission from Molecular Vision Ltd.)

The work horse of clinical diagnostics is the immunoassay—a biochemical test that quantitatively measures analyte concentration using the specific reaction of an antibody to its antigen. Molecular Vision, a spin-out company from Imperial College London, is developing immunoassay devices for cardiac analysis that aim to measure four cardiac markers—myoglobin, creatine kinase muscle and brain type (Ck-MB), troponin I, and pro-brain natriuretic peptide (pro-BNP)—using a single sample of blood (see Figure 4).^1,2 These prototype devices confirm the feasibility of using organic devices for sensitive diagnostic testing. However, they have the familiar ‘cartridge-plus-reader’ format, in which a disposable test device is plugged into a reusable reader that contains the optics and detection electronics. The real value of using organic devices will be realized in future work, where we aim to print organic light sources and photodetectors directly onto the microfluidic chip, creating fully integrated devices that remove the need for a separate reader.