Ultrasensitive detection of bacteria using core-shell nanoparticles and a NMR-filter system
Original entry: Warren Lloyd Ung, APPHY 225, Fall 2009
"Ultrasensitive detection of bacteria using core-shell nanoparticles and a NMR-filter system"
Hakho Lee, Tae-Jong Yoon, and Ralph Weissleder.
Angewandte Chemie Internation Edition (2009).
Soft Matter Keywords
magnetic nanoparticles, biosensors, NMR, microfluidics
Lee et al have constructed a device, which can detect bacteria in biological samples, by targeting magnetic nanoparticles (MNP - shown in Figure 1) to attach to the bacteria of interest and detecting the resultant change in nuclear magnetic resonance (NMR) signal in solution. The NMR signal is sensed by a miniature NMR coil built into a microfluidic device (refer to Figure 2). In this particular study, they demonstrate the capacity for detecting small quantities of Mycobacterium tuberculosis in the context of a relevant biological context, sputum. Such a device could have an impact on the point of care diagnosis of infectious diseases, such as tuberculosis, which is still a major cause of death worldwide. In addition, the techniques introduced here are general enough that they could be applied to the detection of many different kinds of bacteria in a wide range of samples.
The detection of the bacterial pathogens, which cause various kinds of symptoms and diseases, is a powerful tool for physicians and other medical personnel for diagnosing patients. In many cases, an accurate and expedient diagnosis is the first step in allowing for effective treatments. Low-cost and miniature solutions such as this microfluidic device are especially promising for point-of-care applications in the developing world. The combination of simple device design, the ability to accurately detect low amounts of bacteria in biologically relevant samples, and specificity against a wide range of pathogens make this device well-suited to use in various environments.
Soft Matter Discussion
The device detailed here has two key elements, the magnetic nanoparticles and the microfluidic NMR device.
The magnetic nanoparticles can be selectively targeted to attach to any type of bacteria by coating the external surface with antibodies. As a result, these nanoparticles will automatically attach to any bacteria, which can be targeted using an antibody. This technique may also work for detecting other pathogens, such as viruses, if they are present in sufficient quantity. Currently, antibodies have been developed, which can specifically bind to almost any particular pathogen, meaning that just about any pathogen can be targeted using these nanoparticles.
The nanoparticles are fabricated by thermally decomposing Fe(CO)5. Thermal decomposition often takes place in a high-boiling point organic solution where small crystals of the material of interest are stabilized using surfactants . This technique leaves small, uniform particles of pure iron. The thin outer ferrite shell serves to passivate the nanoparticles, and is fabricated by controlled air-oxidation. As shown in Figure 1, the nanoparticles are very monodisperse. These nanoparticles function as NMR contrast agents due to their size and magnetization. When these nanoparticles are present in solution, they decrease the T2 relaxation time of the protons in nearby water molecules. Thus, by measuring the T2 relaxation time, it is possible to determine the concentration of bacteria in the volume. This study reports a threshold number of as few as 20 colony forming units detected in 1mL of sputum.
The device itself is essentially a large microfluidic chamber, which is surround by an NMR coil. The exit from the chamber is blocked by a membrane filter with a pore size of 100nm. Figure 3 on the left shows the operation of the device. The sample loaded into the chamber, and any bacteria are trapped by the filter. Nanoparticles added to the sample either become specifically attached to the target bacteria or are washed out of the chamber through the membrane filter. Once excess nanoparticles have been removed, NMR is carried out using the microcoil to determine whether the targeted bacteria was present in the original sample.