Analyst Blog

When a drop is applied to a surface and dries, a number of factors control the formation of the dried drop. Essentially as the fluid or solvent evaporates, capillary flow transports molecules to the contact line of the drop with the surface and the drop dries as a ring with components coarsely separated, like a coffee ring.

Drop deposition of biofluids is being investigated worldwide as a possible diagnostic tool. However, the parameters that affect the formation of the biofluids coffee ring are not fully understood and this is a barrier that needs to be overcome in order to realise the clinical potential of drop deposited biofluids. Drop deposition is particularly well suited for examining low abundance biofluids such as tears and synovial fluids but is also widely investigated for blood plasma and serum.

A team of US researchers, based at the University of Michigan, have recently published a HOT article characterising biofluids prepared by drop deposition. The researchers studied two model biofluids, blood plasma and synovial fluid, when deposited onto slightly hydrophilic substrates with a contact angle of 50 – 90 degrees. The researchers showed that under most circumstances the model biofluids followed the piling model, as suggested by Deegan et al. and that an increased understanding of the time-dependent rheology and intermolecular forces that occur during evaporation would provide a better approximation. Importantly, from molecular analysis of the drop via Raman spectroscopy, that whilst the morphology of the dried drop changed the chemical composition and molecular structure of the dried proteins within the outer ring were unaffected.

Recent surveys from Allergy UK have shown that the rates of allergy are increasing throughout the world, affecting up to 30-35 % of people at some point during their lives, in some cases with fatal consequences. In vitro testing of specific Immunoglobin E (IgE) reactivities is thought to be able to significantly improve diagnostic accuracy and management in primary care. IgE plays a significant role in allergic conditions. Current methods for the sensitive and accurate detection of specific IgE reactivities are expensive; require significant sample preparation and investment in equipment. There is a need to provide a cheap, rapid, sensitive and specific test for IgE reactivities.

In a recent HOT article, a group of Swedish and Dutch Scientists describe a paper based lateral flow microarray for rapid allergy diagnostics. One of the authors, Jesper Gantelius of the Science for Life Laboratory, highlights “There is a rapid worldwide increase in atopic disorders and asthma without a clear understanding of the underlying cause. We have developed a paper-based microarray assay that could be used to rapidly and cost-efficiently evaluate a large number of specific IgE sensitisation’s in a primary care setting. The device may come to aid doctors in the personalised management of individual patients, as well as allow public health bodies to gain a better insight into the rapid increase of allergy-related conditions.”

The group, led by Prof. Helene Andersson Svahn, describe exciting research that was able to detect the responses of 15 specific IgE responses from 35 clinical serum samples with an inter-assay variability of 12 % revealing good general agreement with a current multiplexed array-based methodology. Interestingly this process is fully scalable and all that is required for data feedback is a consumer-grade flatbed scanner or smartphone camera enabling point-of-care diagnostics.

A lateral flow paper microarray for rapid allergy point of care diagnostics

Thiruppathiraja Chinnasamy, Loes I. Segerink, Mats Nystrand, Jesper Gantelius and Helene Andersson Svahn

Liquid chromatography using nanofluidic chip and DIC-TLM

The field of separation science has been continually evolving to enable the separation of smaller volumes. This interdisciplinary field has required developments in capillary electrophoresis, microfluidics and new detection technologies such as plasmonic sensing and thermal lensing. 

Researchers from the Department of Applied Chemistry, University of Tokyo lead by Prof. Kitamori have shown the ability to perform femtolitre (1 x 10^-15) separation and detection of nonfluorescent samples in a nanofluidic device. Using an extended nanofluidic device the researchers were able to separate and detect nonfluorescent molecules for the first time. Previous detection methodologies relied mainly on laser-induced fluorescence. 

The researchers showed the ability of nanofluidic separation science combined with differential interference contrast thermal lens microscopy (DIC-TLM) to enable detection of 370 molecules in a 2.3 μm wide by 350 nm deep nanochannel with a separation efficiency of 150,000 plates/m. DIC-TLM is thermal lens microscopy with an increased detection limit by realising background-free photodetection using differential interference contrast. 

Amazingly the injection volume and number of molecules were estimate to be 21 fL (1 x 10^-15) and 250 zmol at the limit of detection. This limit of detection provides separation of a sample 8 orders of magnitude smaller that that possible with high-performance liquid chromatography. This injection volume is much smaller than a single cell and detection limit is similar to the number of typical protein molecules in a single cells. Providing a promising tool for single cell research. 

To read more about this research download the HOT article which is free to access until April 5^th 

Femtoliter-Scale Separation and Sensitive Detection of Nonfluorescent Samples in an Extended-Nano Fluidic Device
Hisashi Shimizu, Kazuma Mawatari and Takehiko Kitamori 
Analyst, 2014, Accepted Manuscript