Zero-cost diagnostics on papers

George Whitesides is a Chemistry professor at Harvard University, and his recent work seems to have the potential to change the way diagnostic medicine works. Dr. Whitesides and his team have recently developed a prototype “paper chip” that is capable of diagnosing multiple disease simply with the application of a blood drop.

Here is the talk given by Prof. Whitesides on paper diagnostics:



Here are the papers on paper diagnostics from the same research group:

Patterned Paper as a Platform for Inexpensive, Low-Volume, Portable Bioassays†, Angew Chem. 2007

Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis, Anal Chem, 2008

Three-dimensional microfluidic devices fabricated in layered paper and tape, PNAS, 2008

FLASH: A rapid method for prototyping paper-based microfluidic devices, Lab Chip, 2008

Understanding Wax Printing: A Simple Micropatterning Process for Paper-Based Microfluidics, Anal Chem, 2009

Paper-supported 3D cell culture for tissue-based bioassays, PNAS, 2009

Diagnostics for the Developing World: Microfluidic Paper-Based Analytical Devices, Anal Chem, 2009

Electrochemical sensing in paper-based microfluidic devices, Lab Chip, 2010

Programmable diagnostic devices made from paper and tape, Lab Chip, 2010

Paper‐Based ELISA, Angew Chem, 2010

And more and more publications over the last 3 years have been published by Prof. Whitesides' research group. Known with his contibutions to microfludics, Prof. Whitesides is opening up a field on paper based diagnositics...

High speed Atomic Force Microscopy unveils the steps of Myosin V

In Nature's October issue, the direct visualization of Myosin V motor proteins has been reported by using high-speed atomic force microscopy. The high-resolution movies not only provide corroborative ‘visual evidence’ for previously speculated or demonstrated molecular behaviours, including lever-arm swing, but also reveal more detailed behaviours of the molecules, leading to a comprehensive understanding of the motor mechanism.

Here is the recent report in Nature:
Video imaging of walking myosin V by high-speed atomic force microscopy
Noriyuki Kodera,Daisuke Yamamoto,Ryoki Ishikawa,Toshio Ando, Nature, 2010

Super-resolution Microscopy collection

Nature methods highlights the recent developments in the super-resolution imaging field. This collection of articles from several leaders in the field highlights the diversity of super-resolution microscopy techniques being developed and the principles that allow them to overcome this long-standing limitation.

Click here to see the collection, which is also sponsored by Nikon.

Here are the articles in the collection:

1- Primer: fluorescence imaging under the diffraction limit. D. Evanko. Nat. Methods 6, 19–20 (2009)

2- Microscopy and its focal switch. S.W. Hell. Nat. Methods 6, 24–32 (2009)

3- Putting super-resolution fluorescence microscopy to work. J. Lippincott-Schwartz & S. Manley. Nat. Methods 6, 21– 23 (2009)

4- Subdiffraction resolution in continuous samples. R. Heintzmann & M.G.L. Gustafsson. Nat. Photonics 3, 362–364 (2009)

5- Single-molecule mountains yield nanoscale cell images. W.E. Moerner. Nat. Methods 3, 781–782 (2006)

6- Live-cell photoactivated localization microscopy of nanoscale adhesion dynamics. H. Shroff et al. Nat. Methods 5, 417– 423 (2008)

7- Spherical nanosized focal spot unravels the interior of cells. R. Schmidt et al. Nat. Methods 5, 539–544 (2008)

8- Whole-cell 3D STORM reveals interactions between cellular structures with nanometer-scale resolution. B. Huang et al. Nat. Methods 5, 1047–1052 (2008)

9- Super-resolution video microscopy of live cells by structured illumination. P. Kner et al. Nat. Methods 6, 339– 342 (2009)

Label-Free Nonlinear Microscopy reveals Zebrafish Cell Cycling

Together with more explorations of intrinsic nonlinear properties of the biological samples, the nonlinear microscopy has become an extensively used tool to demonstrate morphological visualization of biological structures.

A recent report in Science August(20) issue achieves 3 dimensional reconstruction of early Zebrafish Embryos. In this study, researchers designed a framework for imaging and reconstruction unstained whole zebrafish embryos for their 10 cell division cycles and also they reported the measurements along the cell lineage with micrometer spatial resolution and minute temporal accuracy.

Click here to read more about this report:
Cell Lineage Reconstruction of Early Zebrafish Embryos Using Label-Free Nonlinear Microscopy
Nicolas Olivier, Miguel A. Luengo-Oroz, Louise Duloquin, Emmanuel Faure, Thierry Savy, Israël Veilleux, Xavier Solinas, Delphine Débarre, Paul Bourgine, Andrés Santos, Nadine Peyriéras, and Emmanuel Beaurepaire (20 August 2010)
Science 329 (5994), 967.

Second harmonic generating (SGH) nanoprobes

A new type of nanoprobe is introduced for in vivo imaging, circumventing many of the limitations of classical fluorescence probes. These second harmonic generating (SGH) probes are nanocrystals that converts two photons into one photon of half of the wavelength under intense illumination. Unlike fluorescent probes, they don't photobleach or saturate with increasing illumination intensity.

The report onf SGH nanoprobes is reported in July issue of PNAS. Click here to read more..

Getting around the diffraction limit

Optical microscopy has been extensively used to observe biological processes, where counting and identifying of molecular structures are achieved for accurate measurements. To date, several promising technologies have been introduced to break the resolution limits of conventional microscopes (i.e diffraction limit ~200nm), including PALM,STORM and STED. These methods are called super-resolution techniques,where resolution is defined as the minimum distance or volume that can be measured between two identical particles in a given period of time. Since biological molecules are <5-10nm,getting molecular details requires imaging at this scale, which can be achieved by super-resolution methods. Another important method to break the diffraction limit is localization accuracy, where it's defined as the minimum distance or volume that one can locate a particle's position within a certain time period.Localization have paved the way to understand how some biological molecules move or change its position, including the motor protein analysis.

Simply, one should not confuse localization super-accuracy with super-resolution as aforementioned. Recently, Toprak et al. reviewed some of the methods that were used for both localization and super-resolution in fluorescence microscopy. Here is the article for further details:

Erdal Toprak, Comert Kural, Paul R. Selvin, "Super-accuracy and super-resolution getting around the diffraction limit," Methods in Enzymology 475:1-26 (2010).

Plasmonic Structured Illumination Microscopy

Another super resolution imaging method is reported in Nanoletters. Click here to read the paper.

We propose a super resolution imaging technique called plasmonic structured illumination microscopy (PSIM), which combines the structured illumination microscopy technique with the tunable surface plasmon interference. Because of the high-resolution enabled by using surface plasmon interference as an illumination source, PSIM possesses higher image resolving power compared with conventional structured illumination microscopy. To demonstrate the technique, we present two specific types of plasmonic structure designs for PSIM. The final images from the simulations show 3-fold and 4-fold resolution improvement compared with conventional epi-fluorescence microscopy.