Cellphone-based Diagnostic Technologies

In many third world and developing countries, the distance between people in need of health care and the facilities capable of providing it constitutes a major obstacle to improving health. One solution involves creating medical diagnostic applications small enough to fit into objects already in common use, such as cell phones — in effect, bringing the hospital to the patient. Here we list some of the emerging cell-phone based diagnostics technologies:

  1) Cell-phone lensfree microscope: UCLA researchers have advanced a novel lens-free, high-throughput imaging technique for potential use in such medical diagnostics, which promise to improve global disease monitoring, especially in resource-limited settings such as in Africa.
 Ref: http://pubs.rsc.org/en/content/articlelanding/2010/lc/c003477k

  2) Cell-phone imaging with microchip ELISA: Ovarian cancer is asymptomatic in the early stages and most patients present with advanced levels of disease. The lack of cost-effective methods that can achieve frequent, simple and non-invasive testing hinders early detection and causes high mortality in ovarian cancer patients. Here, we report a simple and inexpensive microchip ELISA-based detection module that employs a portable detection system, i.e., a cell phone/charge-coupled device (CCD) to quantify an ovarian cancer biomarker, HE4, in urine. Integration of a mobile application with a cell phone enabled immediate processing of microchip ELISA results, which eliminated the need for a bulky, expensive spectrophotometer.
 Ref: http://pubs.rsc.org/en/content/articlelanding/2011/lc/c1lc20479c

3) Mobile phone based clinical microscopy: Light microscopy provides a simple, cost-effective, and vital method for the diagnosis and screening of hematologic and infectious diseases. In many regions of the world, however, the required equipment is either unavailable or insufficiently portable, and operators may not possess adequate training to make full use of the images obtained. Counterintuitively, these same regions are often well served by mobile phone networks, suggesting the possibility of leveraging portable, camera-enabled mobile phones for diagnostic imaging and telemedicine. Toward this end 1we have built a mobile phone-mounted light microscope and demonstrated its potential for clinical use by imaging P. falciparum-infected and sickle red blood cells in brightfield and M. tuberculosis-infected sputum samples in fluorescence with LED excitation.
 Ref: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006320

 4) Cell-phone based platform as a biomedical device: In this paper we report the development of two attachments to a commercial cell phone that transform the phone's integrated lens and image sensor into a 350× microscope and visible-light spectrometer. The microscope is capable of transmission and polarized microscopy modes and is shown to have 1.5 micron resolution and a usable field-of-view of 150×150 with no image processing, and approximately 350×350 when post-processing is applied. The spectrometer has a 300 nm bandwidth with a limiting spectral resolution of close to 5 nm. We show applications of the devices to medically relevant problems.
 Ref: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017150

5) Telemedicine tools with cell-phone cameras and paper microfluidics: This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field.
 Ref: http://pubs.acs.org/doi/abs/10.1021/ac800112r

 And also other technologies are coming up soon by various researchers...

Bleaching/blinking assisted localization microscopy

Superresolution imaging techniques based on the precise localization of single molecules, such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), achieve high resolution by fitting images of single fluorescent molecules with a theoretical Gaussian to localize them with a precision on the order of tens of nanometers. PALM/STORM rely on photoactivated proteins or photoswitching dyes, respectively, which makes them technically challenging. We present a simple and practical way of producing point localization-based superresolution images that does not require photoactivatable or photoswitching probes. Called bleaching/blinking assisted localization microscopy (BaLM), the technique relies on the intrinsic bleaching and blinking behaviors characteristic of all commonly used fluorescent probes. To detect single fluorophores, we simply acquire a stream of fluorescence images. Fluorophore bleach or blink-off events are detected by subtracting from each image of the series the subsequent image. Similarly, blink-on events are detected by subtracting from each frame the previous one. After image subtractions, fluorescence emission signals from single fluorophores are identified and the localizations are determined by fitting the fluorescence intensity distribution with a theoretical Gaussian. We also show that BaLM works with a spectrum of fluorescent molecules in the same sample. Thus, BaLM extends single molecule-based superresolution localization to samples labeled with multiple conventional fluorescent probes. For more: Biological Sciences - Cell Biology: Dylan T. Burnette, Prabuddha Sengupta, Yuhai Dai, Jennifer Lippincott-Schwartz, and Bechara Kachar Bleaching/blinking assisted localization microscopy for superresolution imaging using standard fluorescent molecules PNAS 2011 108 (52) 21081-21086; published ahead of print December 13, 2011, doi:10.1073/pnas.1117430109

Optogenetics: controlling cell function with light

Nature method's method of the year 2010 has been announced on an emerging method that is called Optogenetics. The combination of genetic and optical methods enabled scientists to explore biological processes with high temporal and cell-specific resolution. Not only neuroscience but also other cell/tissue related fields have now started to utilize optogenetics to open new landscapes for the study of biology.
Here is the video explaining the method of optogenetics:


Here you can reach to the news, articles and reviews on this promising method: MOY 2010, Nature Method

You may want to also visit the Stanford optogenetics resources

Finally, here are the recent articles on optogenetics:

(1) Global and local fMRI signals driven by neurons defined optogenetically by type and wiring, Nature 2010

(2) Optogenetics: Controlling the Brain with Light , Scientific American 2010

(3)Decoding the Brain with Light, Technology Review, 2009

(4)Optogenetics 3.0, Cell 2010

(5)Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures, Nature Protocols 2010

Protein localization using electron and fluorescence nanoscopy

Molecular topography of a cell can be successfully monitored by combining powerful imaging techniques such as electron microscopy and fluorescence nanoscopy ( STED or PALM). Recently, Prof. Erik M Jorgensen and his colleagues described a correlative fluorescence electron microscopy technique to localize protein on specific organelles. Here organelles first are revealed by electron microscopy and proteins are monitored by fluorescence imaging. As a result of image correlation between these two imaging modalities, proteins can be localized with nanometer accuracy. The paper also demonstrates localization of histone proteins on mitochondria.

Here is the paper that was published in Nature Methods: "Protein localization in electron micrographs using fluorescence nanoscopy"

X-ray microscopy resolves three-dimensional cellular ultrastructures

Partially coherent object illumination allowed researchers to reconstruct the three-dimensional ultrastructures of cells such as the double nuclear membrane, nuclear pores, nuclear membrane channels, mitochondrial cristae and lysosomal inclusions. These results demonstrated visualization of structures at ~36-nm (Rayleigh) and ~70-nm (Fourier ring correlation) resolution.

Here is the paper that was reported in Nature Methods Journal: "Three-dimensional cellular ultrastructure resolved by X-ray microscopy"

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