Lab on a Chip Blog

Today, calling is not the only function of the cell-phone, but in some cases just a nice side function. A new function developed by Aydogan Ozcan and co-workers is the ability to perform a rapid blood analysis using your cell phone.

In a previous article the group at University of California, Los Angeles, USA, showed that a cell-phone with some add-on components can be used to test for the presence of peanuts in cookies¹. In this new article, a module is demonstrated which can be used to measure characteristics of blood. Three variables which can be tested with their system are the haemoglobin content and white and red blood cell concentrations.

After connecting a base attachment to the cell phone (in this case an Android phone), three different add-on components can then be attached. Each component consists of a lens, light source and chamber for the sample. For the white blood cell count, the cells are first fluorescently labelled and placed in a chamber with known volume. Subsequently the sample is excited and the fluorescence is measured in the perpendicular direction. In case of the red blood cell count, unlabelled cells in a specific volume are optically detected using bright field illumination. For the last application, the measurement of the haemoglobin content, the absorbance of the lysed blood sample is determined, which is directly related to the concentration of haemoglobin. The user-friendly phone app allows you to choose one of the three analyses and input parameters, such as the sample dilution factor. It subsequently processes the captured images to generate the test results, which can be uploaded to a database or sent on to clinicians

Although some sample pre-processing is necessary, the blood analysis will take about 10 seconds for each image taken. The results of the cell phone module are in good agreement with a standard test, thereby making it applicable for blood analysis at point of care.

References

1. Ahmet F. Coskun, Justin Wong, Delaram Khodadadi et al. A personalized food allergen testing platform on a cellphone. Lab Chip, 2013, 13, 636–640

Cost-effective and rapid blood analysis on a cell-phone
Hongying Zhu, Ikbal Sencan, Justin Wong, Stoyan Dimitrov, Derek Tseng, Keita Nagashima and Aydogan Ozcan  
DOI: 10.1039/C3LC41408F

Loes Segerink is a Post-Doctoral researcher in the BIOS Lab on a Chip group, University of Twente, The Netherlands

A new method for the direct, bottom-up growth of a SERS substrate within a microfluidic channel, developed at the University of Connecticut, will enable the inexpensive fabrication of SERS-integrated devices.

Surface enhanced Raman scattering (SERS) spectroscopy is a powerful method for analyte detection and identification.  SERS relies on the electric field enhancement provided by nanostructured metal surfaces to amplify the Raman scattering “fingerprint” of adsorbed molecules, enabling specific detection down to the single molecule level¹.  Previously, SERS integration into practical devices has been limited, partly due to the cost and difficultly of fabricating SERS substrates and microfluidic channels separately, then aligning and bonding them together.  In this HOT article, researchers at the University of Connecticut led by Prof. Yu Lei have devised a method to fabricate a novel nanostructured SERS substrate directly within existing microfluidic channels, greatly simplifying the construction of such devices². 

Previous SERS-integrated microfluidic devices have utilized silver plates fabricated via laser writing³ and silver nanoparticles created using physical vapor deposition⁴ as SERS substrates. These devices provide high detection sensitivity, but are costly to produce due to the top-down fabrication methods used.  The advantage of the new method by Parisi et al. is the ability to synthesize a SERS substrate bottom-up and in situ, reducing the complexity and cost of device fabrication.  SERS experiments can then be carried out immediately.

In situ electrodeposition and galvanic displacement are used to fabricate a nanostructured SERS substrate (right) within a microfluidic device (left)

In the new technique, copper nanowalls coated with carbon are synthesized inside a microfluidic channel via electrodeposition.  This is accomplished by applying a voltage across part of the channel while copper acetate flows through.  Next, silver nitrate flows through the channel, and a galvanic replacement reaction results in silver nanoparticles coating the nanowalls.  Then, an analyte solution flows through the channel and adsorbs onto the substrate, allowing the user to measure SERS.  The authors used crystal violet as an example analyte to demonstrate the sensitive in-channel detection capability, measuring the SERS of analyte concentrations down to 50 pM.

The researchers hope that their fabrication technique will ultimately allow SERS to be integrated into various microfluidics-based biological and chemical sensing platforms, increasing the power and flexibility of these devices. 

References

1. J. Kneipp et al., Chem. Soc. Rev., 37, 1052–1060, 2008. 
2. J. Parisi et al., Lab on a Chip, 13, 1501–1508, 2013.
3. B.-B. Xu et al., Lab on a Chip, 11, 3347–3351, 2011.
4. Z. Geng et al., Sensors and Actuators A, 169 (1), 37–42, 2011.

Read this HOT article in Lab on a Chip today:

In situ synthesis of silver nanoparticle decorated vertical nanowalls in a microfluidic device for ultrasensitive in-channel SERS sensing
Joseph Parisi, Liang Su and Yu Lei
DOI: 10.1039/C3LC41249K

 This article is featured in the web collection Lab on a Chip Top 10%

Katie Mayer is a post-doctoral researcher in the Walt Laboratory at Tufts University, USA

Researchers at York University in Toronto have developed an integrated microfluidic device to facilitate analysis of modified protein structures after biochemical reactions.  

The platform guides a protein right through from a controlled reaction, functional labeling, and fragmentation zones to a coupled mass spectrometer for determination of the protein’s secondary structure. Using this device, the group conducts the first dynamic structural analysis of the β-lactamase enzyme TEM-1 to identify key regions of the enzyme that affect catalytic activity.  TEM-1 is the enzyme that provides bacterial resistance to β-lactam antibiotics.

Protein binding events crucial to protein function can change protein shape directly at the binding site or through another site (an allosteric mechanism). One example of allostery is when the binding of oxygen to one heme site in hemoglobin increases oxygen affinity at other heme sites due to structural changes. For hemoglobin, functional labeling during binding events and mass spectrometry (MS) protein structure analysis was used to find the 3 sets of residues responsible for the allosteric mechanism at each heme site.¹ The integrated microfluidic platform described here by Derek J. Wilson’s group enables similar experiments with faster sample transfer to electrospray ionization for MS analysis.

This integrated microfluidic platform first incubates the protein of interest with a reactant for a controlled time. Then, the amide protons of the backbone are functionally labeled with deuterium and the labeled protein is digested in a pepsin-functionalized region. Finally, the fragments are ionized and transferred into a time-of-flight mass spectrometer (Q-TOF MS). Labeled peptides are quickly delivered to the spectrometer resulting in high retention of the proton label.

Evaluating TEM-1 after incubation with its inhibitor clavulanate, Wilson’s group notes that regions of the protein which undergo slow changes in deuterium uptake correspond to allosteric transitions and occur on the protein periphery. Rapid changes occur to reposition specific residues, “loosening” some structures and “locking up” others near the active site.

These measurements are the first to analyze TEM-1 inhibition dynamics and demonstrate the great utility of this microfluidic platform to facilitate exploration of allosteric mechanisms and other dynamic structural changes affecting protein function.

1. I. A. Kaltashov and S. J. Eyles, in Mass Spectrometry on the Frontiers of Molecular Biophysics and Structural Biology: Perspectives and Challenges, Wiley Online Library, 2012, pp.186-208.

An electrospray MS-coupled microfluidic device for sub-second hydrogen/deuterium exchange pulse-labelling reveals allosteric effects in enzyme inhibition
Tamanna Rob, Preet Kamal Gill, Dasantila Golemi-Kotra, and Derek J. Wilson
DOI: 10.1039/C3LC00007A

Sasha is a PhD student at Stanford University working with Professor Beth Pruitt’s Microsystems Lab. Her research interests focus on designing microscale devices for studying cell mechanobiology and the biophysical underpinnings of cell-cell and cell-substrate interactions.