Analytical Currents: Monitoring live-cell secretion

come these limitations, Gary Hieftje and colleagues at Indiana University, ... the cells was also limited because fresh nutrients weren't con- tinuous...
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ANALYTICAL CURRENTS

Monitoring live-cell secretion Robert Kennedy and colleagues at the University of Michigan have designed a microfluidic device that can quantitatively monitor secretions from live cells over time. The device could be useful for studying the secretory processes of live cells, and it could have applications in drug development.

Labeled insulin

Waste

Antibody

Kennedy and colleagues previously developed a microfluidic device that could detect insulin release by single islets of Langer-

Gate

Islet

hans (Anal. Chem. 2003, 75, 4711–4717). However, the device

Perfusion inlet

lacked a way to continuously flow solutions through the sample chamber. This limitation imposed restrictions on monitoring secretions over time and observing behavioral changes of the islet cells in response to drugs and other chemicals. The viability of

A microfluidic device that is 2.5  7.5 cm in size has been developed to monitor the secretion of insulin over time. (Adapted with permission. Copyright 2004 Royal Society of Chemistry.)

the cells was also limited because fresh nutrients weren’t consecretion over time in response to the glucose concentration.

tinuously supplied. The device has now been modified so that the islet cells in the

The investigators also monitored the behavior of the islet cells

sample chamber can be provided with fresh media and solutions

with different types of buffers, showing that the immunoassay for

through an inlet perfusion channel, into which fluid is pumped by

detecting insulin in the device is compatible with more than one

gas-driven pressure. The investigators determined that the de-

type of solution. However, precipitation of salts from certain types

tection of insulin is unperturbed by the perfusion of solutions and

of buffers can block the microchannels. Kennedy and colleagues showed that their device can be

that the cells are not damaged by fluid flow. Kennedy and colleagues next demonstrated that insulin se-

cleaned and re-used. And although the investigators use their

cretions from individual islets can be monitored as the glucose

device to monitor insulin secretion by islet cells, they point out

concentration is altered between 3 and 11 nM. The device’s de-

that with minor changes, it is amenable for studies of other cell

tection limits are sensitive enough to track oscillations in insulin

types. (Lab on Chip 2004, doi 10.1039/B404974H)

Array detector for LA-ICPMS The use of laser ablation (LA) as a sample-introduction method for inductively coupled plasma MS (ICPMS) allows for the direct analysis of a wide range of solid samples. However, shot-to-shot variations in the laser power and interactions between the laser and the sample can cause erratic responses, which make quantification difficult. To overcome these limitations, Gary Hieftje and colleagues at Indiana University, the University of Arizona, and the Pacific Northwest National Laboratory 302 A

have developed a new array detector for LA-ICPMS that detects multiple elements simultaneously. Simultaneous detection is used to eliminate the noise that is characteristic of the ablation process. Variations in the laser can be corrected for by normalizing the signal for each m/z value to the total ion signal. As a result, analyses can be performed with single laser pulses. This benefit leads to improved depth resolution, less sample consumption, and better precision.

A N A LY T I C A L C H E M I S T R Y / S E P T E M B E R 1 , 2 0 0 4

Using the new detector combined with a LA sample-introduction system, an ICP ionization source, and a Mattauch–Herzog mass spectrograph, the researchers achieved detection limits in the tens to hundreds of femtograms range and an isotope-ratio precision better than 0.02% RSD, with an integration period of 1 h. The instrument also performed depth-profile analysis with a depth resolution of 5 nm per ablation event. ( J. Am. Soc. Mass Spectrom. 2004, 15, 769–776)