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Berkeley Researcher Develops Device That Interfaces Lab-on-Chip Tech With Mass Spec


Daojing Wang
Principal investigator
Lawrence Berkeley National Laboratory
Name: Daojing Wang
Position: Principal investigator, proteomics research group, life sciences division, Lawrence Berkeley National Laboratory
Background: PhD, chemistry and biophysics, Princeton University; postdoc in chemistry at the University of California, Berkeley

Daojing Wang led a team of scientists who developed a device they say enables large-scale integration of mass spectrometry and lab-on-chip analysis in proteomics research.
Specifically, the technology, a monolithically integrated silicon/silica microfluidic channel with a multinozzle nanoelectrospray emitter, may help improve the detection of low-abundance proteins.
The device is described on the American Chemical Society’s website.
ProteoMonitor spoke with Wang last week about his work. Below is an edited version of the conversation.
Can you describe your device?
Basically we tried to develop a new interface between microfluidics [and] mass spectrometers. This mass spectrometer was just … a conventional … nanoelectrospray mass spectrometer [that we interfaced] with a silicate-based microfluidic device.
We developed a novel yet very straightforward way of microfabricating this kind of device, and we introduced a new concept: a so-called multinozzle [nanoelectrospray emitter array]. Most conventional electrospray tips are just one nozzle, so we introduced this new concept, a multinozzle emitter, meaning you have one channel but [at] the end you have a multinozzle, just like a shower head.
Based on the capillary type of emitter, you have one capillary, but at the end it’s very sharp. You reduce the inner diameter that way. But if you go to a much smaller diameter, it easily gets clogged. The back pressure is much higher, so our idea was that if you want to have this much smaller [inner diameter], it’s better to use multiple smaller [inner diameters] simultaneously, so that for each individual [inner diameter] back pressure may be high, but overall, it releases the pressure, just like a shower head.
And this cannot be done with a capillary, obviously. A capillary has only one inlet [and] one outlet. So we used a microfabricated technique to design and fabricate the multinozzle emitter.
So those are the two new things: one is a multinozzle concept, the other thing is, I believe, for the first time a silicate-based interface between microfluidics and a conventional mass spectrometer. People have done polymer-based [interfaces] … but they have limitations. Polymer always has limitations in terms of adsorption, the background, and organic solvent compatibility.
Basically, if you run a protein through [a polymer-based microfluidic], the protein will be adsorbed onto the polymer itself. So that’s why silicate-based is, I believe the direction, to go in order to integrate a microfluidic system with an electrospray mass spectrometer.
Adsorption doesn’t happen with a silicate-based microfluidic?
I think it’s much smaller and there are so many surface derivatization techniques out there, we always coat the surface to reduce the adsorption. Most capillaries are silicate capillaries in electrospray experiments.
Has no one tried to use the silicate interface before?
They have tried, but it’s very hard to fabricate. We kind of introduced a novel but straightforward way of fabricating silicate channels. We started with silicon, just a conventional silicon chip, then we fabricated a channel, then we coated the silicon with a silicate layer. Then we sacrificed the silicon inside to fabricate a silicate channel. Eventually we had a silicate microfluidic channel on a silicon chip. Also the emitter is made of silicate.
What has been the issue with lab-on-chip technology in relation to mass spectrometry?
I think the biggest problem for lab-on-chip is integration: How do you integrate multiple functionality on a chip and connect this device with the outside world?
So this interface we designed basically can solve one of these challenges. You have a chip, you do all the separation, everything on the chip. But eventually, you need some sort of detection. Previously, most of the work focused on chip detection using either electrochemical detection or fluorescence detection.
But this way, once we have a good interface, you [can] use more than one technique, such as mass spectrometry, to get molecular information of your analytes.
For fluorescence detection, you need prior knowledge of your proteins or some kind of marker. Then you can use fluorescent dye or a GOP protein to enable the system. But for mass spectrometry you can do de novo detection. You don’t need prior knowledge of the molecules.
Is your device producible on a mass scale?
You can design a chip, you can fabricate a silicate, or silicon device, so … it has the potential to [be made on a mass production scale]. But right now we are in the research and development stage, so if it’s in an industrial environment, I think it can be done.
Is there a specific type of mass spectrometer your device works particularly well with?
No, this device is not dependent on the [type] of mass spectrometer. Any electrospray mass spectrometer can be used as the back-end detector.
So anything from the basic ion-trap to the Fourier transform mass spectrometer?
Yeah, basically anything that works with electrospray will work, because we provide just the interface. The back-end detection does not affect this interface.
What does this device mean to proteomics researchers?
It means in the long run, we can fabricate fully integrated microchips that can do a lot of things. I think it will change microfluidics in terms of how we design a microfluidic system. If we use microfluidics, then we need [fewer] samples. It will [also] require less sample consumption [and] it can be made disposable so [there’s less] contamination between samples. It also gives you higher throughput.
Will this allow them to identify or characterize more proteins?
Well, that depends on the sensitivity of the mass spec. There are a lot of applications; obviously I can’t state them all, but I think the significance of our work is to provide this new concept, multinozzle. If you have multinozzle, it may improve the sensitivity of the detection. This will improve your detection for low-abundance proteins.
What are you working on now?
Basically, we’re going to incorporate this into a larger microfluidic system, so integration is the word. We’re working on further optimizing this design, and integrating this emitter.

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