Technology

New Peer Review References.

Poster ASMS 09: Electric Field Enhanced MALDI Sample Prep & 100% nL Liquid DART Sample lntroduction BOTH via IBF. ESI too? Sauter's ASMS 2009 Poster.

JASMS Paper 6/09: "Measuring Charge for the Real Time Induction Based Fluidic MALDI Dispense Event Verification and Nanoliter Volume Determination."

Polymer Paper 5/09: "Electric Field Enhanced Crystallization for synthetic polymer MALDI-TOF Mass Spectroscopy via Induction Based Fluidics.

 Click above for videos. Download other older articles, posters at bottom of this page. Please forward the video "millisecond nanoliters."

"sample preparation contributes more to assay variability than instrument variability." Nature Biotechnology Vol. 27 No. 7, pg 639, July 2009.

Is the dried droplet "method"  science? The literature is replete with examples where nLs enhanced MALDI sensitivity (Sze, Woods, Callahan, Bogan, Tu, Gross, Harmon et al and NIH below.)

"Methods to concentrate sample spots on targets improve detection."
MDS's Sciex's Tom Covey et al, JASMS, 2006, 17,1129-1141.

"Reducing noise is an important challenge to gain a better analysis of MW of entire protein."
G. Bolbach, et al., JASMS, 2007, 18, 1880-1890.

"Use nanoliters & IBF because quantitative MS & qualitative MS are simply different parts of the same equation."
A.D. Sauter, J.J. Downs, et al,“Analytical Chemistry. 1986, 58, 1665.

Induction Based Fluidics (IBF)

IBF is a simple way to move (or move and treat) liquids. In IBF, one imparts a charge to liquids so they can be energized such that they will be launched or projected to targets of diverse types using simple devices; such as, syringes or alternatively in more complicated embodiments.

In IBF, liquids are charged and that action allows for the performance of many simple, useful tasks including flying nanoliter and microliter quantities of liquids, non-touch to targets of all types; such as, humans; plants; animals; microscope slides; multiple-well plates; scientific instruments and other devices. Through the presentation of the physics of IBF, it has been shown that unlike piezoelectric, sound, or any other technologies that are applied to transport liquids at low volumes that IBF technology can 1) kinetically project drops to targets of all types, 2) dynamically direct the liquids in flight to targets (a required, trait for small volumes of liquids) and details depending 3) count them on arrival. This simple technology has been called “elegant” by the director of R&D of a major mass spectrometry firm.

The nanoliter regime offers a number of obvious benefits over larger volume regimes in the lab and elsewhere. These include significant savings in expensive reagents, major reduction in human exposure to toxic chemicals, allergens, agents, viruses, etc. The nanoliter regime also reduces waste disposal costs. Because IBF has a massive dynamic range (µL to fL), it has a substantial application space. It is a useful laboratory tool that has broad applications elsewhere. For example, IBF can be used for simple sample dilution; the analysis of proteins, peptides and synthetic polymers by MALDI; other sample preparation in chemical analysis; drug delivery; drug discovery; radiochemistry; homeland security/defense applications; forensics; the sampling of or drug delivery to human beings; in medical diagnostics; and in the manufacture of unique chemical and other entities, e.g., polymers and electrets. Finally, IBF also allows non-touch dispensing in the microliter regime as well for more classical assays, and it also has interesting consumer applications, e.g., gluing.

To understand IBF, consider the physics of a flowing laminar system. (IBF does not need flowing or hybrid systems as the flow can be purely electrokinetic, but that is beyond the scope of this description.) The liquid volume passing through a tube is given by the Hagen-Poiselle equation. The volume of fluid (V) that flows down a small diameter capillary tube per unit of time (t), is proportional to the fourth power of the radius of the tube (r), the pressure pushing the fluid down the tube (P), the length of the tube (L), and the viscosity of the fluid (μ). Note, V is linear in t.

V = ((π r⁴ P)/ 8Lμ) t

Now, if we grow a drop on a capillary under these conditions, (or if we make a drop with our syringe or in some other manner), we can then charge (q) the drop using an electric field E . Upon charging, the liquid will experience the electric force (qE) imparted by induction, similar to the manner in which gas phase ions experience the qE force in mass spectrometers. Since electric fields can be generated inexpensively and they can be rapidly toggled on and off with high accuracy and precision, the electrical force acting on liquid drops can be changed rapidly and accurately as well and very economically.

F = qE

Now, because F is a vector, one can also direct the drop to a target. For a charged drop with charge q0, which depends liquid specifics and system specifics, the value q is realized when the once “on” field is turned off.

q = q₀ e^{(–t / λ)}

That is, the system relaxes exponentially where λ = (ε₀ ε_r / κ), and  ε₀ is the dielectric constant of free space, ε_r is the relative permittivity, κ is the solution conductivity and t is time. Of course, while the field is on, the drop remains charged and it can be manipulated by varying E to vary F elec. and hence, drop position.

Now, a charged liquid drop in an electric field not only can experience the qE force, but it experiences other, different forces as well in the atmosphere in x, y, and z space, depending on the specifics of the system. Using standard, well-known physics, Newton’s 2nd law, we can equate the forces (electric, drag, buoyancy, gravity, and coulombic) acting on a drop to those acting in the direction, x, as:

Fx = m (ax) = m (dvx/dt) = F_elec + F_drag + F_buoy + F_grav + F_coul

Force equations can also be written for the y and z coordinates; therefore, with accurate model equations for Fy and Fz, we can actually calculate the trajectories of the drops (distances of travel, d over some time, t) knowing that Vx = dx/dt, Vy = dy/dt, Vz = dx/dt, the initial position of the drop, and that V² = Vx² + Vy² + Vz² . That discussion; however, is beyond the scope of this description.

So by using induction to apply electric charge to drops, one can launch and direct liquids to targets in a non dispersive manner with excellent accuracy and precision. With additional measurement tools, one can even quantitate the liquid volume dispensed. Furthermore, in various related arrangements liquids can be treated, i.e., filtered, purified, chromatographed, etc., as well, in a highly parallel manner. Because one does not have to connect each channel (in IBF the field does the “connection” through the process of induction), the cost of highly parallel dispensing device does not have to scale or increase with the number of channels. So, IBF has excellent liquid dispensing and liquid treatment attributes and low per channel costs, as well.

Why IBF Improves MALDI.

There are a number of reasons that IBF can improve MALDI. Firstly, we can accurate dispense and locate the liquid using an electric field and our nanoLiter Cool Wave dispenser, unlike those using the dried droplet "method" which we assert is not science. Also it doesn't spray everywhere. Then because the nanoliter drops are spatially concentrated compared to uL drops, one gets more bang for your photon buck, i.e., more S and less N per laser shot. Next, and this has just been published in Polymer, the electric field can anneal the sample helping to improve the morphology and perhaps the mixing as compared to the coffee rings that other deposition techniques make. It is also thought, but not proven, that less noise is created in the plume with nL depositions as compared to uL depositions reducing plume reactions (neutraliztions and collisions) that destroy the analytical ion of interest. 

Why IBF Can Improve DART, DESI, ICP/MS, ESI, etc.

Get the picture ?

Fx = m (ax) = m (dvx/dt) = F_elec + F_drag + F_buoy + F_grav + F_coul 

F_coul  inhibits the spatial concentration of analyte on a surface or for that matter in the transfer of analyte into a MS! !!!!!

In IBF, only two coulombic terms defocus the drops due to the drop before and the other drop after any single drop. A spray has many defocusing terms which means less can get where you want it or into the ion source, as reported at ASMS 2009. (This is also why nano-ESI is more sensitive than normal flow ESI.) IBF affords other unique possibilities because we shoot drops in a straight line. Note: in another brand new application, we've been informed that another major government group as demonstrated that nL SIMS of a viscous iquid, improves SIMS results. Uniquely, IBF can handle viscous liquids too ! So IBF is simple, and unique. Also, in it's first application at NIH, IBF was shown to increase the sensitivity of tubilins by ca. 100X, whereby a PTM of a brain cancer sample was found in it's first application! More work is ongoing at NIH this summer.

Even better at Pittcon 2009, we shot 10, 20, 50 and 100 nLs of an aqueous solution directly into a DART. 100 % of it getting spectra in our first attempt. Imagine how you could improve your sensitivity with our Cool Wave devices in front of your DART or next to your DESI where we could provide tight spots to standardize your system. This is the same technology that has dramatically increased the sensitivity of MALDI by facrtors of 5, 10 and 100 for peptides, proteins and synthetic polymers.

Our tech is protected by a power deep, IP fence which we are interested in sharing and licensing.