Page 203 - An Introduction to Microelectromechanical Systems Engineering

182 MEMS Applications in Life Sciences

typically 25 nucleotides long. Finally, all probes are deprotected, the substrates are
diced, and they are packaged in plastic flow-cell cartridges for use.
25
15
With 25 nucleotides in a sequence, there are 4 (equal to 10 ) different combi-
nations that can be made with this process. However, with a final chip size of 1.28
cm , there is only enough space for about 320,000 squares with different sequences.
2
Thus Affymetrix produces chips with only preselected sequences, targeting specific
applications (e.g., detecting strains of E. coli or hereditary neurological disorders in
humans). If different sequences or longer lengths are desired, custom arrays can be
made either with a new mask set or with a special maskless project system, such as
one based on Texas Instruments’ DLP (see Chapter 5), available from BioAutoma-
tion of Plano, Texas [21].
Another microarray market leader is Agilent Technologies. One product, the
Human 1A Oligo Microarray, has over 18,000 probes per 1- by 3-in glass slide with
lengths of 60 nucleotides [23]. Agilent uses inkjet technology (see Chapter 4) to
write the probes, base by base, with processing similar to that for the Affymetrix
probes. Picoliter volumes of nucleotide “ink” write round spots approximately 130
µm across. In addition to standard products, custom arrays can be produced with a
shorter turnaround time than with the masking production method. Agilent also
manufactures the Microarray Scanner for reading the arrays and producing com-
puter output. The large quantity of data produced by DNA analyses has spawned a
new field of study termed bioinformatics, which seeks to develop algorithms to han-
dle large genetic databases.

Microelectrode Arrays

Electrodes are extremely useful in the sensing of biological and electrochemical
potentials. In medicine, electrodes are commonly used to measure bioelectric signals
generated by muscle or nerve cells. In electrochemistry, electric current from one or
many electrodes can significantly alter the properties of a chemical reaction. It is
natural that miniaturization of electrodes is sought in these fields, especially for
applications where size is important or arrays of electrodes can enable new scientific
knowledge. Academic research on microelectrodes abounds. The reader will find a
comprehensive review of microelectrodes and their properties in a book chapter by
Kovacs [24].
In simple terms, the metal microelectrode is merely an intermediate element
that facilitates the transfer of electrons between an electrical circuit and an ionic
solution. Two competing chemical processes, oxidation and reduction, determine
the equilibrium conditions at the interface between the metal and the ionic solution.
Under oxidation, the electrode loses electrons to the solution; reduction is the exact
opposite process. In steady state, an equilibrium between these two reactions gives
rise to an interfacial space charge region—an area depleted of any mobile charges
(electrons or ions)—separating a surface sheet of electrons in the metal electrode
from a layer of positive ions in the solution. This is similar to the depletion layer at
the junction of a semiconductor p-n diode. The interfacial space charge region is
extremely thin, on the order of 0.5 nm, resulting in a large capacitance on the order
2
of 10 F per cm of electrode area. Incidentally, this is precisely the principle of
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