Method for molecule detection utilizing digital micromirror technology

Biologic molecules and pathogens in a sample substance are detected by utilizing the multiplicity of mirrors in a digital micromirror device as test sites to which molecular probes are attached and to which the sample substance is applied. A molecule or pathogen bonded on the surface of a micromirror activated with an appropriate molecular probe can be detected by optical projection or software interrogation of the array of micromirrors.

FIELD OF THE INVENTION 
This invention relates to a method of detecting and screening organic 
molecules and biologic pathogens by employing molecular probe activated 
digital micromirror technology. 
BACKGROUND OF THE INVENTION 
A first field of science relevant to the invention is the detection and 
identification of biologic molecules and pathogens. 
As taught, for example, in U.S. Pat. No. 5,653,939, issued Aug. 5, 1997 to 
Hollis et al, a multiplicity of detection sites are formed on a suitable 
substrate and a sample substance containing molecular structures sought to 
be detected and identified is applied over the sites. Each test site 
contains probes designed to bond with a predetermined target molecular 
structure. The probes in each site differ in a predetermined known manner 
from the probes in the other sites so that different target molecules in 
the sample may bond with different probes. A signal is applied to the test 
sites and certain electrical, mechanical and/or optical properties of the 
sites are detected to determine which probes have bonded to an associated 
target molecular structure. The bonded molecules may then be removed from 
the respective sites and subjected to testing and analysis. 
Numerous techniques have been employed for the detection and identification 
of DNA, RNA, and other biologic molecules and pathogens. These techniques 
include autoradiography, fluorescent microscopy, charge coupled devices, 
electronic and optical hybridization, electromagnetic devices, dynamic 
random access memory devices, mechanical resonators, and the like. Each 
technique has its advantages and disadvantages. 
A second field of technology relevant to the invention is that relating to 
digital light processing display technology based on a 
microelectromechanical systems device known as the digital micromirror 
device. 
A digital micromirror device is comprised of thousands, even hundreds of 
thousands, of individual mirrors, each usually sixteen microns square, and 
each fabricated on hinges on top of a static random access memory (SRAM). 
Each mirror is capable of receiving its own unique instructions and can 
receive a new instruction every 1/1000th of a second. 
Each micromirror is a light switch that can reflect light in one of two 
directions depending upon the state of the underlying memory cell. With 
the memory cell in the (1) state, the respective mirror rotates to a 
+10.degree.. With the memory cell in the (0) state, the respective mirror 
rotates to a -10.degree.. Each mirror is capable of oscillating between 
these positions at rates of 1,000 cycles per second to produce pulses or 
bursts of reflected light. 
The digital light processing system is utilized in television and similar 
technologies to convert digital video signals into a visible digital 
display by transmitting to the human eye rapid digital light pulses that 
the eye interprets as a color analog image. The digital micromirror 
device, which is available from Texas Instruments Incorporated, Dallas, 
Tex., is a high speed reflective digital light switch which when combined 
with image processing, memory, light source and optics forms a digital 
system capable of projecting large high contrast color images with 
excellent fidelity and consistency. 
The technology of digital light processing has not been related to the 
science of detecting and identifying biological molecules and pathogens. 
SUMMARY OF THE INVENTION 
The object of the present invention is to unite the scientific technologies 
above described; specifically, to utilize the digital micromirror 
technology of Texas Instruments for the detection and identification of 
biologic molecules and pathogens. 
It is not the intent of the invention to belabor any of the molecule 
detection techniques previously employed, but instead to bring a novel and 
unique approach to the art of molecule detection and identification. 
The objects and advantages of the invention will become apparent from the 
following detailed description.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
The following is a detailed description of certain embodiments of the 
invention presently deemed by the inventor to be the best mode of carrying 
out his invention. 
In accordance with the present invention, an array of 
microelectromechanical micromirrors is employed to detect, either by 
optical projection or through software interrogation, the presence of a 
molecule or biologic pathogen bonded on the surface of a micromirror that 
has been activated with an appropriate molecular probe. The multiplicity 
of mirrors in the array serve as test sites in a manner similar to the 
practice of the art as above described. Such use of an array of 
micromirrors as test sites provides a straight forward method to screen 
large numbers of target molecules or pathogens quickly and efficiently for 
bioactivity, identification, and subsequent testing. 
Molecular probes can be attached to the digital mirror surfaces by physical 
or chemical mechanisms. A physical method comprises adsorption or 
absorption of the probes onto the surfaces. A chemical method comprises 
bonding the probes onto the mirror surfaces by either ionic or covalent 
bonding. By employing one or more of these methods, a wide variety of 
molecular probes can be attached to the mirror surfaces. 
To identify new drug candidates by optical projection using this invention, 
a practitioner would attach different bioluminescent or chemiluminescent 
probes to different mirror surfaces of the array, expose the array to a 
sample substance containing target molecules of interest, direct an 
appropriate light source onto the array, and project the resulting image 
on a screen or other surface. Locations where target molecules react with 
a probe will fluoresce in the projected image and the individual test 
sites (micromirrors) can be addressed with software to identify the 
precise location and the precise probe at that location for the molecule 
of interest. 
A software interrogation method for identifying target molecules utilizes 
the surface mass change on micromirrors oscillating at 1,000 cycles per 
second to detect the presence of molecular reactions at specific 
locations. For example, molecular probes can be attached to the 
micromirrors, the array of mirrors can then be oscillated and exposed to a 
sample substance containing target molecules of interest, and if there is 
a chemical reaction at one or more probes, the mass of the respective 
mirrors will change and that will cause the rate of oscillation to change, 
i.e., slow down. The software will detect and identify the mirror or 
mirrors with slower oscillation and, knowing what probe was at that 
location, a target candidate can be identified. 
Once target molecules are located, the identified mirror location can be 
covered with a photomask to protect the target molecule while the rest of 
the mirror array is washed with an appropriate solvent. The mask can then 
be removed by standard photolithography techniques, the target molecule 
washed off the mirror, identified and tested appropriately. 
The invention lends itself to high volume, fast, lost cost screening and 
identification of biologically active molecules and pathogens. 
The objects and advantages of the invention have thus been shown to be 
attained in a convenient, practical, facile and economical manner. 
While preferred embodiments of the invention have been herein described, it 
is to be appreciated that various changes, rearrangements and 
modifications may be made therein without departing from the scope of the 
invention as defined by the appended claims.