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Ions, molecules, and bio-markers measurements using BioMEMS

Presentation By Danut Dragoi, LPBI

Small or large molecules and ions are traditionally determined in specific clinical labs facilities utilizing complex instrumentation and standard operation procedures. Same analytical clinical results can be obtained today from specialized miniaturized bioMEMS. The miniaturized instrumentation and procedures use less sample and highly sophisticated algorithms for data processing, usually intended without sample preparation or lengthy time analysis. These features reduce the costs associated with the lab work, provide rapid results to the patient and doctors. In this presentation, the talk is focused on  ions, molecules, and bio-markers measurements using BioMEMS as shown in the first slide.

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An overview of the presentation includes the items shown below.

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Slide #3 shows a palm size DNA and RNA sequencer, see link in here, that I assume astronaut Scot Kelly recently used in outer space, International Space Station,  to monitor his DNA and RNA changes as an effect of low gravitation and cosmic radiation, during his close to one year work in outer space. The tiny new device shown in the picture below called the MinION™, is developed by Oxford Nanopore Technologies, promises to help scientists sequence DNA in space. NASA’s Biomolecule Sequencer investigation is a technology demonstration of the device.

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The physical principle of the DNA sequencer is based on the perturbation of the electric current that flows trough the nanopore plate when one strand of DNA macromolecule, with nucleotides attached, goes through a small pore of 5 nm diameter. In this way, by recording the electrical signals, the genetic code is revealed, see link in here.

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The picture in slide #5 taken from here, shows how the physical principle explained before is applied.

 

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The one-strip bio-sensor structure, common for glucose concentration measurements shows three layers of electrodes, see link in here, that provide an electrical signal proportional to the amount of glucose in a tiny amount of blood.

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This slide explains the principle and the chemical reaction at the electrodes for a common glucosometer, see link in here.

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The principle of glucosometer can be applied to other molecules, such as bio-markers that represent large molecules associated with an antigen tumor in human plasma, see link in here.  Photo image below is for a portable strip reader.

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Slide #9

The chemical reactions specific to a glucose meter, shown bellow, are taken from here.

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Slide #10

The schematic below shows how one strip biosensor for bio-markers works, see link in here. The complexity of a bio-marker molecule requires conditional measurements for accuracy and reproducible results.

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Slide #11

The schematic below is a continuation of slide #10 in which standard bio-markers are introduced in order to have a comparison between a test line and a control line besides additional antigens, gold antigen conjugate, and antibodies.Details of how all these markers interact on the strip biosensor, see link in here.

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In this slide, which is a continuation of slides #10 and slide #11, the goat anti-mouse IgG is introduced as a control sample in the control line.

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In many situations, one strip amperometric (electrical current) is not enough to perform the measurements, as in salt daily intake determination, see link in here.The analyte in this case is determined from the analysis of an image taken from the strips, see link in here.

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The technique described in here, has two strips for measurements. In this way the ions in human body fluids, like Na+ can be successfully determined utilizing BioMEMS such as that described in here, and here.

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NB-Inspired from Na+ ions determination, a possibility of similar measurements exists for K+ ions.

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Slide #17 introduces the long range surface plasmon polariton (LRSPP) technique , which is similar to surface enhanced Raman scattering (SERS) technique. When the sample is functionalized with G protein than the interaction between components is reflected in the optical cavity power measurements, which is exploited on determining the ratio of light kappa and lambda polymeric chains.

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The slide shows an optical plasmonic biosensor for leukemia detection, see link in here.

 

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The schematic on slide #19 shows how specificity of protein G, human IgG kappa and lambda, goat anti-human IgG kappa and lambda as pure standards work on optical plasmonic method.

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The output optical power of the LRSPP device versus time of introducing the analyte and the standards shows specific signal shifts for anti-human lambda IgG on HKS (high kappa serum) and anti-human kappa IgG on HKS.  If the ratio of the two signal is outside of a small given range, see link in here, than the measurements indicate the presence of  the cancer cells.

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This slide shows the description of chemiluminescence method applied on a chip, see link in here, that become more popular with the development of measurements on micro-fluids using sensitive photo detectors arrays.

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The schematic below, taken from here, shows three sections of the chip, in which tiny capillaries lines take the sample without micro-pumping using the capillary effect, separates the light molecules from the heavy, and bring them in an area where chemiluminiscent effect takes place, emitted photons detected by an array of sensitive detectors and their signal electronically processed.

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This slide highlights the detection process that takes place towards the end of the capillary, see link in here.

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This slide illustrates a sample of signals adapted from a photo-detector array, see link in here.

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In conclusion, heavy analytes of bio samples can be determined with BioMEMS based chemiluminescence effect, many analyte solutions can get through a relative long capillary path using BioMEMS that are prone to miniaturization. The method of detecting photons from analyte interaction with a bioenzime-substrate with mono and multi-strips trend to be the generalization of actual R & D miniaturized devices. The new analytical micro-devices based on sensitive photo-detectors array reduces the actual costs of clinical analyzes and increases the speed of analytical process.

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Source

http://www.saltcounts.com/

https://www.nanoporetech.com/community/start-using-minion

http://www.nasa.gov/centers/ames/research/technology-onepagers/nanopores_gene_sequencing.html

Click to access amperometric-test-strips-for-point-of-care-biosensors-an-overview.pdf

Click to access AJBMS_2009_1_07.pdf

http://spie.org/newsroom/technical-articles/6268-optical-plasmonic-biosensor-for-leukemia-detection?ArticleID=x116720

https://sites.google.com/site/inescmn/home/research/mems-and-lab-on-chip-devices/lab-on-chip-devices

 

 

 

 

 

 

 

 

 

 

 

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BioMEMS based Optical Sensors

Author of Presentation: Danut Dragoi, PhD

Optical sensors are so well developed that many applications can benefit from them. Important applications in medical field that utilizes embedded optical sensors are using the BioMEMS. In this presentation we focus on BioMEMS based optical sensors in ophthalmology, eyes artificial retina, LASIK, micro endoscope, plasmonic devices with single molecules detection utilizing SERS-Surface Enhance Raman Scattering in which photon interaction (scattering) with bio-cells is a major effect of the detection. It will be shown how cancer detection works (utilizing kapa/lambda ratio).

The presentation will focus also on eye vision correction, vision for the blind, and virtual reality for entertainment.

Slide 4 shows the results of the interaction of photons with living cells. Examples are given to illustrate the physical effects of the interaction. The abbreviations used in the text are: abs for absorption, H for Hydrogen, e for electron, m* for excited mass of the living cell, ElemPart for elementary particles.

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Photon as an elementary particle, can be found in lasers, the best source of artificial light today. As we can remark on Slide 5 , the intensity of the lasers of very high power in peta watts range, one peta watts is 10 raised to the power of 15 watts, is expected to play a major role in the future of medicine.

 

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Slide 6 shows the world’s most powerful laser fired at Japanese Lab of Osaka University.

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On Slide 6 the laser beam is so intense, 2PW, so that the scattering from the air molecules can be seen on very large distances.

Slide 7 shows schematically our natural sensor, the eye, that works on visualizing objects like a tree exposed to natural light of Sun, in which light reflects / scatters in all directions, the lens of the eye focuses some rays on retina that give a signal to the brain through the optical nerve.

 

 

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Slide 8 gives the location of visual spectrum in the general electromagnetic spectrum, in which color green is in the middle of visible spectrum. The nature selected the maximum of sensitivity of our eyes to be green color that coincides with the color of chlorophyll, the green pigment, present in all green plants.

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Slide 9 shows the branch of eye care called Ophthalmology, in which correction of vision is done utilizing eye glasses or LASIK, an eye special surgery on cornea of the eye.

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Slide 10 shows three options of eye correction of vision, normal vision gasses, contact lenses, and LASIK..Slide10

 

Slide 11 explains LASIK procedure, which is laser assisted in situ keratomileusis. In the three picture is shown the process of precise cut of the top of cornea, tissue removal using an eximer laser, whose wavelength is so short that does not penetrate the ocular lens, and the last step of flipping back the cut from cornea in the first stage. In many countries milions of people opted for this procedure.

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Slide 12 is an attempt to explain the etymology of keratomileusis in the word LASIK.Slide12

 

Slide 13 suggests what beyond LASIK procedure, in which the concept for blindness is given as a solution utilizing implantable photo-detector arrays.

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Slide 14 compares natural optical sensors with artificial optical sensor based on Si microelectronic technology.

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Slide 15 shows a bio-optical sensor made by Anitoa, a company in Palo Alto CA. What is special about this photo-detector is its high sensitivity pushed toward one photon detection.

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Slide 16 shows an endoscope with one fiber optic and two electrical lines, which is recognized as an Optical Coherent Topography device.

Slide16The optical fiber guides a laser beam towards the end of the fiber where a GRIN lens, which is a gradient index lens, focuses the beam on a mirror that rock around an axis in order to scan the beam on the object, then the reflected beam goes back on mirror through the GRIN lens and the fiber again where an image is produced.

 

Slide 17 shows a MEMS endoscope made by  Santec, where we recognise all elements described in previous slide.

 

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Slide 18 compares sensors sensitive to visible spectrum made in nature, fruit flies eye, and those sensors made in the lab utilizing the model of fly eye. Because the resolution of the recreated eye fly is poor we expect that technology to not be used. The actual Si microelectronics is much better in producing high performance photo detectors.

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Slide 19 shows a ‘smart’ contact lens to monitors the pressure inside the eye that can produce glaucoma and possibly lose the sight.

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Slide 21 shows schematically  a prosthetic retina for people who have the photoreceptors retina destroyed, either by disease or by an accidental  exposure to a laser beam.

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Slide 22 shows an implantable BioMEMS subretinal Alpha IMS for blind people.

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Slide 23 shows the number of pixels in natural vision for different types of eyes, starting with low pixels for insect and ending with very high pixels for predatory birds. The horizontal axis describes the number of images . The red lines represent the memory storage of pixels for different vision systems.

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Slide 24 shows the implantable retina micro-array from Sandia National Lab.

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Slide 25 an artificial retina from Lawrence Livermore Lab.

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Slide 26 describe other advanced optical devices based on SERS (Surface Enhanced Raman Scattering) for single molecule detection such as cancer cells, toxic molecules, poison molecule and other.

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Slide 27 gives the definition of plasmon and Raman spectroscopy which is s the measurement of the wavelength and intensity of in-elastically scattered light from molecules. The Raman scattered light occurs at wavelengths that are shifted from the incident light by the energies of molecular vibrations.

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Slide 28 is for how SERS works.

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Slide 29 explains  the principle of SERS for detection of single molecules.

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Slide 30 shows the principle of SERS enhancement of the spectrum  using Ag nano particles.

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Slide 31 examples of molecules detected by SERS,

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Slide 32 shows a mini-device plasmonic biosensor for leukemia detection.

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Slide 33 shows how the optical plasmonic device is tuned to detect cancer cells by measuring IgG-kappa and IgG-lambda ratio.

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Slide 34 shows how the ratio IgG-kappa and IgG-lambda is determined in clinical diagnostic utilizing SERS wave guides.

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Slide 35 shows a MEMS device as a mini-spectrometers in visible range of the electromagnetic spectrum.

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Slide 36 shows how the mini-spectrometers works.

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Slide 37 shows  a mini-spectrometer at work utilizing a laptop, an absorption cuvette and optical fibers for input into spectrometer and electrical connections between a laptop and spectrometer.

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Slide 38 shows a mini MEMS USB spectrometer based WiFi.

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Slide 39 shows MEMS USB spectrometer connected to an iPhone.

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Slide 40 shows an integrated color sensors for blood glucose meters.

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Slide 41 shows an optical device for measuring Oxygen saturation of blood.

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Slide 42 shows how the oxymeter works.

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Slide 43 shows the glaucoma can destroy the optical nerve producing total blindness.

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Slide 44 gives the definition of glaucoma.

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Slide 45 shows the micro-systemic approach for glaucoma.

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Slide 46 shows bio MEMS coil for glaucoma. The graph on the slide show a calibration curve, resonant frequency of the coil versus pressure in a water testing device, where the pressure of water is well known and the frequency measured precisely with a pressure instrument.

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Slide 48 shows the definition of cataract which is a leading eye problem for the older.

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Slide 49 shows a BioMEMS artificial lens.

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Slide 49 shows how artificial lens is working.

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Slide 51 shows a sub-retinal BioMEMS principle of working.

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Slide 52 shows a higher complex BioMEMS artificial retina system.

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Slide 53 shows a BioMEMS artificial retina system by Professor Wilfried Mokwa of RWTH Aachen University.

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Slide 54 shows  a BioMEMS and epiretinal stimulation from Retina Implant AG.

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Slide 55 shows a Bionic Microchip at the back of the eye with 1500 pixels.

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Slide 56 shows a bionic microchip installed on the back of the eye.Slide56

Slide 57 shows a schematic of retinal bionic implant, 3×3 mm with a light processing cells, which is the latest generation of a light sensitive chip.

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Slide 58 shows  a contact lens for Virtual Reality applications. Notice in this application the eye is healthy and normal functioning.

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Slide 59 shows a description of  contact lenses for Virtual Reality applications.

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Slide 60 and 61 show the conclusions.

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This is the end of the presentation. Thank you!

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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