A NEW METHOD FOR A NON-INVASIVE GLUCOSE- SENSING POLARIMETRY SYSTEM

Transcription

1 A NEW METHOD FOR A NON-INVASIVE GLUCOSE- SENSING POLARIMETRY SYSTEM Sunghoon Jang, New York Ciy College of Tehnology of CUNY; Hong Li, New York Ciy College of Tehnology of CUNY Absra Curren mehods of monioring blood gluose use invasive ehnologies suh as olleing blood samples. Developmen of an aurae non-invasive mehod will presen a grea advanage over urren mehods. Our researh group developed a non-invasive gluose-sensing polarimery sysem wihin physiologi gluose levels by applying advaned opo-eleronis ehnology. The auhors of his sudy demonsraed aurae resuls wih he sysem presened here. In a previous sudy, he auhors were suessful in deeing he opial roaion of in-vivo and ex-vivo gluose onenraions wihin he physiologi range of mg/dl due o a highly sensiive and sable losed-loop polarimery sysem. Alhough preliminary resuls from his sysem were suessfully demonsraed by he auhors in a previous sudy, he ompliaion of a losed-loop sysem reaes issues for fuure appliaions beause i will require more omponens and i is more diffiul o design and analyze he sysem. The auhors inrodue here a new, simplified open-loop non-invasive gluose-sensing polarimery sysem. Theories of he proposed mehod are inrodued and preliminary resuls are demonsraed. This sudy invesigaed he developmen of an open-loop opial gluose-sensing sysem ha used a simpler mehod o disinguish blood gluose levels wihin his physiologi range by using he aqueous humor of he eye. This is beause i has exremely fas response and reovery profiles wihou signifian delay, when ompared wih gluose onenraions in blood plasma. The resuls demonsrae ha no only is his noninvasive gluose-sensing deeor apable of monioring gluose auraely enough o saisfy medial-use rieria, bu is also apable of employing a more simplified mehod han exising onvenional losed-loop opial gluosesensing ehnologies. Inroduion Diabees mellius is a serious disease when he human body does no produe or properly use insulin. I has been one of he major healh problems in soiey. Ofen, diabees an lead o many serious medial problems inluding blindness, kidney disease, nerve disease, limb ampuaions, and ardiovasular disease (CVD). Aording o he Amerian Diabees Assoiaion, he esimaed os of diabeesrelaed healh are in he Unied Saes is approximaely $91.8 billion, annually, inluding $3. billion in dire medial oss [1]. The reen sudies [] of muli-ener Naional Insiue of Healh (NIH) [] indiaed ha he healh risks assoiaed wih diabees are signifianly redued when blood gluose levels are properly and frequenly onrolled [3]. I is learly indiaed ha i is pruden o measure blood gluose as ofen as five or six imes a day. Thus, i is very imporan ha proper monioring should be done by diabeis a home or a work [4] [5]. A presen, all exising mehods of home blood-gluose monioring require obaining a blood sample by priking a fingerip wih a needle. This mehod srongly disourages paiens ompliane, and has serious drawbaks beause of is assoiaed pain, inonveniene, and invasive naure [6]. A non-invasive mehod of monioring blood gluose would presen major advanages over urren mehods using invasive ehnologies. The auhors aemped o develop and demonsrae aurae resuls wih a non-invasive losed-loop opial-gluose sysem, wihin he physiologi gluose range of mg/dl. The proposed open-loop gluose-sensing opo-eleroni sysem used in his sudy also needed o be apable of monioring very low gluose levels wih he auray and preision ha would saisfy medial-use rieria; his mehod is also expeed o be fas and simple. The os of he proposed esing devie would be signifianly lower han for exising mehods beause only a monior wih an opial sensor would be required, and he high monhly expense of esing srips would be avoided. In addiion, paien aepane for his mehodology was expeed o be high, due o is non-invasive naure, and he fa ha i would be a simple and safe esing proedure. There has been an inreased demand for oninuous, noninvasive gluose-monioring ehniques [7], due o he inreasing number of people diagnosed wih diabees and he reogniion of he fa ha he long-erm ouome of hese paiens an be dramaially improved by a areful, frequen and aurae gluose-monioring mehod wih onrol. In a previous sudy [8] [9] [], he auhors reviewed several of he newes, minimally invasive and non-invasive gluosemonioring ehnologies under developmen or reenly inrodued. These inlude near infrared sperosopy (NIR) [10], mid infrared sperosopy (MIR) [11], radio wave impedane, opial roaion of polarized ligh [11], fluid exraion from he skin [1], and gluose-sensing ona lenses wih fluoresene deeion [11]. Alhough reen advanes in basi researh and linial appliaions in noninvasive opial gluose monioring are very enouraging for he fuure of his field, none of he aemps wih noninvasive opial gluose-sensing ehniques have resuled 36 INTERNATIONAL JOURNAL OF ENGINEERING RESEARCH & INNOVATION VOL., NO. 1, SPRING 010

2 hus far in he developmen of a sensor, whih allows monioring of gluose wih suffiien auray and preision [7], [3]. Therefore, i is neessary o develop a new ehnique o saisfy rieria suh as auray, low os, simpliiy in sampling and esing, porabiliy, and safey. Theory and Plan of Sudy The firs preision opial polarimeer using he Faraday effe was inrodued by Gilham [13], [14] in Rabinovih and Marh [15] inrodued he onep of using he aqueous humor gluose as a deeor of he blood gluose onenraion by measuring he polarizaion roaion. Subsequenly, Coe, Norhrop, and Fox [16], [17] developed a rue phase opial-gluose sensor o monior gluose onenraion. In 1997, Jang and Fox [18], [19] demonsraed ha a losed-loop polarimeer ould be realized wih a single Faraday roaor. In previous sudies [18], [19], he auhors inrodued new, simplified non-invasive gluose-sensing polarimery ehnology by inroduing heories and demonsraing preliminary resuls. Convenional opial gluose sensors [7], [11], [0], [1] are very ompliaed in sysemi design and performane beause hey adoped oudaed losed-loop sysems, whih are ineffiienly designed and implemened using addiional opial omponens and eleroni devies inluding a beam splier, phoo deeors, polarizers, Faraday modulaors, and lok-in amplifier wih addiional analyzing devies. In his sudy, he auhors aemped o invesigae and develop he open loop-opial gluosesensing sysem due o is simpliiy for ahieving higher auray and sabiliy, while ensuring sysem sensiiviy. The opial roaion due o he gluose ell will be proporional o he onenraion of he gluose and he pah lengh of he ell. The enire sysem sensiiviy an be onrolled by hanging he gain onsan of he lok-in amplifier. Figure 1 shows a basi open-loop polarimery sysem. The linearly polarized wave is emerging from he firs polarizer, where θ represens he axis of he firs polarizer. xˆ is he horizonal omponen of θ and ŷ is he verial omponen of θ. The linear polarizaion of he inerrogaing beam is modulaed by he opial hopper, whih replaed he Faraday modulaor used in previous researh, and is hen ransmied hrough a gluose ell, seond polarizer, phoo deeor, and lok-in amplifier, respeively. As illusraed in Figure 1, he linearly polarized wave emerging from he firs polarizer, an be represened as he following veor equaion, E = Esinθ xˆ + Eosθ yˆ (1) 1 The linear polarizaion of he inerrogaing beam is modulaed by he aion of he modulaing opial hopper suh ha φ = φ osω Then, equaion (1) beomes, E = Esin( θ + φ osω ) xˆ + Eos( θ + φ osω ) yˆ () When θ = 0 and φ is small, E Esin( φ osω )ˆ x + Eyˆ (3) Laser Figure 1. Blok diagram of an open-loop gluose polarimery sysem inluding gluose ell wih firs polarizer (P1) and seond polarizer (P) The x omponen of he eleri field an be expanded o yield, E Eφ osω (4) x The frequeny-doubling effe for rossed polarizers, where he axis of he seond polarizer is a a righ angle wih respe o he axis of firs polarizer, an be demonsraed by he following developmen, sine opial deeors are sensiive o he inensiy of ligh 1 I x = Ex Eφ osω = E φ os ω = E φ (1 + osω ) (5) The hange in linear polarizaion due o he opial roaion effe is E = E sin( + φ osω ) xˆ + E os( + φ osω ) yˆ (6) 3 I was found ha he deeed inensiy will be I x where: = E = E P1 x E 1 E E 3 ( φ E( + φ osω Opial Chopper E φ osω φ Gluose ell os ω + φ osω + ) 1 E φ ( 1+ osω ) + φ osω + φ + for small, φ φ = opial roaion due o he opial hopper = addiional opial roaion due o he gluose ell P E 4 Phoo Deeor (7) If a lok-in amplifier is onneed o he oupu of he A NEW METHOD FOR A NON-INVASIVE GLUCOSE-SENSING POLARIMETRY SYSTEM 37

3 phoo diode deeor wih a referene frequeny ω, is DC oupu is V = LE φ (8) V o L where L is he gain onsan of he lok-in amplifier and direly onains informaion abou he opial roaion due o he gluose moleule in he ell. From he above equaion, we an onlude ha he DC level of he lok-in amplifier in our open-loop opial-gluose sensing sysem will be dependen on he gain onsan of he lok-in amplifier, inensiy of he opial signal, and he opial roaions due o he opial hopper and he gluose medium. If we se all parameers as onsan, oher han he gluose medium, he sysem an dee he variane of DC levels due o opial roaion, whih is proporional o he onenraion of he gluose moleule in he medium. The heoreial response from he lok-in amplifier as a funion of he angle beween he wo polarizers is represened graphially in Figure. I was found ha his openloop polarimery sysem worked effiienly when lose o a 45 angle beween he wo polarizers. A key poin is ha he roaion hange, whih is indiaive of gluose onenraion, is now modulaed a he Faraday frequeny for oheren deeion. A V ou os θ 1 θ i θ 1 Figure. Graphial represenaion showing how he oupu from he lok-in amplifier depends on he angle (θ 1 ) beween he wo polarizers in Figure 1. Mehodology and Resuls θ The main omponens of he losed-loop opial gluose sensor using he opial roaion of he gluose moleule are illusraed in Figure 3. A HeNe laser (approximaely 1mW effeive oupu afer he firs polarizer, 633 nm), and a firs polarizer were used o provide linearly polarized ligh. The ligh was hen passed hrough a Faraday modulaor driven a abou 1. khz for he modulaion of he polarizaion veor and deeed by a phoo diode deeor afer onrolling is inensiy by a seond polarizer, whih is alled an analyzer. The lok-in amplifier provided an oupu signal, whih is a DC volage proporional o he ampliude of he 1. khz presen in he deeed signal from he phoo deeor and Region A: V due o ou DC opial roaion of gluose moleule (hange in DC offse). hen fed bak o he Faraday modulaor o lose he loop. This d oupu volage is fully moniored and reorded by an osillosope, and a single Faraday modulaor was used as a modulaor and ompensaor o provide modulaion and feedbak ompensaion ombined wihin he sysem. Therefore, he lok-in amplifier provided phase and frequenyloked deeion of he 1. khz omponen, whih iself was proporional o he ne roaion beween he wo polarizers posiioned a 45 o eah oher. The opial roaion due o he gluose ell, wih a pah lengh of one enimeer, is proporional o he onenraion of he gluose and he pah lengh of he ell. Thus, sensiiviy of he enire sysem an be onrolled by hanging he gain onsan of he lok-in amplifier. HeNe Laser P 1 Osillosope FM Gluose Cell P Audio Amp. Signal Generaor Eleronis HPF Lok-in Amp. Figure 3. Blok diagram of a designed and implemened losed-loop gluose-sensing polarimery sysem: P 1 and P are polarizers; FM is a Faraday Modulaor; he gluose ell onains various gluose soluions wihin he physiologi range; PD is he phoo diode deeor; HPF is he high-pass filer The losed-loop sysem was firs alibraed by measuring he DC oupu signal from he lok-in amplifier, while applying various modulaing frequenies in order o find he bes fi for he urren gluose-sensing sysem. The daa shown in Figure 4 (a) was obained from he DC oupu of he lok-in amplifier by hanging he angle of he seond polarizer. I was found ha he sysem sensiiviy was 37.01V/, whih means ha every 10 millidegree of roaion gives abou mv DC offse. Sine a praial gluose meer would need o dee a few millidegrees [] of roaion, his sysem had a signifian sensiiviy. Figure 4 (b) shows a alibraion run using he losed-loop sysem wih a gluose ell onaining dexrose-gluose in onenraions of 0, 100, 00, 300, and 500 mg/dl wihin he physiologi range. These daa ses were obained by using a single ell ha was refilled wih various gluose onenraions a eah measuremen. The averaged se of daa from Figure 4 (b) was ploed afer aking 10 measuremens for eah onenraion o minimize errors due o he one-enimeer lengh of he gluose ell. The linear regression shown in Figure 4 (b) yielded [gluose], whih indiaes ha for every 18.5 millidegree/(100 mg/dl), he dexrose-gluose moleule onribues abou 0. millidegree of opial roaion o he sysem. PD 38 INTERNATIONAL JOURNAL OF ENGINEERING RESEARCH & INNOVATION VOL., NO. 1, SPRING 010

4 The auhors suessfully demonsraed aurae resuls wih he previously-designed non-invasive losed-loop polarimery gluose-sensing sysem wihin physiologi gluose levels. This sudy also aemped o invesigae and develop an opial gluose-sensing sysem, in order o ahieve higher auray and ensure sensiiviy wih a simpler mehod using he open-loop gluose-sensing polarimery sysem shown in Figure 5 by applying advaned opoeleronis ehnology. Figure 4-a. Plo of he DC oupu from he lok-in amplifier (LIA) as a funion of he seond polarizer roaion in he losed-loop opial-gluose sysem illusraed in Figure 3 Figure 4-b. Plo of he waveforms inludes DC oupu from he lok-in amplifier (LIA) agains gluose onenraion in he losed-loop gluose sensor HeNe Laser P 1 CH Gluose Cell P Chopper Driver PD Lok-in Amp. (LIA) The daa shown in Figures 6-a o 6-i were obained from he DC oupu of he lok-in amplifier wih he angular orienaion of he seond polarizer. Various gains were also applied in order o alibrae sysem sensiiviy and sabiliy. Then, he sysem sensiiviy was measured by monioring he DC oupu of he lok-in amplifier using a fi of he daa as shown in Figure 6-j. I was found ha he sysem sensiiviy was 6.44 V/, whih means ha every 10 millidegree of roaion gives abou 64.4 mv DC offse oupu. This sensiiviy would be enough o dee a few millidegrees of roaion for a gluose moleule. Alhough he sysem sensiiviy was lower han he previously developed losed-loop gluose-sensing polarimery sysem, he auhors are onfiden and opimisi abou his new open-loop sysem beause he sysem sensiiviy an be improved by a faor of 10 wihou enounering major problems. From previous experiene, he opial roaion of he gluose moleule was observed wihin he physiologi range a he sysem sensiiviy, mv DC offse for every 10 millidegree analyzing he polarizer roaion. Due o he fa ha an absoluely dark room was no available for esing his sysem, here were erain levels of inerfering opial noise involved in he urren sudy. To improve sysem sensiiviy and sabiliy, fuure measuremens will be made in an absolue dark room. Osillosope Figure 6-a Figure 5. Blok diagram and aual sysem of a designed and implemened open-loop polarimery gluose sensor: CH is an opial signal hopper The general onfiguraion of he sysem presened in Figure 7 is similar o he previous seup; however, he auhors added an ex-vivo goa eye or an arifiial eye o he sysem in order o dee peneraing ligh hrough he anerior hamber of he eye filled wih aqueous humor. Also, he measured V DC oupu depends on he gluose onenraion, A NEW METHOD FOR A NON-INVASIVE GLUCOSE-SENSING POLARIMETRY SYSTEM 39

5 Figure 6-b Figure 6-f Figure 6- Figure 6-g Figure 6-d Figure 6-h Figure 6-e whih an be deeed by he lok-in amplifier. The sysem analysis wih an ex-vivo goa eye or arifiial eye will be ompleed in a fuure sudy. In his presen sudy, he auhors have presened a simplified, non-invasive gluosesensing polarimery sysem by presening heories and Figure 6-i demonsraing preliminary resuls. In a follow-up sudy, he auhors hope o ahieve he inrinsi opial roaory effe using onvenional opial roaion in he presene of ex vivo living issue or an arifiial eye. 40 INTERNATIONAL JOURNAL OF ENGINEERING RESEARCH & INNOVATION VOL., NO. 1, SPRING 010

6 Referenes Figure 6-j Figure 6. Demonsraed alibraions of he open-loop gluosesensing polarimery sysem. (a) o (h) are plos of V DC oupu from he lok-in amplifier as a funion of he seond polarizer roaion in he open-loop sysem illusraed in Figure 5 a various lok-in amplifier sensiiviies. (i) is a omposie plo of all sensiiviies in he lok-in amplifier. (j) is a plo of he V DC oupu from he lok-in amplifier in he linear regression range a he sensiiviy 5 1 mv HeNe Laser P 1 CH Figure 7. Shemai blok diagram of he open-loop gluosesensing polarimery sysem inluding an arifiial eye Conlusion Osillosope Arifiial Eye Chopper Driver Gluose Cell Opial gluose-sensing ehniques using he opial roaory effe of gluose have many advanages over exising invasive and noninvasive mehods, sine he mehod is based on shining a brief pulse of ligh ino he fron of he eye. The auhors previously showed ha i is possible o isolae he lens/aqueous refleion and dee polarizaional hanges. However, measuremens in he presene of a living eye will presen many hallenges beause he issues are more variable han nonliving opial omponens due o he naure of orneal birefringene. Furher work will opimize his sysem in order o ahieve he desired sensiiviy, sabiliy and auray. One hese hurdles are overome, he opial gluose-sensing mehod sudied and developed in his sudy an be miniaurized using urren inegraed opis, eleronis, and advaned miro-fabriaion ehnologies. This ehnique also has grea poenial for providing an inexpensive, fas, reliable, aurae, and ompa non-invasive gluose sensor for diabei paiens in he near fuure. P PD Lok-in Amp. (LIA) [1] Amerian Diabees Assoiaion, Eonomi Coss of Diabees in he U.S. in 00, Diabees Care, Volume 6, number 3, Pages , Marh 003. [] Naional Insiue of Healh (NIH), Naional Diabees Saisis 007 hp://diabees.niddk.nih.gov/dm/pubs/saisis/ [3] Gavin J.R., The Imporane of Monioring Blood Gluose, Touh Briefings, US Endorine Disease 007 Issue, Pages 1-3. [4] Coser S.; Gulliford M.C.; Seed P.T.; Powrie J.K.; Swaminahan R., Monioring Blood Gluose Conrol in Diabees Mellius: A Sysemai Review, Healh Tehnology Assessmen, 000, vol. 4, no. 1. Pages: i-iv, [5] Driskill W.T., Diabees Coninues o he Naion s Fourh Leading Cause of Deah, Healh Eduaor, 1, Marh 3, [6] Garg S.; Zisser H.; Shwarz s.; e al, Improvemen in Glyemi Exursions wih a Transuaneous, Real- Time Coninuous Gluose Sensor, Diabees Care, Volume 9, no. 1, Pages 44-50, January 006. [7] Coe G.; Le R.; Pishko M., "Emerging Biomedial Sensing Tehnologies and Their Appliaions," IEEE Sensors Journal, Vol. 3, No. 3, Pages , June 003. [8] Jang S.; Ciszkowska M.; Russo R.; Li H, A New Approah o Gluose Monioring Using a Non- Invasive Oular Amperomeri Elero-Chemial Gluose Sensor for he Diabeis, he ASEE Mid- Alani Seion Spring 006 Conferene, Brooklyn, NY, April 8-9, 006. [9] Jang S.; Russo R.; Li H., Modifying he Exising Non-invasive Opial Gluose Sensing Devie and Demonsraing he Opial Roaory Effe of Gluose in he Presene of Gluose Medium, he ASEE Mid-Alani Seion Spring 007 Conferene a NJIT, Newark, NJ, April 13-14, 007. [10] Maruo K.; Tsurugi M.; Tamura M.; Ozaki Y., In Vivo Noninvasive Measuremen of Blood Gluose by Near-Infrared Diffuse-Refleane Sperosopy, Applied Sperosopy, vol. 57, no. 10, Pages (9), Oober 003. [11] MNihols R.; Coe J., Opial gluose sensing in biologial fluids: an overview, Journal of Biomedial Opis, vol. 5(1), Pages 5-16, 000. [1] Klonoff D., Non-Invasive Blood Gluose Monioring, Diabees Care, vol. 0, no. 3, Pages , Marh [13] Gilham E.J., "A High-preision Phooeleri Polarimeer," Journal of Sienifi Insrumens, Vol. 34, Pages , November [14] Gilham E.J., "New Design of Speropolarimeer," Journal of Sienifi Insrumens, vol. 38, Pages 1- A NEW METHOD FOR A NON-INVASIVE GLUCOSE-SENSING POLARIMETRY SYSTEM 41

7 5, January [15] Rabinovih B.; Marh W.F.; Adams R.L., "Noninvasive Gluose Monioring of he Aqueous Humor of he eye," Diabees Care, vol. 5, no. 3, Pages 54-58, May 198. [16] Coe' G. L.; Fox M.D.; Norhrop R.B., "Gluose Sensor Developmen Using an Opis Approah," Proeedings of he 16h Annual Norheas Bioengineering Conferene, IEEE EMBS, Penn Sae Universiy, Universiy Park, Pennsylvania, Marh 6-7, [17] Coe' G.L.; Fox M.D.; Norhrop R.B., "Laser Polarimery for Gluose Monioring," Proeedings of he 1h Annual IEEE EMBS Conferene, Philadelphia, Pennsylvania, November 1-4, [18] Fox M.D.; Censor D.; Jang S.; Welh L., Muliple wavelengh non-invasive oular polarimery for gluose measuremen for managing of diabees, SBIR Program Final Repor [19] Jang, S.; Fox M.D., "Opial Gluose Sensor Using a Single Faraday Roaor," Proeedings of he 3rd Annual Norheas Bioengineering Conferene, IEEE EMBS, Durham, New Hampshire Marh 3-4, [0] Baba J.S.; Cameron B.D.; Coe G.L., Effe of Temperaure, ph, Corneal Birefringene on Polarimeri Gluose Monioring in he Eye, Journal of Biomedial Opis, 7(3), Pages 31-38, July 00. [1] Baba J.S.; Cameron B.D.; Coe G.L., Opial Roaion and Linear and Cirular Depolarizaion Raes in Diffusively Saered Ligh from Chiral, Raemi, and Ahiral Turbid Media, Journal of Biomedial Opis, 7(3), Pages 91-99, July 00. [] Jang S.; Fox M.D. Opial Sensor Using he Magnei Opial Roaory Effe of Gluose, IEEE- LEOS, vol. 1, Pages 8-30, April [3] Koshinsky T.; Heinemann L., Sensors for gluose monioring: ehnial and linial aspes, Diabees/meabolism researh and reviews, vol.17, issue, Pages , Marh 001. HONG LI is urrenly an Assoiae Professor in Deparmen of Compuer Sysems Tehnology a New York Ciy College of Tehnology of CUNY. She reeived her M.S. degree in Mahemais from P. R. China and Ph.D. degree in Mahemais from The Universiy of Oklahoma. Her researh has been foused on sysem modeling and parameer esimaion in variey fields of appliaions. She has published a number of papers wih group of researhers in he fields of ivil engineering and biomedial engineering. Professor Li also has years of experiene of sofware developmen in indusries before she joined CUNY as fauly member. Professor Li may be reahed a hli@iyeh.uny.edu. Biographies SUNGHOON JANG is urrenly an Assisan Professor in Elerial and Teleommuniaions Engineering Tehnology a New York Ciy College of Tehnology of CUNY. He reeived he B.S. degree in Elerial Engineering from he Kyung-nam Universiy, Korea, and his M.S.E.E degree in Elerial and Compuer Engineering from New Jersey Insiue of Tehnology, and his Ph.D. degree in Biomedial Engineering from Universiy of Conneiu. Dr. Jang is a member of IEEE and BME. His ehnial areas inlude digial signal proessing, opo-eleronis, and onrol sysems in Biomedial Engineering. He has published a number of papers in hese areas. Dr. Jang eahes in Elerial and Teleommuniaions Engineering Tehnology. Professor Jang may be reahed a sjang@iyeh.uny.edu. 4 INTERNATIONAL JOURNAL OF ENGINEERING RESEARCH & INNOVATION VOL., NO. 1, SPRING 010