A paper on

CANCER DETECTION USING SMART PHONES

By G.Thanusha

CONTENTS Topic
1.Introduction 2.TOOLS USED IN SMART PHONES TO DETECT CANCERS 2.1Preparation of target DNA 2.2For the detection of cancer using Micro-NMR

page number
3 6 6 11

3.CONCLUSION

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4.REFERENCES

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1.Introduction:
Smart phones may have provided millions of people with hours of mindless entertainment, but their real value may lie in the hands of clinicians at the patients bedside. Accurate diagnosis and staging of tumours through analysis of core biopsies is essential for ensuring that patients receive rapid treatment with the most appropriate cancer drugs. However, current techniques for analyzing tumour biopsies such as immunohistochemistry and flow cytometry are costly and time-consuming and require more tissue than biopsies often contain, necessitating that patients be subjected to repeat biopsies. When we are feeling under the weather a visit to the doctors' surgery or hospital is a necessary evil to find out what is wrong with us. But, if a team of scientists have their way, we may soon be able to get a diagnosis for our illnesses simply by using a mobile phone from the comfort of the armchair. Backed by government funding, South Korean scientists have developed new mobilephone technology designed to diagnose disease. Incredibly, this could result in instant diagnosis' for illnesses from just a droplet of blood or saliva on a Smartphone's touchscreen. And those behind the revolutionary technology say the recognition rate is almost 100 per cent accurate and as effective as conventional medical equipment. The technology was developed on the basis of the touchscreen's capacity to detect the minute electrical signals generated by a fingertip's touch. That ability is called 'capacitive sensitivity'. A team at the Korea Advanced Institute of Science and Technology said when its technology is commercialised, it will revolutionise diagnostic medicine around the world.

Professor Park Hyun-Gyu says his team's research will enable mobile phones to diagnose a range of diseases from cancer to diabetes. He said biomolecules, like those produced by diseases, transmit similar signals that a touchscreen can recognise. Mr Hyun-Gyu said: 'If you have a certain type of DNA or proteins, the touchscreen would react in the same way as a finger's electrical signal is detected.'

A team of scientists at Korea Advanced Institute of Science of Technology (KAIST) said in a paper published in Angewandte Chemie, a German science journal, that touch screen technology can be used to detect biomolecular matter, much as is done in medical test. "It began from the idea that touch screens work by recognizing the electronic signs from the touch of the finger, and so the presence of specific proteins and DNA should be recognizable as well". The touch screens on smartphones, PDAs or other electronic devices work by sensing the electronic charges from the user's body on the screen. Biochemicals such as proteins and DNA molecules also carry specific electronic charges. According to KAIST, the team's experiments showed that touch screens can recognize the existence and the concentration of DNA molecules placed on them, a first step toward one day being able to use the screens to carry out medical tests. "We have confirmed that (touch screens) are able to recognize DNA molecules with nearly 100 percent accuracy just as large, conventional medical equipment can and we believe equal results are possible for proteins," Park told Reuters TV."There are proteins known in the medical world like the ones used to diagnose liver cancer, and we would be able to see the liver condition of the patient. "The research team added that it is currently developing a type of film with reactive materials that can identify specific biochemicals, hoping this will allow the touch screens to also recognize different biomolecular materials. But confirming that the touch screen can recognize the biomolecular materials, though key, is only the first step. Since nobody would put blood or urine on a touch screen, the sample would be placed on a strip, which would then be fed into the phone or a module attached to the phone through what Park called an "entrance point." "The location and concentration of the sample would be recognized the same way the touch of the finger is recognized".

Researchers in the US have developed a device that works with a smartphone to diagnose a suspicious lump in a patient and determine within an hour if it is benign or cancerous. The current procedure for diagnosis of suspicious lumps is to use a needle to extract a sample from the lump and then to send the cells to a pathology laboratory for examination. The sample is stained to look for tell-tale proteins and the cell shape is examined. The results are obtained within a few days, but are occasionally inconclusive. Dr Ralph Weissleder of the Massachusetts General Hospital in Boston and colleagues have developed a miniaturized nuclear magnetic resonance (NMR) scanner that identifies molecules by the way their nuclei are affected by magnetic fields. It also attaches magnetic nanoparticles to proteins to allow specific proteins, such as those found in tumor cells, to be identified. The gadget was tested on suspicious cells collected by fine needle aspiration from 50 patients. Because the samples needed are so small, cells could be taken from several areas of the suspected tumor. The samples were labeled with magnetic nanoparticles and then injected into the micro-NMR machine. The results can be read by connecting the device to a smartphone loaded with a specially-programmed application. The samples tested revealed nine protein markers for cancer cells. When the results for four of these proteins were combined they allowed the team to produce a diagnosis. The tests and analyses took an average of less than one hour for each patient and resulted in accurate diagnosis in 48 of the 50 patients. Another test produced 100% accuracy in 20 patients. Standard pathology tests on similar biopsies produce an accurate diagnosis in 74 to 84 percent of cases. Dr Weissleder said being able to sample the suspected tumor at several sites made the test more accurate. He said having the results available within the hour is a great advantage because it would reduce patient stress as people hate the days of waiting for standard pathology results to arrive, not knowing whether or not they have cancer. The greater accuracy of the micro-NMR would also cut the number of repeat biopsies needed.

In their paper, the micro-NMR machine could be used to test cancer patients to determine if they are responding to drugs by analyzing for specific proteins in blood samples.

2.TOOLS USED IN SMART PHONES TO DETECT CANCERS:

For the detection of bio molecular senses:
2.1Preparation of target DNA Amplification of a specific site of Chlamydia trachomatis gene encoding virulence protein was performed on a PCT-0200 (Bio-rad, Hercules, CA) thermo cycler in a 50 L solution containing 1 L of template, 0.25 M of each primer (forward: 5TTAATGGAAAAGTTGTTTCA-3 and reverse: 5-TCCATATCTTTGATACGACG3), 5 L of 10 PCR reaction buffer (500 mM Tris-HCl, 100 mM KCl, 50 mM (NH4)2SO4, 20 mM MgCl2), 0.2 mM dNTPs, and 1.25 U FastStart Taq DNA polymerase. PCR was programmed for 4 min at 95 C, followed by 40 cycles of 30 s at 95 C, 30 s at 55 C, and 1 min at 72 C, and finalized for 7 min at 72 C. The resulting 1800 bp-long PCR product after the purification using NucleoSpinTM (MachereyNagel, Duren, Germany) was used as a target DNA in this work. Signal location-based DNA detection On a surface capacitive touchscreen system (ESCAP7000, eGALAX_eMPIA technology, Taipei, Taiwan), 1 L of a reference (50 ng/L) and samples A and B of DNA solutions of various concentrations (1 ~ 100 ng/L) were applied at three fixed points. The DNA samples were covered with an ITO-coated cover glass connected with conducting wire. By touching the conducting wire with a finger, the touch signal appears on the display. The length (R) and the angle () from the reference solution point were measured. The equations for the R and as a function of the DNA

concentration of samples were determined by using statistical analysis with MINITAB and MATLAB software. By using the equations, the DNA concentrations of unknown samples were determined. Signal intensity-based DNA detection. On a projected capacitive touchscreen (DM160211, Microchip, Chandler, AZ), six samples (10 L) with various concentrations (9.2 10-4 ~ 9.2 10 ng/L) were applied. The touchscreen controller measures the amount of the capacitance change by counting the charging pulse count number, which is recorded by the supported PCCU (projected capacitive configuration utility) software (http://www.microchip.com/mtouch). With the standard curve of charging pulse count number as a function of the DNA concentration, the DNA concentrations of unknown samples were determined. Absorbance-based DNA quantitation. The concentration of PCR product was determined using Nanodrop ND-1000 (Wilmington, DE) spectrophotometer based on the generally accepted extinction coefficient of double-stranded DNA (50 ngcm/L). Detection of capacitance change of polypyrrole (PPy) conducting polymer The PPy film was formed on a Au electrode (0.28 cm2) using 0.1 M aqueous pyrrole solution in the presence of 0.5 M lithium chloride at 0.7 V (vs Ag/AgCl) for 1 min. After washing, impedance spectra were acquired using a GAMRY Reference 600 (Warminster, PA) in the frequency range of 100 kHz-50 mHz with an alternating voltage of 10 mV at a formal DC potential of 0.4 V for oxidation state and -0.6 V for reduction state of PPy coated on the electrode, respectively. The double layer capacitances of the oxidized (24.8 F) and reduced PPy film (5.1 F) were determined by fitting the experimental data to a model equivalent circuit using GAMRY eChem Analyst software. The PPy film on the touchscreen was formed by chemical oxidation of 0.043 M pyrrole in the presence of 0.1 M FeCl3 for 1 h. The PPy layer formed on the touchscreen was successively reduced and oxidized by 1 h reactions with 2 M NH3 solution and 0.1 M FeCl3, respectively. The capacitance change of the touchscreen represented by the charging pulse count number was measured after each oxidation and reduction step.

Figure S1 Real image of signal location-based DNA detection method utilizing surface capacitive touchscreen (inset: samples between the touchscreen panel and ITO-coated cover glass).

Figure S2 Touch signal locations displayed on the screen, which are recognized by the signal location based method using the surface capacitive touch screen when series of sample sets listed are applied on the fixed points at A and B.

Figure S3 The capacitance represented by the charging pulse count number according to the DNA concentrations of test samples on the projected capacitive touchscreen recorded by the supported projected capacitive configuration utility (PCCU) software. The projected capacitive touchscreen used in this study contains 12 electrodes in x-axis, and the samples were applied onto the electrode number 1, 3, 5, 7, 9, and 11.

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Figure S5 Real image of touchscreen on which the spots of PPy film were coated

2.2For the detection of cancer using Micro-NMR:

We report the first human-based application of this mNMR device, notably for molecular profiling ofcancer cells obtained by fine-needle aspirates from suspected intraabdominal tumors. The system incorporates multiplexed measurement capacity, microfluidic specimen delivery, feedback control for temperature variations, and a user-friendly interface within a 10 cm by 10 cm footprint for clinical bedside operation (Fig. 1). Compared to earlier devices (15, 17 ), DMR-3 is more sensitive and temperaturestable, contains integrated analysis and measurement software, and can be operated through a simple-to-use smart phone application (Fig. 1). After optimization of magnetic affinity ligands, we clinically tested this device on 50 patients with suspected malignancies and then validated our findings in an independent cohort containing an additional 20 patients (n = 70 patients total). To determine whether this new technology could overcome current diagnostic challenges in oncology, we specifically designed the study to address the following questions: What is the diagnostic accuracy of the mNMR technology and how does it compare to 4the current standard of care?

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What is the heterogeneity of marker expression within and across patients? What are the ex vivo properties of recently harvested cancer cells with respect to marker distribution, cellular half-lives, and changes in biomarker profiles over time (18)? Overall, we show that processed samples from single fine-needle aspirates of intra abdominal lesions from human patients with suspected malignancies contain sufficiently high numbers of cells to enable real-time quantitative analysis of many molecular markers. We thus anticipate that this real-time diagnostic technology will have a wide range of applications in oncology and that the approach may be transferable to testing of different markers in other cell types and specimens

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Fig. 1. The mNMR clinical analysis system (DMR-3) and bioconjugation strategy (BOND-2). (Left, top) Complete mNMR system for use at the patients bedside. The bottom component contains all of the circuitry for NMR measurements, whereas the top enclosure holds a permanent magnet and chip-sized microliter-volume sensors. (Left, bottom) Stateof- the-art mNMR probe used for sensing within the mini magnet. (Right, top) Smart phone interface for operating the mNMR system. (Right, bottom) Fineneedle aspirates from each patient sample were processed with a bio-orthogonal amplification strategy adapted for clinical samples. The bio-orthogonal amplification allows ultrasensitive detection of cellular proteins.

3.CONCLUSION
Smartphones equipped with what are essentially hand-held MRI scanners can accurately diagnose life-threatening tumors, researchers say. The miniature scanner could diagnose cancer faster, more accurately and less expensively than the current gold standard technique used in the field. Improvements in diagnosis could lead to matching improvements in therapies, the inventors added. Nuclear magnetic resonance or NMR scanners immerse samples in magnetic fields and then hits them with radio waves, encouraging atoms to emit signals that shed light on the composition of the molecules they are in. NMR was renamed magnetic resonance imaging or MRI in medicine so as to not scare people with the word "nuclear." MRI scanners typically use large, powerful magnets, but that is unnecessary when the samples being scanned are very small say, just one-millionth of a liter of fluid, which is all that is needed for an accurate detection of cancer cells. Researchers now have developed a device "that, even including the magnet, can fit in the palm of your hand". nuclear magnetic resonance (NMR) device uses 0.5 telsa of magnetic energy less powerful than the magnet in a typical loudspeaker. Thus this device helps to detect the cancer with less resources and reduced effects on the body.

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4.REFERENCES
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