WO2021236039A2

WO2021236039A2 - An improved and rapid system for determination of various pathogens

Info

Publication number: WO2021236039A2
Application number: PCT/TR2020/051488
Authority: WO
Inventors: Melih Ballikaya
Original assignee: Smarte Teknoloji Ve Enerji Sanayi Ticaret Anonim Sirketi
Priority date: 2020-05-19
Filing date: 2020-12-31
Publication date: 2021-11-25
Also published as: WO2021236039A3

Abstract

The present invention proposes a system (1) which includes one or more apparatus(es) (100) for label-free detection, identification and/or quantification of patogens. Said system (1) comprises a first conductive plate (20) which is arranged for sweeping a sample (30) at a plurality of predetermined frequencies within the range of from 1 GHz to 64 GHz or in part of the range, the first conductive plate (20) being arranged for emitting a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range and for transmitting the electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range, a second conductive plate (40) which is spaced apart from the first conductive plate (20), the second conductive plate (40) being arranged for receiving and/or collecting electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range, one or more sensor(s) (50) arranged for acquiring spectral information from the sample (30) and generating, based on said spectral information, at least one electrical signal representative of a characteristic of the sample (30), the one or more sensor (50) being capable of detecting a plurality of input signals, output signals, reflected signals, transmitted signals and scattered signals.

Description

AN IMPROVED AND RAPID SYSTEM FOR DETERMINATION OF VARIOUS

PATHOGENS Technical field of the invention

The present invention relates to a system for detection, identification and quantification of various pathogens. It further relates to an apparatus for determination of pathogens based on the measurement of at least one predetermined electrical parameter.

Background of the Invention Testing and rapid detection of pathogens is a crucial issue in the elimination of risks related to health and safety. Classically, a pathogen detection is achieved by isolation and replication of the organism from a normally sterile environment

Many detection methods are based on the presence of the viral genetic material. A virus which is capable of infecting the host must have durable construction, including genetic material. Antimicrobial implementation, such as exposing the virus to heat or disinfectants, prevent the virus from infecting its host. For instance, coronaviruses causing the Covid-19 disease must have an intact genetic material so as to infect its host. Current determination methods and systems for the virus are mostly based on the polymerase chain reaction (PCR) which detects the genetic material of a virus. The kind of methods mentioned above cannot differentiate between an intact virus and a virus which is incapable of infecting its host. Pathogen detection has become one of the most demanding aspects due to the rapid spread of infectious diseases in the community and accordingly inducing significant costs. Therefore, a need exists for effectively providing an easy, convenient, and low-cost per test system for the detection of pathogens. Objects of the Invention

Primary object of the present invention is to provide a determination and identification system and method which features short response time and low cost per test for pathogen detection.

A further object of the present invention is to propose a system which is easy to operate, has long service life and is easy to maintain by having a simple structure.

Still a further object of the present invention is to propose a system which enables remotely changing of the settings in one or more detection apparatusv

Other objects of the present invention will become apparent from accompanied drawings, brief descriptions of which follow in the next section as well as appended claims.

Summary of the Invention

The system proposed by the present invention is durable, has a long service life and does not consume high amounts of energy during use and is therefore economically advantageous in terms of operational costs.

The present invention proposes a system including one or more apparatuses for label-free detection, identification and/or quantification of one or more pathogen(s) in a sample using radio waves. The system is configured to sweep a sample at frequencies in the range of 1 GHz to 64 GHz. In a possible embodiment, the system is configured to sweep periodically and / or continuously sweep a sample at frequencies in the range of 1 GHz to 64 GHz. Said system comprises a first conductive plate which is arranged for continuously sweeping a sample at a plurality of predetermined frequencies within the range of from 1 GHz to 64 GHz or in part of the range, the first conductive plate being arranged for emitting a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range and for transmitting the electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range, a second conductive plate which is spaced apart from the first conductive plate, the second conductive plate being arranged for receiving and/or collecting the electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range, one or more sensor unit(s) which is arranged for acquiring spectral information from the sample and generating, based on said spectral information, at least one electrical signal representative of a characteristic of the sample, the sensor unit being capable of detecting a plurality of input signals, output signals, reflected signals, transmitted signals and scatered signals, a central unit provided with a digital database including at least one digital library of uniquely identifiable information of known pathogens and further including a plurality of spectra and pre-determined signals characteristic of a plurality of pathogens for detection, identification and/or quantification of at least one pathogens in a sample, at least one processor which is in communication with the central processing unit, the processor arranged for determining a characteristic of the target pathogen based upon the absorption characteristics thereof in a frequency range of from 1 GHz to 64 GHz.

In a possible embodiment, the system further comprises at least one inlet port where at least one input signal in a frequency range of from 1 GHz to 64 GHz is introduced to the system and at least one outlet port where at least one output signal is generated.

In a possible embodiment, the sensor unit comprises at least one electrical conductivity sensor, at least one impedance sensor, at least one photo sensor, at least one temperature sensor or a combination of these for providing feedback signals representative of a local frequency and a local temperature to the central unit.

Brief Descriptions of the Drawings

Fig. 1 illustrates a schematic view of the system according to the present invention comprising a first conductive plate and a second conductive plate in accordance with a possible embodiment.

Fig. 2 illustrates a schematic view of the system according to the present invention comprising a first conductive plate, a second conductive plate, a carrier and a plurality of probes in accordance with a possible embodiment.

Fig. 3 illustrates the system including more than one apparatus in accordance with a possible embodiment.

Fig. 4 illustrates an exemplary first conductive plate and second conductive plate in accordance with a possible embodiment.

Fig. 5 illustrates another exemplary first conductive plate and second conductive plate in accordance with a possible embodiment.

Fig. 6 illustrates a flow channel in accordance with a possible embodiment of the invention. Fig. 7 illustrates an exemplary embodiment of the invention arranged as an air conditioner.

Fig. 8 illustrates an exemplary embodiment of the invention comprising a waveguide and a pressurizing means in accordance with a possible embodiment.

Fig. 9 an exemplary embodiment of the invention comprising a microfluidic channel in accordance with a possible embodiment.

Fig. 10 illustrates an exemplary embodiment comprising lap on chip devices having a microscale flow channel in accordance with a possible embodiment.

Fig. 11 illustrates an exemplary working embodiment of the system according to the present application.

Fig. 12 illustrates a frontal view of an exemplary working embodiment depicted in Fig. 11.

Fig. 13 illustrates an exploded perspective view of an exemplary working embodiment depicted in Fig. 11.

Fig. 14 illustrates a sectional view of an exemplary working embodiment comprising a microfluidic channel depicted in Fig. 11.

Fig. 15 illustrates an enlarged view of a microfluidic channel depicted in Fig. 11 channel in accordance with a possible embodiment.

Fig. 16 illustrates an absorbance graph of two types of viruses in accordance with a possible embodiment.

Fig. 17 illustrates another absorbance graph of two types of viruses in accordance with a possible embodiment.

Detailed Description of the Invention hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings which are given solely for the purpose of exemplifying embodiments according to the present invention. The list of reference numerals and letters used in the appended drawings are provided at the end of this section. The present invention proposes a system (1) which includes one or more apparatus(es) (100) for label-free detection, identification and/or quantification of infection agents. The determination of the presence of a pathogen is based on the measurement of a predetermined electrical parameter. The predetermined electrical parameter may be any parameter such as current, voltage, electrical impedance or a combination of these.

Said system (1) comprises a first conductive plate (20) which is arranged for sweeping a sample (30) at a plurality of predetermined frequencies within the range of from 1 GHz to 64 GHz or in part of the range, the first conductive plate (20) being arranged for emitting a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range and for transmitting the electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range, a second conductive plate (40) which is spaced apart from the first conductive plate (20), the second conductive plate (40) being arranged for receiving and/or collecting electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 64 GHz or in part of the range, one or more sensor(s) (50) arranged for acquiring spectral information from the sample (30) and generating, based on said spectral information, at least one electrical signal representative of a characteristic of the sample (30), the one or more sensor (50) being capable of detecting a plurality of input signals, output signals, reflected signals, transmitted signals and scattered signals. Moreover the system (1) further includes a central unit (70) provided with a digital database including at least one digital library of uniquely identifiable information of known pathogens and further including a plurality of spectra and pre-determined signals characteristic of a plurality of pathogens for detection, identification and/or quantification of at least one pathogen in a sample (30) and at least one processor (71) which is in communication with the central unit (70), the processor (71) arranged for determining a characteristic of a target pathogen based upon the absorption characteristics thereof in a frequency range of from 1 GHz to 64 GHz. Furthermore, in a possible embodiment, the central unit (70) may be configured to operate the system at incremental frequencies within a specific frequency range so as to sweep the sample housing (35) at different frequencies.

In a possible embodiment of the invention, a first conductive plate (20) and a second conductive plate (40), respectively, are arranged as a first planar plate (20) and a second planar plate (40) which are exemplified in Fig. 4 and Fig. 5. In a possible embodiment, the system (1) includes an inlet port (60) in electronical communication with the first conductive plate (20) and an outlet port (65) in electronical communication with the second conductive plate (40) as shown in Fig. 1 and Fig. 2. For improved test accuracy, the inlet port (60) comprises at least one sensor (50) arranged for detecting at least one input signal and the outlet port (65) comprises at least one sensor (50) for detecting at least one output signal.

In accordance with said embodiment, when a potential difference is applied on the first conductive plate (20) or when the first conductive plate (20) is coupled to an external source of electricity, an electrical force acts on the electrons of first conductive plate (20), therefore, the electrons begin to move and said motion forms the electrical current. In order to efficiently transmit the electrical current, it is expected that the potential difference required to transmit the current is low; hence the electric current prefers to pass through conductive plates with low resistivity. If an electrical charge differential is created between the first conductive plate (20) and the second conductive plate (40), a gap therebetween prevents the transmission of electric current. Providing that a sample (30) including at least one pathogen or a medium with higher conductivity is placed in the gap so as to be in physical contact with the first conductive plate (20) and the second conductive plate (40), the electric current is transmitted to the second conductive plate (40) passing through the sample (30) or medium which comprises the target pathogen or a group of pathogens. In a possible embodiment, a medium arranged between conductive plates has a relative permittivity less than the sample (30) to be detected.

In a possible embodiment, one or more apparatus (100) further comprises a sample housing (35) which is arranged between the first conductive plate (20) and the second conductive plate (40). Optionally, the sample housing (35) has two ends, a first end (31) facing the first conductive plate (20) and a second end (33) facing the second conductive plate (40).

Frequencies characteristic of a pathogen (e.g. a virus) may depend on the absorption or radiation characteristics; therefore, the range of frequencies to be employed may vary in the presence of different kinds of pathogens in the sample (30).

In a possible embodiment, the gap between the first conductive plate (20) and the second conductive plate (40), which accommodates the sample housing (35), is configured as an aperture wherein said aperture has a dimension less than a target pathogen or a specified group of the pathogen. Flence, the pathogen can match with said aperture, and accordingly, the electrical current can flow through. If the gap between the first conductive plate (20) and the second conductive plate (40) is larger than the dimension of the pathogen, the electric current cannot be measured at the outlet port (65), since the electrical current cannot pass through the gap. In such cases, the measurement can be taken by placing the pathogen in a connection medium or a carrier (34), provided that the dimension of the conductive medium or carrier (34) to be employed must be equal to or greater than the gap between the first conductive plate (20) and the second conductive plate (40).

Referring to Fig. 2, owing to the smaller size of the pathogen, pathogen determination may occur in the presence of a connection medium since the detection of pathogen is based on the relationship of the electrical power differences measured at the inlet port (60) and the outlet port (65) and on the pathogen's absorption of the energy. Initially, the absorption of the connection medium shall be calculated. The measurement of the first electrical parameter is then analyzed in order to determine the electrical characteristics of the connection medium wherein the first electrical parameter may be any parameter selected from the group consisting of current, voltage and electrical impedance. The second step is placing a pathogen/or a group of pathogens in the connection medium. Thereafter, application of electrical current is carried out and the predetermined electrical parameter is measured. The difference between said two measurements are analyzed since this difference is observed owing to the presence of at least one pathogen. A sensor unit (57) employed in said exemplary embodiments includes one or more sensors (50) and said sensor (50) may be an electrical conductivity probe or an impedance probe or a photo sensor (50).

In a possible embodiment, the apparatus (100) may comprise at least one carrier (34) whose electrical properties are recorded in the database of the central unit (70). Said carrier (34), optionally, comprises a slot (32) for accommodating a predetermined amount of the sample (30). The electric current transmitted to the first conductive plate (20) reaches the carrier (34) disposed on the sample housing (35) and the electric current is transferred to the second conductive plate (40) by passing through the slot (32) where the sample (30) is accommodated, after advancing a specified distance in the carrier (34). Optionally, in order to prevent contamination of the apparatus (100), the sample (30) containing the pathogen is placed on a disposable carrier (34) and the measurement is implemented, in such a case, the analysis is complicated taking into account the response of the carrier (34) to the electrical current. Within this scope, only the carrier (34) is positioned at the sample housing (35) (i.e. without a target pathogen or a group of pathogens) and the measurement is carried out within the predetermined frequency range. Thereafter, the sample (30) containing the pathogen is applied on the carrier (34) and the measurement is conducted under the same conditions and the central unit (70) reports the output of the measurement. The data from the two measurements are processed by the processor (71) in the central unit (70) and at least one spectrum corresponding to the difference between the said data is made of record.

SUBSTITUTE SHEETS (RULE 26) The exemplary embodiments of the system (1) including two apparatus (100) is illustrated in Fig. 3. This system (1) that is beneficial for detecting the pathogen in samples (30) containing complex matrices includes a plurality of electrical conductivity probes arranged in sensor unit (57). Said sensor unit (57) includes the following list of probes: The first electrical conductivity probe (51) is configured to measure the electrical current entering the first conductivity plate (20), the second electrical conductivity probe (52) is configured to measure the electrical current at the first end (31) of the sample housing (35) facing the first conductive plate (20), the third electrical conductivity probe (53) and the fourth electrical conductivity probe (54) are configured to measure the electric current in the regions where the sample (30) contacts the connection medium, the fifth electrical conductivity probe (55) is configured to measure the electrical current exiting the sample housing (35) and the sixth electrical conductivity probe (56) is configured to measure the electrical current at the output port (65). For more accurate analysis, several conductivity probes can be attached to the system (1) in this embodiment.

In a possible embodiment, the pathogen may be cultivated in a nutrient medium with higher conductivity than the carrier (34). In this case, measurements are conducted simultaneously in the system (1) including two apparatuses (100) with identical features connected to the central unit (70) as exemplified in Fig. 3. The carrier (34) and medium are placed in the sample housing (35) of the first apparatus (100) whereas the medium having pathogens and the carrier (34) are placed in the sample housing (35) of the second apparatus (100). The central unit (70) analyses the measurements taken from the two apparatuses (100) and evaluates the differences thereof. As a result of this comparison, the presence of the pathogen corresponding to the formation of the difference is detected.

In a possible embodiment, the system (1) further comprises an impedance sensor (50), where the impedance sensor (50) is configured to measure a low-frequency and a high-frequency impedance, an impedance analyzer, where the impedance analyzer is coupled to the impedance sensor (50) and a low voltage power.

In accordance with the possible embodiment, the sensor unit (57) may include more than one temperature probes which are in communication with the central unit (70) and the processor (71) such that both can analyse the data provided by the temperature probe and revise the frequency spectrum. Various mediums containing pathogens demonstrate absorption losses through electrical conduction under microwave irradiation. Dielectric losses of the majority of solids are often affected by temperatures. Hence, measurement changes in temperature throughout the process plays a key role in the determination of pathogens with high accuracy

SUBSTITUTE SHEETS (RULE 26) and precision can be ensured. In a possible embodiment, the temperature probe and the electrical conductivity probe may be arranged on the same probe element.

In a possible embodiment more than one sensors (50) are configured as an electrical conductivity probe, an impedance probe, a temperature probe, a humidity probe, a fluid quality probe or a combination of these. The system (1) further comprises a plurality of sensors (50) wherein respective ones of the plurality of sensors (50) operates over different ranges of frequencies. Detection time is reduced by employing multiple probes.

In a possible embodiment, the first conductive plate (20) is arranged as an emitting connector and/or antenna (26) which is capable of emitting a radio frequency within the range of lGHz and 40 GHz and a second conductive plate (40) is arranged as a receiving connector and/or antenna (26) which is capable of collecting radio frequency within the range of lGHz and 40 GHz for receiving electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 40 GHz. In accordance with this embodiment, the source of electromagnetic energy may take the form of any suitable frequency oscillator, such as a voltage-controlled oscillator (VCO) (4), a dielectric resonator oscillator (DRO) (13), a surface acoustic wave (SAW) oscillator, a frequency multiplier or a Gunn diode oscillator.

In a possible embodiment, the first conductive plate (20) may be formed as a first antenna (26) configured to emit electromagnetic energy at predetermined frequencies within a range of about 1 GHz to about 40 GHz, corresponding to absorption frequencies associated with the pathogen. The second conductive plate (40) may be formed as a second antenna (26) which is adapted to receive unabsorbed energy from a pathogen and which generate a plurality of signal defining the unabsorbed energy. Moreover, the antennas (26) or the first conductive plate (20) and the second conductive plate (40) are operable, with sufficiently broad frequency response, to sweep the sample housing (35) at different frequencies in a specific range or specific ranges. In accordance with a possible embodiment of the invention, waves in appropriate range applied to the sample (30) having a pathogen can be absorbed, scattered, transmitted and/or reflected and then said transmitted and/or scattered waves can be detected and/or recorded. The central unit (70) can be configured and is operable to construct a curve from peaks of at least one of a transmitted spectra, a reflected spectra and an absorbed spectra to develop a wideband curve or profile over at least one of the microwave bands.

In accordance with a possible embodiment of the invention, the central unit (70) may comprise algorithms which reactively tune to at least one of specifically predesignated absorption frequencies or transmittance frequencies and provide a specific frequency and/or amplitude

SUBSTITUTE SHEETS (RULE 26) modulation parameter associated with a known pathogen that exists in a database. Moreover the central unit (70) further comprises a database including the characteristic frequency of a plurality of different pathogens. In accordance with a possible embodiment of the invention, the processor (71) may be configured to process the magnitude of the electromagnetic wave and convert it into a form that provides useful information regarding kinds of pathogens. Obtained processed data may be sent to a remote station (73). Moreover; the processor (71) for converting said changes in magnitude can be used to represent information regarding pathogens and present said information to an end-user through a display unit (83), said information including the concentration of contamination wherein said display unit (83) can generate at least one visual and audible signal indicating a threshold degree of the pathogen contamination.

The processor (71) may be programmed to determine parameters of the pathogen and/or medium in response to the respective output signal produced by each of the plurality of detector (50). Said processor (71) is arranged for comparing phases of at least one of the absorbed and transmitted electromagnetic energy. Said processor (71) is provided with a digital database of a plurality of wavelength data corresponding to said wavelength settings for remotely imposing one or more of said wavelength settings to said system (1).

In accordance with a possible embodiment of the invention, the system (1) further comprises an amplifier configured to amplify the detected signal; and a modulator coupled to the amplifier and configured to down-shift/up-shift the amplified signal. Hence pathogens can be accurately detected and quantified with high sensitivity and selectivity.

In another optional exemplary embodiment, antennas (26) may be connected to a switching unit. The switching unit can, in turn, be connected to both a transmitting channel and a receiving channel. The switching unit selectively couples each of the conductive plates to either the transmitting channel or the receiving channel. The transmitting channel comprises a synthesizer, alternatively a signal generator (10) and an amplifier. The receiving channel includes an amplifier coupled to a central unit (70).

In an optional embodiment, the system (1) further comprises a computer-readable storage medium for detection of pathogens in a media or in a fluid wherein the computer-readable storage medium provides instructions to command the central unit (70).

In a possible embodiment, the invention proposes a method based on determining the electrical measurements of pathogens and measuring the electrical properties of a targeted

SUBSTITUTE SHEETS (RULE 26) pathogen and/or evaluation of viral load in a sample (30). Said method mainly comprises placing a pathogen or pathogen included sample (30) in an electrically conductive medium; applying a predetermined voltage or a predetermined electrical current across the pathogen or pathogen included sample (30), detecting electrical current through the first conductive plate (20) and second conductive plate (40), comparing the detected electrical current across the pathogen, and matching the same with the data provided in the central unit (70), thereby determining the type of pathogen.

In another possible embodiment, the present invention provides a method comprising the steps of, sweeping the spectrum over a broad range of frequencies, obtaining a plurality of radio frequency responses of pathogen deposited within the sample (30), transmitting a signal over a first range of frequencies to the sample (30), detecting at least one parameter of the radio frequency response and identifying a type of the virus based on a comparison between the RF input value and RF output value.

In accordance with the possible embodiment of the present invention, when the sample (30) is in the form of a flowing fluid, the sample housing (35) is configured as a channel. Referring to Fig. 6, the gap between the first conductive plate (20) and the second conductive plate (40) is configured as a flow channel (38) to allow the passage of the fluids in a continuous flow wherein said flow channel (38) spans the distance between the first conductive plate (20) and the second conductive plate (40). The sample (30) can be in the form of a gas such as air or a liquid such as water. For instance, as illustrated in Fig. 7, the apparatus (100) may be arranged for engaging with a fluid flow port (82), thereby being arranged for forming a fluid passage to a fluid when streaming through such fluid flow port (82).

Referring again to the embodiment illustrated in Fig. 7, where the fluid is a gas, e.g. air, for providing a continuous fluid flow, the fluid flow port (82) can be a vent in fluid communication with a pressurizing means (81) such as a fan of an air conditioning unit or an air purification device. In accordance with this embodiment, in the case where the sample (30) is air, the system (1) further comprises one or more fluid quality sensor(s) (50) which can be arranged to detect the status related to or more of airborne particles (e.g. PM2.5), or volatile organic compounds (VOCs) or carbon dioxide.

Fig. 8 is a schematic depiction of an integrated system (1) comprising an air conditioning device and one or more apparatus(es) (100). In accordance with said exemplary embodiment, the system (1) further comprises a power supply for fulfillment of power requirements of the system (1), a memory unit (74) in communication with a signal generator (10) and a communication unit (72) having a user interface unit operably coupled to said central unit (70)

SUBSTITUTE SHEETS (RULE 26) that permits the user to integrate the information and control intensity of the energy generation.

As an optional embodiment, said system (1) can be easily integrated into an automated system whereby the condition of airflow is monitored and reported regularly by instrumentation. The system (1) in accordance with this embodiment both the inlet port (60) and the outlet port (65) comprise more than one sensors (50) which may comprise an electrical conductivity sensor (50), a fluid quality sensor (50), a temperature sensor (50), a photo sensor (50) or a combination of these. By processing the data obtained from the said sensors (50) in the central unit (70), the type of pathogen in the fluid can be detected. Optionally, the processor (71) is arranged to obtain one or more data set(s) for the electrical signals which are produced during the flow of the fluid along the flow channel (38). The system (1), which is capable of rapid pathogen detection, is applicable in assessing the air quality of the environments in which people work or live together.

In accordance with a possible embodiment, as illustrated in Fig. 10 to Fig. 14, the system (1) may comprise a first chamber (86), a second chamber (87), a third chamber, more than one filters (89) such as metal sintered filters (89), a pressurizing means (81) arranged between the second camber (87) and the third chamber (88), and a microfluidic channel (47) adapted to receive a flow containing a plurality of pathogens in a sample (30), i.e. flowing fluid. The microfluidic channel (47) includes a detection area (48) where the first conductive plate (20) and the second conductive plate (40) are adapted to apply an electrical field across the detection area (48). In a possible embodiment, the microfluidic channel (47) is capable of hydrodynamically centering the flow of a plurality of pathogens through the detection area (48) as shown in Fig.15. Hence, effective detection and identification of a target pathogen are provided. As again illustrated in Fig. (9), the system (1) comprises one or more collecting chamber(s) (46) in fluid communication with the microfluidic channel (47). The processor (71) of said system (1) is configured as a microprocessor, a digital signal processor or a microcontroller. Said apparatus (100) further comprises at least one micro water chamber (45) and a microfluidic flow controller, hence said apparatus (100) provides enhanced determination of pathogens via droplet-based microfluidic arrangement. Furthermore, said microfluidic channel (47) comprises a pressurizing means (81) configured to impose a differential pressure between the entrance and exit of the microfluidic channel (47) for perfusing the sample (30) in the form of a flowing fluid and for tuning the flow rate thereof.

In a possible embodiment, a sample (30) including a virus is loaded on the sample housing (35) and waves in the appropriate range are emitted. The apparatus (100) having a microfluidic channel (47) further comprises commercially available and low cost waveguides

SUBSTITUTE SHEETS (RULE 26) (25) (such as WR90), an inlet port (60) at a first end of the waveguide (25) configured to allow electromagnetic energy that creates a radio frequency; an output port (65) at a second end (33) of the waveguide (25) configured to allow microwave energy to exit the waveguide (25) microwave cavity. More than one sensors (50) measure the transmittance and frequency change of the electromagnetic waves passing through the sample (30), hence the central unit (70) can specify type of virus or viruses.

An exemplary working embodiment in accordance with the invention is depicted in Fig. 10. Said apparatus (100) comprises a first antenna (26), a second antenna (26), a ground plane (90) which allows the antennas (26) to be mounted, more than one sensors (50) for provision of feedback about a local frequency and power status inside the apparatus (100), a cover (84), a holding plate (85) having a size and shape suitable to receive a collecting chamber (46) wherein said collecting chamber (46) is provided with a plurality of passage openings (49) which are arranged in line with each other along the perimeter of the collecting chamber (46) for receiving flowing fluid into the apparatus (100). Moreover, said system (1) may comprise a battery unit for rendering a portable device. Said system (1) provides improved speed and quality in monitoring in microbial risk assessment.

Fig. 16 demonstrates an absorbance spectra of the exemplary working embodiments in accordance with the invention comprising the absorbance of the measurement of M13 phage which is a long-rod shape bacterial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is observed that the Rod shape (M13) and SARS-CoV-2 presents distinctive absorbance spectra where the first line represents the M 13 phage absorbance pattern whereas the dashed line represents (SARS-CoV-2) absorbance pattern. Similarly, the applied stimulation signals can have predetermined frequencies attuned to a specific pathogen. For example, MS2 and Influenza have a distinguishable response (e.g., complex impedance, resistance, etc.) with respect to a selected frequency. For instance, applying signals with a frequency range between 1 GHz to 40 GHz to the sample (30) can distinguish the MS2 virus from the Influenza as depicted in Fig. 17.

In a possible embodiment, the system (1) is configured as an integrated system (1). The system (1) having more than one apparatus (100), is arranged for performing pathogen detection based on the consistency between the permittivity frequency spectrum of a receiver signal and the conductivity frequency spectrum of a receiver signal amplitude of a given spacing for achieving accurate and reliable determination of pathogens. The central unit (70) of said system (1) is arranged for processing, simultaneously, the frequency-dependent conductivity parameter and frequency-dependent permittivity parameter. Said system (1) can be adapted to determine the pathogens in a blood sample (30). The ingredient of human blood

SUBSTITUTE SHEETS (RULE 26) is not constant and this instability affects dielectric properties thereof. An infected tissue has a different electrical conductivity and electromagnetic permittivity compared to an uninfected tissue. The amount of energy absorbed by the tissue is a function of the dielectric properties, the system (1) has a database comprising preliminary results having the absorption characteristic of common blood ingredients in a specified range, hence sensitive measurement of dielectric parameters is employed to distinguish between normal and infected blood sample (30). Therefore, sensitive detection of a pathogen in a blood sample (30) is achieved with a minimum amount of blood sample (30). Reference list 1 system

10 signal generator 20 first conductive plate 25 waveguide 26 antenna

30 sample

31 first end

32 slot

33 second end 34 carrier

35 sample housing 38 flow channel 40 second conductive plate

45 micro water chamber 46 collecting chamber

47 microfluidic channel

49 passage opening

50 sensor

51 first electrical conductivity probe 52 second electrical conductivity probe

53 third electrical conductivity probe

54 fourth electrical conductivity probe

55 fifth electrical conductivity probe

56 sixth electrical conductivity probe 57 sensor unit

60 inlet port 65 outlet port 70 central unit

SUBSTITUTE SHEETS (RULE 26) 71 processor

72 communication unit

73 remote station

74 memory unit 81 pressurizing means

82 fluid flow port

83 display unit

84 cover

85 holding plate 86 first chamber

87 second chamber

88 third chamber

89 filter

90 ground plane 100 apparatus

Claims

1. A system (1) including one or more apparatus (100) for label-free detection, identification and/or quantification of one or more pathogen(s) in a sample (30) using radio waves; comprising:

- a first conductive plate (20) which is arranged for sweeping a sample (30) at a plurality of predetermined frequencies within the range of from 1 GHz to 64 GHz or in part of the range, the first conductive plate (20) being arranged for emitting a plurality of frequencies within the range of from 1 GHz to 64 GHz and for transmitting the electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 64 GHz,

- a second conductive plate (40) which is spaced apart from the first conductive plate (20), the second conductive plate (40) being arranged for receiving and/or collecting the electromagnetic energy at a plurality of frequencies within the range of from 1 GHz to 64 GHz, one or more sensors (50) which is arranged for acquiring spectral information from a sample (30) and generating, based on said spectral information, at least one electrical signal representative of a characteristic of the sample (30),

- a sensor unit (57), having said one or more sensors (50), capable of detecting a plurality of input signals, output signals, reflected signals, transmitted signals and scattered signals,

- a central unit (70) provided with a digital database including at least one digital library of uniquely identifiable information of known pathogens and further including a plurality of spectra and pre-determined signal characteristics of a plurality of pathogens for detection, identification and/or quantification of at least one pathogens in the sample (30), at least one processor (71) which is in communication with the central unit (70), the processor (71) arranged for determining a characteristic of a target pathogen based upon the absorption characteristics thereof in a frequency range of from 1 GHz to 64 GHz.

2. The system (1) according to the Claim 1, further comprising at least one inlet port (60) where at least one input signal in a frequency range of 1 GHz to 64 GHz is introduced to the system (1) and at least one outlet port (65) where at least one output signal is generated by the system (1).

SUBSTITUTE SHEETS (RULE 26)

3. The system (1) according to the Claim 2, wherein the inlet port (60) which is electronically in communication with the first conductive plate (20) comprises at least one sensor (50) arranged for detecting at least one input signal and the outlet port (65) which is electronically in communication with the second conductive plate (40) comprises at least one sensor (50) for detecting at least one output signal.

4. The system (1) according to any of the preceding claims, wherein the processor (71) is arranged for analysing the data provided by said at least one sensor (50), producing a spectrum based on detected data, correlating the frequency spectrum with a plurality of spectra and predetermined characteristic signals of at least one pathogen.

5. The system (1) according to any of the preceding claims wherein the sensor unit (57) comprises at least one electrical conductivity sensor (50), at least one impedance sensor (50), at least one photo sensor (50), at least one temperature sensor (50) or a combination thereof for providing feedbacks representative of a local frequency and a local temperature.

6. The system (1) according to any of the preceding claims, wherein the first conductive plate (20) is arranged as an emitting connector and/or antenna (26) which is capable of emitting a radio frequency within the range of lGHz and 40 GHz and a second conductive plate (40) arranged as a receiving connector and/or antenna (26) which is capable of collecting radio frequency within the range of lGHz and 40 GHz for receiving electromagnetic energy at a plurality of frequencies within the range of 1 GHz to 60 GHz.

7. The system (1) according to any of the preceding claims wherein one or more apparatus (100) further comprises a sample housing (35) which is arranged between the first conductive plate (20) and the second conductive plate (40).

8. The system (1) according to Claim 7, further comprising one or more collecting chambers (46) in fluid communication with the sample housing (35) and the collecting chamber (46) comprises a plurality of passage openings (49) which are arranged in line with each other along the perimeter thereof for receiving the sample (30) into the system (1).

9. The system (1) according to Claim 7 wherein the sample housing (35) is a flow channel (38) arranged for passage of the fluids.

10. The system (1) according to any of the preceding claims, said system further comprising a microfluidic channel (47) wherein said microfluidic channel (47) comprises a pressurizing means (81) configured to impose a differential pressure between the entrance and exit of the microfluidic channel (47) for perfusing a sample (30) in the form of a flowing fluid and for tuning the flow rate.

11. The system (1) according to any of the Claim 7 to Claim 10, further comprising one or more collecting chambers (46) in fluid communication with the sample housing (35) for providing a continuous fluid flow.

12. The system (1) according to any of the preceding claims, wherein the system (1) is adapted to engage with a fluid flow port (82) of an air conditioning system for providing continuous determination of pathogens in the airflow and the microbial monitoring of local air quality.

13. The system (1) according to any of the preceding claims, wherein the system (1) is arranged as a portable device which comprises a battery unit.

14. The system (1) according to any of the preceding claims, wherein the system (1) is arranged as a lab-on-a-chip device.

15. The system (1) according to any of the preceding claims, wherein the system (1) is configured as an integrated system (1) having two apparatus (100) wherein one of the apparatus (100) is configured to perform pathogen detection by the measurement of the permittivity frequency spectrum of a plurality of receiver signals; the other apparatus (100) is configured to perform pathogen detection by the measurement of the conductivity frequency spectrum of a plurality of receiver signals and the central unit (70) is arranged for processing, simultaneously, the frequency-dependent conductivity parameter and frequency-dependent permittivity parameter.